Discoveries Fall 2021 by Cedars-Sinai Discoveries magazine

Cedars-Sinai • Fall 2021

FOLLOWING THEIR

HEARTS PEOPLE BORN WITH CONGENITAL HEART DISEASE ARE LIVING LONGER THAN EVER— AS LONG AS THEY DON’T SKIP OUT ON CARE. HOW CAN PHYSICIANS KEEP THEM CONNECTED OVER A LIFETIME?

PLUS HOW TO THINK LIKE A SCIENTIST P. 24 WHEN CANCER AND THE PANDEMIC COLLIDE P. 40

Cedars-Sinai

EXECUTIVE VICE PRESIDENT AND DEAN OF MEDICAL FACULTY Shlomo Melmed, MB, ChB SENIOR VICE PRESIDENT AND CHIEF ADVANCEMENT OFFICER Arthur J. Ochoa, JD VICE PRESIDENT, MARKETING AND COMMUNICATIONS Pattie Cuen EXECUTIVE DIRECTOR, BRAND STRATEGY AND CREATIVE SERVICES Jennifer Fagen EDITOR IN CHIEF Laura Grunberger SENIOR EDITOR Sarah Spivack LaRosa MANAGING EDITOR Susan L. Wampler ASSOCIATE EDITOR Cassie Tomlin DESIGN B&G Design Studios, bgdesignstudios.com STAFF WRITERS Nicole Levine, Victoria Pelham, Rosanna Turner CONTRIBUTING WRITER Carrie St. Michel CEDARS-SINAI DISCOVERIES

© 2021 by Cedars-Sinai. All rights reserved. Reproduction or use in whole or in part without written permission is prohibited. Cedars-Sinai Discoveries is a semiannual magazine produced by Cedars-Sinai’s Advancement Department. Please email questions, comments or requests for more information to: groupeditorial@cshs.org.

To unsubscribe, email unsubscribe@cshs.org or call 323-866-7905. Please provide the code that appears above your name, your full name as listed on the mailing, your mailing address, email, title of piece received and request type (unsubscribe from all Cedars-Sinai mailings or only Discoveries). MAIL:

Senior Editor Cedars-Sinai Discoveries 6500 Wilshire Blvd., Ste. 1900 Los Angeles, CA 90048 EMAIL: groupeditorial@cshs.org Visit us online at cedars-sinai.org/discoveries. For more information about Cedars-Sinai, visit cedars-sinai.org. This publication is for informational purposes only and should not be relied upon as medical advice. It has not been designed to replace a physician’s medical assessment and medical judgment. Always consult first with your physician regarding anything related to your personal health.

ABOUT CEDARS-SINAI

CEDARS-SINAI MAINTAINS THE

Cedars-Sinai is a national leader in providing high-quality, patient-centered healthcare encompassing primary care as well as specialized medicine and conducting research that leads to lifesaving discoveries and innovations. Since its beginning in 1902, Cedars-Sinai has evolved to meet the healthcare needs of one of the most diverse regions in the nation, continually setting new standards in quality and innovation in patient care, research, teaching and community service. Today, Cedars-Sinai is widely known for its national leadership in transforming healthcare for the benefit of patients. Cedars-Sinai impacts the future of healthcare globally by developing new approaches to treatment and educating tomorrow’s physicians and other health professionals. Cedars-Sinai demonstrates a longstanding commitment to strengthening the Los Angeles community through wide-ranging programs that improve the health of its most vulnerable residents.

FOLLOWING GOALS FOR BIOMEDICAL RESEARCH:

• Sustain a program of outstanding biomedical research, healthcare services and nursing research by fostering basic and clinical investigation in the prevention and causes of medical illnesses, their pathologic mechanisms and diagnoses, and the development of cures for the ailments that afflict our society • Translate research discoveries appropriately to a clinical setting • Provide research training opportunities for graduate students and professional teaching programs • Foster the transition of biomedical discoveries to the realms of product development, patient care application and marketing • Provide cross-fertilization and interdependent synergy between the medical center and the biotechnology industry • Protect the rights of human and animal subjects

Cedars-Sinai is fully accredited by the Association for the Accreditation of Human Research Protection Programs Inc. (AAHRPP) for assuring protection for human subjects during research. Cedars-Sinai was the first institution in California to receive this designation. AAHRPP is a Washington, D.C.-based nonprofit organization that uses a voluntary, peer-driven educational model to accredit institutions engaged in research involving human subjects. Cedars-Sinai does not discriminate against any person on the basis of race, color, national origin, disability, age or sex in admission, treatment or participation in its programs, services and activities, or in employment. For further information about this policy, contact the public civil rights coordinator, at 310-423-7972.

FALL 2021

Contents

In This Issue

40 Alone Together

Max Gerber

Physical distancing made it difficult for patients like Kaelyn Garvine to seek comfort and support from friends and neighbors, but like many patients with cancer, she emerged from the pandemic with a new perspective and new connections.

You’ve read about our research. Now learn with us. Our accredited graduate programs prepare you for the future of healthcare. Cedars-Sinai’s Graduate School of Biomedical Sciences is led by some of the nation’s best physicianeducators. We are at the forefront of medicine and innovation, translating groundbreaking discoveries into successful treatments with global impact. Get unparalleled training from a team of research and clinical mentors while working within one of our cutting-edge centers of medical excellence, using next-generation technology and equipment. Cedars-Sinai currently offers three accredited graduate degree programs: • PhD in Biomedical Sciences — Our NIH-supported PhD program merges scientific and translational medicine curricula with mentoring to provide students with a broad exposure to translational research in clinically relevant areas. Open to local, national and international postgraduate candidates who desire to learn from global experts. • Master’s Degree in Health Delivery Science (MHDS) — A program designed to educate ambitious professionals within the healthcare industry about the principles of health delivery science, novel healthcare delivery models and digital health interventions, preparing them to lead meaningful change that results in high-value care delivery. • Master’s Degree in Magnetic Resonance in Medicine (MSMRM) — A 20-month program focused on training graduate students in the field of magnetic resonance imaging (MRI) and various clinical and research applications, including artificial intelligence/deep learning. Open to local, national and international postgraduate candidates who desire to learn from global experts. Cedars-Sinai values community, diversity, organizational integrity and cultural individuality. Our graduate degree programs attract applicants from a wide range of cultural and ethnic backgrounds, giving them an exceptional education in medical and clinical research and imaging technologies.

Learn more and apply today: cedars-sinai.org/graduateprograms

Contents Departments 5 NEWS & NOTES Updated threshold of blood pressure risk in women; understanding genetic variants to improve treatment for inflammatory bowel disease; how a new device could lead to earlier Alzheimer’s diagnosis; honing residents’ skills through robotic-assisted surgery simulators; neuron revelations that could help treat movement disorders; boosting COVID-19 vaccine acceptance rates; how the lack of a flu season in 2020 could affect vaccine efficacy this year; and more

18 MEET LIFE TO THE FULLEST Transplant surgery trailblazer Irene Kim, MD, shares what energizes her, her vision for the Comprehensive Transplant Center she co-directs, and how she finds balance between her personal and professional responsibilities.

20 LEARN TRADING PLACES The challenges of the pandemic have demanded that healthcare providers flex all their clinical muscles—sometimes changing jobs to meet the needs of patients and the community.

22 THINK THREE BIG QUESTIONS ABOUT ‘LONG COVID’ Investigators studying the disease outline the mysteries they’re trying to solve about the lingering and sometimes incapacitating impact of “long COVID.”

45 FACULTY NEWS How a master’s student applied her Hollywood storytelling abilities to the study of Reiki and its impact on hospital patients; awards and grants

48 A LOOK BACK Holocaust survivor and surgical legend George Berci, MD, celebrates a century of pioneering achievement.

Features 24 How to Think Like a Scientist What are the practices and mindsets that help drive great science? Discoveries asked Cedars-Sinai researchers and experts to weigh in about the processes scientists use to shape their work and drive progress.

34 Following Their Hearts People born with congenital heart disease are living longer than ever—as long as they don’t skip out on care. How can physicians keep them connected over a lifetime? COVER Eddie Guy

FALL 2021 | DISCOVERIES |

From the Dean

Our Collective Commitment

“The goal of such painstaking and dedicated efforts is to better understand disease and human health, discover new therapies and, ultimately, improve lives.”

atients, physicians and biomedical scientists from the world over seek out Cedars-Sinai. The attraction of our institution—whether for treatment, medical discovery, postgraduate training or collaboration—is a constellation of devoted, astute minds hard at work solving medicine’s greatest questions. Such experts shine brightly at the Smidt Heart Institute, which was recently ranked #1 in California for cardiology and heart surgery by U.S. News and World Report. Smidt Heart Institute leaders continue to build on a decades-long legacy of pioneering cardiac care at Cedars-Sinai, dating back to 1924, when the medical center installed the first electrocardiogram machine in Los Angeles. Today, the success of the heart institute reflects the fusion of breakthrough translational science and excellence in clinical care. Our research teams are constantly evaluating the effectiveness and safety of novel surgical technologies, ensuring that each patient undergoes the most up-to-date and appropriate procedure for the best outcome. Our teams are also pioneering nonsurgical approaches to valve repair and carefully assessing which patients will most benefit from novel, far less invasive techniques. Our cardiology investigators are developing new methods and tools for predicting and preventing the tragic phenomenon of sudden cardiac arrest, uncovering causes of heart muscle dysfunction that lead to cardiac failure and exploiting these findings to discover new therapies for patients with disordered heart function. Smidt Heart Institute leaders also continue to advance medicine through the innovative technological approaches being developed at the Guerin Family Congenital Heart Program, which is featured in the cover story of this issue of Discoveries. The program’s dedicated, multipronged team is committed to the forward-thinking goal of comprehensive, longitudinal care for all patients with congenital heart defects. From babies still in the womb to octogenarians, the program is improving lives by repairing defective hearts and blood vessels. Dedicated, highly trained scientists and physicians can be found throughout our research enterprise. Though they are each laser-focused on a specific discipline, they are collectively committed to fighting disease and helping people achieve optimal health. In this issue, you will hear from a select group of accomplished investigators who eloquently explain the nuances, complexities and challenges of the scientific process. The goal of such painstaking efforts is to better understand disease and human health, discover new therapies and, ultimately, improve lives. All of this work is done for our patients and for generations of patients to come. Thank you for your continued trust and support.

Shlomo Melmed, MB, ChB

EXECUTIVE VICE PRESIDENT, ACADEMIC AFFAIRS DEAN OF THE MEDICAL FACULTY HELENE A. AND PHILIP E. HIXON DISTINGUISHED CHAIR IN INVESTIGATIVE MEDICINE

| CEDARS-SINAI.ORG/DISCOVERIES

News & Notes Fall 2021

6 STATS | 10 TECH CORNER | 14 COVID-19 RESEARCH | 16 WHO'S WHO

John Kuczala

Something Fishy Although fish oil may have health benefits, Cedars-Sinai research suggests that neither consuming fish oil for omega-3 fatty acids nor taking vitamin D supplements has any effect in forestalling one of the most common and dangerous heart conditions: atrial fibrillation (AFib). The discovery stems from a clinical trial involving more than 25,000 men and women from across the nation. Participants were randomly assigned a regimen of vitamin D, fish oil supplements or a placebo. During a more than five-year period, 3.6% were diagnosed with AFib. Receiving placebos or the real thing made no statistical difference. The trial results do not support taking fish oil or vitamin D supplements to prevent AFib. However, the supplements did not elevate the risk of the condition. The abnormal rhythms of AFib cause the heart to contract irregularly—sometimes too quickly. Nearly 33 million people worldwide have the condition, which can lead to stroke and heart failure. But while fish oil and vitamin D do not help, other preventive measures might. Lifestyle modifications such as maintaining a healthy weight, controlling blood pressure and moderating alcohol intake may lower the risk of AFib. And you can't go wrong reaching for a fishy snack like sardines—the omega-3 fatty acids found in fish reduce overall heart disease risk. FALL 2021 | DISCOVERIES |

N&N

Under Pressure Women have a lower range of ‘normal’ blood pressure than men Cheng, MD, MPH, MMSc, director of the Institute for Research on Healthy Aging at the Smidt Heart Institute and director of Cardiovascular Population Sciences at the Barbra Streisand Women’s Heart Center. Cheng and her research team compared women to women and men to men, rather than the common model of comparing women to men. After examining the blood pressure measurements of more than 27,000 participants across four different studies, 54% of whom were women, they found that systolic pressure levels higher than 110 mmHg in women were associated with risks of heart disease and stroke. “Based on our research

results, we recommend that the medical community reassess blood pressure guidelines that do not account for sex differences,” says Cheng, who

STATS: THE RIGHT TO BE CHILD-FREE Female sterilization—a permanent procedure on the fallopian tubes to prevent pregnancy—is the most common form of contraception worldwide. Despite its popularity, women can find themselves dissuaded from the procedure by physicians who caution that their patient might change her mind or disappoint a future partner. “It’s pure paternalism,” says Natasha Schimmoeller, MD, a gynecologist in Cedars-Sinai’s Family Planning Program. “The notion of female sterilization and regret are inappropriately paired.” Schimmoeller is committed to providing “child-free-friendly” gynecology to women at every age and stage of life, empowering her patients to freely make reproductive choices whether they involve bearing children or not.

| CEDARS-SINAI.ORG/DISCOVERIES

is also the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science.

18.1% of reproductive-age American women use female sterilization for contraception.

Kotryna Zukauskaite

A one-size-fits-all approach to evaluating blood pressure could be detrimental to women’s health, according to analysis from the Smidt Heart Institute. The higher number of a reading, called systolic pressure, gauges the force of blood against artery walls during heartbeats. The bottom number measures diastolic pressure, or the pressure exerted between heartbeats. For decades, 120 mmHg has been considered the normal upper limit for systolic blood pressure in all adults. But while that number may be safe for men, the threshold of risk for women may actually be 110 mmHg— or even lower—notes Susan

N&N

Potential LiverSaver

Raul Arias

Alcohol-related liver disease is on the rise—especially among younger adults—and the pandemic has only exacerbated the trend. Each year, nearly 100,000 people across the country die from excessive alcohol use, with alcoholic hepatitis a frequent cause. Recently, Cedars-Sinai investigators and their collaborators discovered a potential therapy for the condition that has shown considerable promise in mouse models. The team found that oral administration of a synthetic compound, called 1Z1, stimulates the body to produce a naturally occurring protein, interleukin-22, which shields the liver from injury. “Interleukin-22 can help protect the body against invading pathogens, repair damage caused by intestinal or liver disease, and potentially prevent development of alcohol-associated liver disease,” explains Ekihiro Seki, MD,

PhD, director of Basic Liver Research at Cedars-Sinai and senior author of the study. The mice had no side effects from 1Z1, and that’s an advantage over the current standard treatment—corticosteroids—

12,768 1% average number of birth control pills a woman must take to cover her reproductive years.

of sterilized women obtain a reversal of the procedure.

which reduce inflammation but often cause adverse reactions. Although Seki says further clinical study is needed to confirm the benefits of 1Z1, treatments for alcoholic hepatitis are urgently needed.

46 MILLION

American women ages 15–49 in 2018 were sexually active and not seeking to become pregnant. FALL 2021 | DISCOVERIES |

N&N

Arms Race How Cedars-Sinai teams innovated their way around vaccine hesitancy

immunity in Los Angeles has not been a straight shot, particularly in underserved, minority communities where

| CEDARS-SINAI.ORG/DISCOVERIES

distrust of the medical establishment and limited access have been barriers to vaccination. Cedars-Sinai teamed up with communities to acknowledge concerns, share factual information, and provide access to vaccine super sites, drive-through clinics and neighborhood pop-ups. In partnership with respected healthcare and faith leaders, Cedars-Sinai hosted candid discussions about COVID-19 vaccines via online forums. The dialogues, which reached more than 75,000 people, openly addressed vaccine hesitancy in Black, Latino, Native Hawaiian and Pacific Islander populations. One panelist, Kenneth C. Ulmer, DMin, PhD, bishop and senior pastor of Faithful Central Bible Church in Los Angeles, told the online audience that while straight talk has an impact, serving as a model for getting vaccinated matters more. “Not only did I get vaccinated but I made extra efforts to make sure our congregation knew that I had gotten vaccinated,” he said. Cedars-Sinai’s Community Health Improvement Team helped increase access in other practical ways, too.

They helped vaccinate more than 40,000 Los Angeles Unified School District educators so they could return to in-classroom instruction. Cedars-Sinai also partnered with local organizations, including Boys & Girls Clubs of Metro Los Angeles and Martin Luther King Jr. Community Healthcare, to hold pop-up clinics in neighborhoods with low vaccination rates. “As an African American doctor, I know minority patients want to be taken care of by people who look like them,” said Kyle Monk, MD, a Cedars-Sinai pediatrician who helped staff a South Los Angeles pop-up clinic. “By administering the vaccine and having personally received it, I know I give others confidence to get the vaccine.” Jasmine Onyeka Obioha, MD, a Cedars-Sinai dermatologist who also served as a vaccinator, noted the enthusiasm among those who showed up for shots. “Although there’s a lot of vaccine hesitancy in the minority population, everyone I vaccinated was ready and willing to get the vaccine,” she said. Daria Kirpach

The pathway to a postpandemic world is being paved by COVID-19 vaccines. But achieving herd

N&N Ancestry Matters

Prime Suspect Eva Vazquez

Genetic risk for fatal blood clots identified Blood clots are the leading cause of death in people with inflammatory bowel disease (IBD). A Cedars-Sinai-led study

has discovered genetic 5 markers that identify which IBD patients are at highest risk of developing these potentially

fatal complications. “The genetic signature we found more than doubled the risk of developing potentially fatal blood clots in approximately 1 in 7 IBD patients,” says Dermot P. McGovern, MD, PhD, director of Translational Research in the Inflammatory Bowel and Immunobiology Research Institute, and the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics. Although gastrointestinal inflammation, age, pregnancy and other factors can be a risk factor for blood clots, “very little was known about the impact of genetics,” McGovern notes. To fill that knowledge gap, investigators assessed the genetics of 792 IBD patients and then identified patterns associated with the development of clots in veins and arteries. The ability to identify high-risk patients could lead to treatment improvements. “Understanding the influence of the small and large genetic variants we identified would enable physicians to provide more precise or personalized medical care,” McGovern says.

Genetic risk factors for inflammatory bowel disease (IBD) differ dramatically between African Americans and people of European ancestry, according to a pioneering study co-led by Cedars-Sinai. Investigators analyzed the genes of more than 1,700 patients who have Crohn’s disease or ulcerative colitis, the most common forms of IBD. The results found that the most important genetic risk factor for IBD in African Americans is a relatively minor factor among whites. Conversely, genes associated with IBD in whites play smaller roles in contributing to disease development among those of African descent. The landmark study also found rare genetic variants underlying IBD risk in African Americans that had eluded previous research. “One of our goals in treating IBD is to move toward a more personalized approach,” says Dermot McGovern, MD, PhD, director of Translational Research in the Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai, and the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics. “Deciphering genetic architecture is vital to ensuring that diverse populations benefit from the tremendous advances promised by genomic medicine.”

FALL 2021 | DISCOVERIES |

N & N TECH CORNER

The Alzheimer’s Maze A specially designed maze opens possible avenues toward detecting Alzheimer’s disease Nearly 6 million Americans are living with Alzheimer’s disease—and ultimately dying from it. With a cure remaining elusive, the challenge is to diagnose Alzheimer’s early so its harm can be delayed. However, few ways to detect early Alzheimer’s disease are available and “clinical diagnosis has been largely focused on behavior and cognitive function,” according to neuroscientist Maya Koronyo-Hamaoui, PhD, an associate professor in the Department of Neurosurgery. “Visual dysfunctions in Alzheimer’s are severely understudied.” So she set about inventing a potentially better approach to assess whether vision impairment could be linked to cognitive decline.

THE PATH With her Cedars-Sinai colleagues Yosef Koronyo, MSc, LLB, and Keith L. Black, MD, chair of Neurosurgery, director of the Maxine Dunitz Neurosurgical Institute, and the Ruth and Lawrence Harvey Chair in Neuroscience, KoronyoHamaoui devised a testing maze for mice with Alzheimer’s that could identify visual deficits and lead to better techniques for early diagnosis. Their x-shaped creation, the visual-stimuli four-arm maze (ViS4M), features programmed

lights of various colors and intensities, along with grayscale objects. The device builds on the researchers’ previous discoveries about Alzheimer’s effects on the eye’s retina. “Our studies have shown that retinal abnormalities and visual impairments can appear early in the disease,” Koronyo-Hamaoui says. To examine sight-related changes that occur in mice with Alzheimer’s and compare them with their healthy brethren, the ViS4M’s different color wavelengths each activate a unique population of retinal cells—known as photoreceptor subtypes— that are important for different visual functions and color discrimination. The grayscale shapes are used to assess the mice’s ability to differentiate between an object and its surroundings. Once in the ViS4M, mice could freely explore its corridors, with no treats or inducements to attract them to one route over another. As the mice entered and re-entered the maze, investigators collected data about their subjects’ response to color and contrast stimuli, speed of progress and cognitive function.

THE DISCOVERY In a study published in Nature Scientific Reports, the investigators found that normal mice explored the maze’s

| CEDARS-SINAI.ORG/DISCOVERIES

corridors in specific patterns, suggesting that they remembered the arms previously visited and also detected changes in color and intensity of light. By contrast, the Alzheimer’s-model mice were less able to alternate and transitioned more often between the same two arms. Repetitious movements made by these mice were not random but instead were linked to wavelength- and intensity-specific loss of visual discrimination. This mirrors the defects documented in some Alzheimer’s patients.

THE SIGNIFICANCE Mazes have long been used in Alzheimer’s research. The disease itself seems like an inescapable maze of constantly shifting paths and dead ends that eventually break down the mind and body. The ViS4M represents a step forward by identifying “early and progressive impairments in color vision and contrast sensitivity in the mice with Alzheimer’s,” Koronyo-Hamaoui notes. Going forward, she adds, the ViS4M could enable vision and cognitive-behavioral scientists to make discoveries in rodent studies that could potentially be translated to improved human visual testing and early diagnosis of Alzheimer’s.

Bill Pollard

THE NEED

TECH CORNER

N&N

FALL 2021 | DISCOVERIES |

N&N

Training for Surgery, Like an Athlete ogy. “Surgical training has never been objective like that.” Prior to medical school, Kim, the Board of Governors Chair in Gynecologic Oncology, was a certified pro tennis coach—and leveraged this expertise to help develop the SimNow simulators. “To get my tennis pro certification, I was required to take courses in swing mechanisms and body kinetics,” Kim says. “When I became a surgeon, I applied this to how I teach surgery.” When using robotic-assisted surgery and more complex surgical systems, Kim says surgeons have to overcome two learning curves: how to use the surgical tools with the proper technique

and then how to perform the procedure itself. Kim describes training residents with the SimNow as similar to a “wax on, wax off ” approach, as seen in the movie The Karate Kid, only “the goal is to master surgical techniques that you’re going to apply in actual surgery,” he says. The impact that roboticsurgery simulators have on residents’ surgical abilities is something Kim has seen firsthand. “The improvements are palpable and noticeable,” he says. “At Cedars-Sinai, we have so many excellent robotically trained surgeons, we’re really poised to do it better than anyone else.”

Cancer cells are skilled at evading the body's immune system. This is especially true of prostate cancer, the second most common cancer—and a leading cause of death—in men. Cedars-Sinai investigators have discovered a way to transform tissues surrounding prostate tumors to alert the body’s immune cells to the cancer and help fight it. Using a technique called epigenetic reprogramming, scientists altered tumors and their microenvironments in mouse models. Epigenetics relates to how genes are switched on and off to produce proteins for fulfilling different functions. Disruptions to the process can form cancerous cells. The team focused on inhibiting a protein that shields cancer from attack by immune cells. If confirmed in clinical trials, the findings could lead to improved immunotherapies for prostate cancer. Currently, up to 85% of patients receiving immunotherapy drugs fail to respond to them. “Our goal is to fire up the immune system of prostate cancer patients and make the cancer vulnerable,” says Leigh Ellis, PhD, scientific director of the Center for Urologic Research Excellence. Dan Page

Kenneth Kim, MD, MHPE, didn’t know that his backhand would come in so handy during his surgical training as a resident. Since 2020, surgeons here have been using simulators to teach residents how to perform robotic-assisted procedures and improve surgical performance. Unlike other robotic surgerytraining systems, the SimNow by da Vinci is designed to help train surgeons like athletes. “In professional sports, there are so many technologies to measure performance and figure out optimal body mechanics, like bat speed in baseball,” says Kim, director of Gynecologic Oncol-

Immune Cell Booster

| CEDARS-SINAI.ORG/DISCOVERIES

N&N

Stroke Safety

Adria Fruitos

Stop Signal Neurons Spotted We’ve all done it—taken our foot off the brake while stopped at a traffic light, only to reapply it because the signal is still red. That immediate correction is triggered by the appropriately named “stop signal neurons,” charged by our brain with canceling potentially harmful actions. When this automatic ability fades, it can lead to the unwanted movements associated with Parkinson’s disease and other neurological disorders. Parkinson’s disease, which affects nearly 1 million people in the U.S. alone, leads to a paradoxical mixture of uncontrolled, involuntary movements and

an inability to move. How this process occurs and what regions of the brain are responsible for it have remained elusive despite years of intensive research. Now, Cedars-Sinai investigators have solved part of this longstanding mystery. “This firstin-human study identifies the underlying brain processes required for stopping movements,” notes Ueli Rutishauser, PhD, the Board of Governors Chair in Neurosciences. Investigators studied patients with Parkinson’s disease undergoing deep-brain stimulation, a common surgery for the disease

that implants tiny electrodes in the basal ganglia—the brain region that regulates motor control—to block excessive movement. The researchers discovered that neurons in one part of the basal ganglia region—the subthalamic nucleus—indicated the need to “stop” an already initiated action. These neurons responded very quickly after the appearance of the stop signal. They had never before been observed “in action” in humans. The discovery provides the ability to more accurately target deep-brain stimulation electrodes.

Intracranial artery stenosis—the narrowing of brain arteries from cholesterol buildup—is a major cause of stroke, the fifth-leading cause of death in the U.S. Some 25% of strokes are repeat events, and medications are the most commonly used means to prevent recurrence. But nationwide research headed by Cedars-Sinai previously showed that, just as stents are used to widen cholesterolclogged arteries in the heart, a similar method may be effective in the brain. Results from a Cedars-Sinai-led follow-up study provide additional evidence that a specialized stenting system could be as good or better than traditional therapies for certain patients with a history of stroke. The latest study followed a group of stented patients for one year. The results showed a nearly 4% reduction in strokes and fatalities from a previous study using medical therapy alone, according to Michael Alexander, MD, director of the Cedars-Sinai Neurovascular Center. “Our findings lend support that stenting for intracranial atherosclerotic disease can be performed safely, with apparent clinical benefit at the one-year follow-up,” Alexander says.

FALL 2021 | DISCOVERIES |

N & N COVID-19 RESEARCH

The Flu, Eclipsed Experts wonder when, not if, it will return Last year, the magnitude of the COVID-19 pandemic overshadowed the absence, for the first time in recorded history, of our usual pandemic: the flu. That event—or nonevent—has left epidemiologists with questions about the 2021 flu season.

In Los Angeles and around the world, an extreme drop in cases effectively canceled flu season—from October 2020 to May 2021, Cedars-Sinai didn’t treat a single patient for influenza. “Not even one, and it’s not for lack of testing—it just wasn’t

present,” says Michael Ben-Aderet, MD, director of Hospital Epidemiology. Public health experts agree that the flu was at least partially stifled by widespread masking and physical distancing, school closures and travel slowdowns— measures meant to disrupt the spread of COVID-19. Though no one missed the flu, its disappearance could have

negative consequences for vaccine efficacy this coming season. Scientists tweak the flu vaccine to target the strains they predict will be circulating in any given year. Vaccine development is always an educated guess, based on data from the prior year. But in a year without data, preparing shots for 2021–2022 could be more of a gamble than usual. Either way, what does Ben-Aderet expect this winter? “On one hand, if we interrupted transmis-

sion of the flu, we may have a mild season because there’s not much virus out there,” he says. “On the other hand, where is the reservoir of influenza lurking? After a resurgence in travel after COVID-19 vaccinations, we could get a pretty severe flu season.” And influenza is still nothing to sneeze at. “Every year we track the flu—it’s the No. 1 viral illness,” Ben-Aderet says. “It’s always possible we’ll have another novel outbreak. The flu is out there.”

Each of us has around 500 million sacs in our lungs called alveoli, which are responsible for exchanging carbon dioxide for oxygen. But when acute respiratory distress syndrome (ARDS) strikes, fluid accumulates in the lungs and the alveoli collapse. The result is severe oxygen deprivation, and it usually affects people who are already seriously ill or injured, such as those with COVID-19. Although most COVID-19 patients have mild respiratory illness, some 20% become seriously ill and require hospitalization due to pneumonia that can advance to ARDS and systemic inflammation. ARDS is associated with poorer outcomes, including lasting lung damage and death. A new study led by Cedars-Sinai elucidates the ARDS/COVID-19 connection. Researchers analyzed the

| CEDARS-SINAI.ORG/DISCOVERIES

immune systems of COVID-19 patients—some with moderate disease, some with ARDS and others in recovery from ARDS—and compared them to people without COVID-19. The team examined the gene transcription process—the first step in the production of proteins that dictate cellular function—in blood cells that are important for immunity and vaccine responses. The results revealed a range of distinctive defects in the transcription processes in ARDS patients. The study supports the concept that COVID-19, especially in patients who have progressed to ARDS, is characterized by impairment of the body's regulation of immune responses. The findings suggest the need for targeted approaches rather than broad application of immunosuppressive therapy.

Juan Bernabeu

At Odds With ARDS

COVID-19 RESEARCH

Look Back for New Answers

Carole Henaff

A century-old vaccine may augment the arsenal against COVID-19

As scientists around the globe rushed to create vaccines for COVID-19, Cedars-Sinai investigators also looked back in time for ways to shield people from the disease. They found one potential avenue in bacille Calmette-Guerin (BCG), a vaccine developed a century ago to battle tuberculosis.

More than 100 million children worldwide receive the BCG shot each year, and the vaccine also has longstanding approval from the Food and Drug Administration as a treatment for bladder cancer. Several studies are currently investigating if BCG vaccination can provide protection against severe SARS-CoV2 infection.

To gauge its potential for stopping COVID-19 infection, researchers tested the blood of more than 6,000 healthcare workers in the Cedars-Sinai Health System. Participants were also asked about their medical and vaccination histories. The study found that those with a history of BCG vaccination—about 30% of the total— were significantly less likely to have tested positive for COVID-19 antibodies than those who had never received the BCG vaccine. They were also less likely to report related symptoms. Similar effects were not shown in those who had only been immunized against the flu, meningitis or pneumonia. “It appears that BCGvaccinated individuals either may have been less sick or they may have mounted a more efficient cellular immune response against the virus,” says Moshe Arditi, MD, executive vice chair for Research in the Department of Pediatrics, director of the Division of Pediatric Infectious Diseases, and the GUESS?/Fashion Industries Guild Chair in Community Child Health. While noting that BCG would not be more effective than the vaccines developed specifically for COVID-19, he calls it “a potentially important bridge that could offer some benefit” in certain countries before the approved COVID-19 vaccines are available for all. “It would be wonderful if one of the oldest vaccines that we have could help defeat the world’s newest pandemic,” Arditi says.

N&N

Respiratory Revelations During the pandemic, unprecedented numbers of people have required serious interventions to assist with their breathing. “We never had this many people receiving this much oxygen,” says Oren Friedman, MD, director of the ICU at Cedars-Sinai Marina del Rey Hospital. “What we’ve learned has a chance of tipping the way we think about respiratory failure.” Friedman cares for the sickest COVID-19 patients, including those on extracorporeal membrane oxygenation (ECMO). An ECMO machine routes a patient’s blood to an oxygenator that adds oxygen and removes carbon dioxide. The blood is then returned to the body. Patients are often given supplementary oxygen or put on a ventilator before being placed on ECMO. COVID-19 patients have frequently needed ECMO for weeks or months. Data collected by Friedman and his colleagues found that maintaining patients on breathing machines and supplemental oxygen for long periods can cause additional lung damage. This finding confirms the longstanding belief that patients could benefit greatly if they are switched to ECMO earlier in their course of treatment.

FALL 2021 | DISCOVERIES |

N & N WHO’S WHO

Nourishing Faith and Racial Equity NAME:

Calvin Johnson, MD Anesthesiologist [Faithful deacon, inclusion advocate and family man] Chickens, vegetable gardens, a pig, a cow— Calvin Johnson’s family might not have had much materially, but he never went hungry: His diet was sourced straight from the land. One of eight children, the Cedars-Sinai anesthesiologist grew up on an 11-acre family farm in Western Michigan. It was a place that nourished him, where he could run fast and far, and where he developed into a talented athlete. It’s also the first place where he saw the ugliness of racial prejudice. As a Black man practicing medicine, Johnson now pushes back against stereotypes and inequality and is committed to rooting them out. “Having difficult conversations and sharing our experiences—that’s the best approach,” he says.

FACING THE “MOB MENTALITY” A basketball point guard, Johnson’s first exposure to racism was as a high school sophomore. The team had driven a few hours away to a rural white community, and he was the only Black

diverse medical student force to Cedars-Sinai.

HONORING FAITH AND FAMILY Johnson’s Christian faith has come first, with family a close second. He merges the two serving alongside his wife, Elaine, at South Bay Church of Christ, where they are deacons. They draw on their 36-year marriage and

journey as the parents of three adult children to counsel other families. Faith has given him conviction, strength and gratitude—even during the pandemic and social unrest—which “made the world slow down and evaluate humanity and life.” “I’m very, very hopeful,” he says. “I know that God’s in control.”

student on the court. “Just as I was preparing to shoot, another student screamed out a racial slur,” he recalls. “There were about 500 people in the stands. No one said a word. This is where the mob mentality kicks in.” Soon, 10 to 15 other students joined in the shouting. The best treatment for a mob mentality like that? Addressing biases in a constructive way, Johnson suggests. “Cedars-Sinai is being proactive,” he says, referring to a host of diversity and inclusion efforts, especially those fostering dialogue.

BLACK MEN IN WHITE COATS One huge crisis is the lack of Black representation in medicine, says Johnson, who recently hosted a Cedars-Sinai screening of Black Men in White Coats, a documentary on the issue. A long history of healthcare injustices has kept many Black patients away from medical care, but having more doctors who look like their patients can help foster trust and repair disparities, he says. Johnson still remembers the time an elderly

| CEDARS-SINAI.ORG/DISCOVERIES

Bill Pollard

RURAL ROOTS

patient told him he had made her day—because she had never even seen a Black doctor, let alone been treated by one. “She felt safe with me,” he says. Representation is even more vital now because of COVID-19, which has overwhelmed communities of color, he adds. Johnson is working with mentorship programs to recruit an even more

N&N Women's Hearts at Risk

Colorectal Care

Nicole Xu

Aspirin linked to lower risk of cancer metastasis and death Long-term, regular use of aspirin—at least 15 times per month—prior to diagnosis may enhance the odds of beating colorectal cancer. New research by Cedars-Sinai investigators shows that aspirin may lower the rate of metastasis, or tumor spread. In contrast, non-aspirin alternatives such as ibuprofen, acetaminophen and naproxen failed to reduce such spread. Nor did starting aspirin after diagnosis achieve the same benefits. “More evidence is needed, but this association between aspirin and lower death rates is highly significant,” says Jane C. Figueiredo, PhD, MSc, an

epidemiologist and director of Community and Population Health Research at the Samuel Oschin Comprehensive Cancer Institute. “These findings may provide an inexpensive lifestyle option to people seeking to prevent colorectal cancer.” While ongoing clinical studies will provide additional guidance, Figueiredo encourages patients and clinicians to discuss risks and benefits, as daily aspirin use may increase the risk of allergic reactions and internal bleeding. Colorectal tumors are the third-leading cause of cancer deaths among adults in the U.S.

Recent research from the Smidt Heart Institute shows that between 10 p.m. and 6 a.m., women are more likely than men to die from sudden cardiac arrest. The question remains why. These findings are especially mystifying since the sleep resting state reduces metabolism, heart rate and blood pressure. The study examined 3,208 daytime cases of sudden cardiac arrest and 918 nighttime cases. Compared with daytime cases, patients who suffered from nighttime cardiac arrest were more likely to be female. In some conditions, though, the hazards were shown to be more evenly distributed. The prevalence of chronic obstructive lung disease and asthma were found to be significantly higher in sudden cardiac arrest cases at night compared with daytime cases, regardless of gender. Individuals taking medications that could affect brain function, such as sedatives and drugs prescribed for pain and depression management, were also at higher risk. Based on these findings, it is recommended that physicians exercise caution when prescribing brainaffecting medications to high-risk patients— especially women.

FALL 2021 | DISCOVERIES |

Meet

Q A &

Life to the Fullest: Transplant Surgery Trailblazer Irene Kim, MD By Victoria Pelham

Quick on her feet, Irene Kim, MD, does not let a single moment slip away from her. The co-director of Cedars-Sinai’s Comprehensive Transplant Center, mom of two and avid runner has learned to expect the unexpected—and pivot accordingly. Set to take the reins as center director this December, she opens up about what drives her, the gift of life and what’s ahead for organ transplantation.

Q. What drew you to transplant surgery?

Q. What are you most proud of?

During my residency at Tufts Medical Center, three transplant surgeons, to me, embodied humanism, compassion and surgical prowess. They inspired me, and I decided I wanted to pursue this career. People really tried to dissuade me. They said it was a difficult field with no protected hours and that I would have no life. But I just couldn’t break from this notion of what being a surgeon meant to me and how you are able to actually save someone’s life through organ transplant. There’s something about that feeling of one family making this huge sacrifice to save another person that is so special. The field I chose is hard, but I have no regrets. I absolutely love what I do. I love my patients.

I am most proud of the contribution I’ve made to creating a cohesive transplant team that really cares for our patients and for one another. I’m proud of my leadership in helping to create that team, whether it’s the physicians I’ve personally recruited or the example I hope I provide. I’m also proud of the research I’ve done that can be applied directly to care, especially my investigation into the effects of blocking inflammatory molecules that trigger an immune response. This allowed us to suppress the production of antibodies that would attack the new organ. It enables transplantation in people with strong antibody responses and increases graft lifespan after transplantation.

| CEDARS-SINAI.ORG/DISCOVERIES

Q. How do you find balance across all the different aspects of your life?

My parents retired when our daughter turned 1. They moved into our house in Los Angeles and they help us out a lot with our family. It is a rare situation. It’s partly cultural but also just the goodness of my parents’ hearts. There’s a definite surprise element in transplantation, because it’s based on generosity and the incredible gift of donors. Transplants often happen at nighttime, on the weekends and at random hours of the day. And they’re long operations; a liver transplant can take six, eight, sometimes 12 hours. My family, in turn, has to be flexible. They know that when I’m on call they’re on call, and they fill in the void when I’m not there. My kids are very resilient—they

understand that and know when Mommy has to be away. Q. As you take the helm, what is your vision for the future of the Comprehensive Transplant Center?

We are going to continue to expand as a transplant program. We are already leaders in many aspects of transplantation. I want to see Cedars-Sinai get out ahead in relatively young transplant fields such as hand and limb transplants. And as we develop more research around barriers in transplantation, I hope we will be able to overcome them—for example, for patients who have immunologic obstacles preventing them from being transplant candidates. I also want to focus on equity and inclusion. Many marginalized communities are not given access to transplantation, whether it be due to language or socioeconomic or immigration status. I see us participating in outreach efforts for patients who might need a liver or kidney transplant but have not been introduced to that as a concept.

IRENE KIM, MD Co-Director, Comprehensive Transplant Center Surgical Director, Kidney Transplantation FAMILY AFFAIR Kim met her husband in medical training. After a decade of marriage and a cross-country move, their daughter, 6, and son, 3, were born at Cedars-Sinai. The couple both have demanding careers, one in medicine and the other in a technology strategy firm, but they always try to eat dinner together as a family. “My Korean heritage is important to me, so our family meals are usually influenced by Korean culture,” Kim says. SETTING AN EXAMPLE Surgical fields have lagged behind in diversity, Kim says. She was the first woman to join Cedars-Sinai’s transplant surgery group. “I hope that I serve as an example that you can be a woman and a person of color and be a very welcome, necessary part of a surgical team.” RACING AHEAD With an erratic surgery schedule, she squeezes in a run whenever she has a spare hour and a half. Whether with friends or on her own on trails, running is her main release. Dr. Irene Kim wants to remove barriers to organ transplantation.

Bill Pollard

Q. Where do you think transplant medicine is headed?

There hasn’t been a newergeneration medication to prevent organ rejection in over 20 years. The goal is minimizing the quantity of medications

that a transplant patient has to take, then cutting down on adverse side effects. The holy grail is reaching a state where patients may not need immunotherapy at all. The other main challenge is the lack of organs. Many

patients die waiting for an organ transplant. An old mentor used to tell me, “If they grew on trees, we’d be transplanting left and right.” So why can’t we get them to grow on trees? Why can’t we create a bioartificial organ? FALL 2021 | DISCOVERIES |

Learn

Trading Places By NICOLE LEVINE The challenges of the COVID-19 pandemic have demanded that healthcare providers flex all their clinical muscles. For some, that means changing jobs—trading suits for scrubs, Oxfords for Crocs or scalpels for syringes. Others have stepped out of exam rooms and into parking structures. This agility keeps the health system operating smoothly. Here, care providers share how their daily duties have changed to make the best use of all their skills—and to meet the needs of patients and the community during the pandemic. CHELSEA HAHN, RN: FROM THE SPINE CENTER TO THE BEVERLY CENTER USUAL JOB: Nurse in the Spine Center

helping patients with back and neck problems PANDEMIC JOBS: Hahn volunteered in Urgent Care and then at a drive-through COVID-19 testing site that served as many as 600 patients a day. Most recently, she was clinical leader for the COVID-19 vaccination clinic at the Beverly Center. SAFETY FIRST: “At the testing site, we focused on keeping our patients safe and explaining to them why we were doing such an invasive test. Lots of people were scared. But it was gratifying to see people and have that instant of making them feel better in a difficult moment.” LIGHT AT THE END OF A LONG TUNNEL:

“I’ll always remember our first cohort of vaccine recipients. They were the 65-andolder crowd. They hadn’t been out of their houses for a whole year. They were so happy to see another human being. Behind their masks, you couldn’t see the smiles, but you could see them glowing. It was the beginning of them getting to see

| CEDARS-SINAI.ORG/DISCOVERIES

their grandchildren again, hugging their sons and daughters again.” RANDY SHERMAN, MD: BEST SHOT USUAL JOB: As director of Plastic Surgery

and the General William and Willa Dean Lyon Family Chair in Reconstructive and Plastic Surgery, Sherman leads a team of surgeons that rebuilds limbs and organs lost to disease or injury, reconstructs nerves, manages complex wounds and more. PANDEMIC JOB: Sherman pivoted to administering COVID-19 vaccines. ANSWERING THE CALL: “The reason why is about as simple as it can be: It just seemed like the right thing to do! Surgeons were really forced to abdicate most of their cases to make way for the care of COVID-19 patients. Nurses were giving vaccines and it was straining the system because those nurses were badly needed in other places. So when the call came out asking for volunteers, it was really, really easy to go fulfill that role.” PITCHING IN: “When there’s a fire, you either run away from it or you throw water on it. You might not be the head of the fire brigade, but you can contribute.”

ALAINA ARMENDARIZ, RN: LABORS OF LOVE USUAL JOB: She’d just transferred to her

dream nursing job in Labor and Delivery. “My colleagues didn’t even know what I looked like without a mask yet.” PANDEMIC JOB: She returned to a postsurgical unit. FORGING RELATIONSHIPS: “As nurses, you get attached to your patients. In Labor and Delivery, they come and go quickly, and mostly they’re healthy. My postsurgical patients were often with us for extended periods of time, sometimes for a month or more. I was their nurse, and I was doing caregiver and family roles, answering phone calls, updating their loved ones. In some ways, I grew more attached to my patients than I ever had before.” KEEPING PERSPECTIVE: “We go where we’re needed and do what we need to do. In World War I and II, nurses were asked to go above and beyond and sacrifice. It’s some of the same things for different reasons. We always find a way to adapt.” GENA SMITH-WOODS, RN: WEARING MORE THAN ONE COAT USUAL JOB: Patient relations team

members like Smith-Woods combine the clinical know-how of a seasoned bedside nurse, the uncanny navigational ability of a longtime administrator and the polish of a

“When there’s a fire, you either run away from it or throw water on it. You might not be the head of the fire brigade, but you can contribute.” Randy Sherman, MD

John Kuczala

Nurse Gena SmithWoods stepped out of her usual role to administer COVID-19 vaccinations in a parking structure at the Beverly Center.

public relations maven. Smith-Woods worked exclusively in the Samuel Oschin Cancer Center helping patients navigate appointments and treatment sessions. PANDEMIC JOB: She and her colleagues were dispatched to areas that most needed their skills on any given day. Among her duties: administering COVID-19 vaccinations at the Beverly Center, making discharge follow-up calls to allow bedside nurses to concentrate on inpatient care, and serving as a liaison for patients and their loved ones. SAME BUT DIFFERENT: “We kept the same mission but adapted to the situation. There was no typical day. A lot of the time, it was about managing the fear and

helping bridge the gaps between patients and their families who couldn’t visit. We got through it with resiliency, empathy and kindness.” CLAIRE ENRIQUEZ, MD: RESIDENT EXPERT USUAL JOB: Enriquez was in a rotation in

Infectious Diseases as a second-year resident when the pandemic hit. PANDEMIC JOB: She continued her residency, but being a resident during a pandemic is a dramatically different experience from the intense but predictable schedule of a newly minted doctor. She worked frequently in the ICU with some of the sickest COVID-19 patients.

LEARNING TO COPE: “I took up bike

riding, and now I try to ride every day. Spending time outside helps me disconnect from the hospital and connect with nature. That little time to focus on me gives me the patience to give 100% when I’m back in the hospital with the people who really need us to take care of them.” GIFT OF PERSEVERANCE: “My mentality and how I approach work day to day changed. If I ever start to feel stressed or a little overwhelmed, I know we will get through it. No matter what happens, I have the resources, people and strength to know we can push through together.”

FALL 2021 | DISCOVERIES |

Think

Three Big Questions About ‘Long COVID’

see if we can identify a common pathway. That knowledge could lead us to an opportunity to treat multiple people—if we can get there. Right now, if we find inflammation in the lungs, we treat it with anti-inflammatory medications— but is that good or bad in the long term, and is it right for everyone? We need to understand what the proper therapies are in the grander scheme of things.

Investigators at Cedars-Sinai are studying critical, pressing questions about long COVID to uncover ways to intervene or treat symptoms. By CASSIE TOMLIN COVID-19 is distressingly unpredictable. About 10% of people recover from an initial illness only to confront a new set of chronic symptoms like fatigue, shortness of breath, “brain fog,” anxiety and depression, kidney damage, gastrointestinal issues, or changes to skin, hair and sense of smell. This range of symptoms, known as “long COVID,” can impact essentially every organ system, persist for months and range from mild to incapacitating. Investigators at Cedars-Sinai are studying long COVID to uncover ways to treat symptoms. Patients are managed by a multidisciplinary team at the COVID-19 Recovery Program, including Isabel Pedraza, MD. We asked Pedraza, as well as COVID-19 researchers Peter Chen, MD, and Susan Cheng, MD, MPH, MMSc, to outline the mysteries they seek to solve.

Why do patients experience long COVID differently? I don’t think one disease process fits all—multiple mechanisms probably drive different types of long COVID. If we can understand what underlies long COVID, we can treat it. We need to look deeply into patients’ experiences, measuring biomarkers, genetics, diet,

| CEDARS-SINAI.ORG/DISCOVERIES

–Peter Chen, MD, assistant director of the Women’s Guild Lung Institute, director of the Division of Pulmonary and Critical Care Medicine, and the Medallion Chair in Molecular Medicine

microbiome, demographics and health disparities to discover which ones play a role in developing long COVID. We want the entire research community to collaborate, like an extension of what we started when we were introduced to COVID-19. I think there are still traits we’ve yet to discover and clinical manifestations we didn’t realize were long-term complications of this disease. We’re enrolling patients with long COVID in a study to

Can long-term impairments from COVID-19 be treated or prevented? At the COVID-19 Recovery Program, led by Catherine Le, MD, almost all patients I see present with fatigue and weakness. How much of that functionality will they gain back? These are things we’re starting

UNRAVELING LONG COVID Long COVID raises a lot of questions, but Cedars-Sinai investigators are seeking to demystify its destructive effects. Studies currently underway include:

•

A long-term study of recovering COVID-19 patients focused on how their immune and inflammatory biomarkers change in relation to their cognitive, physical and social functions (Le)

•

An investigation into why some early COVID-19 patients required ICU care, and whether these patients suffer from long COVID at higher rates (Pedraza and Chen)

•

A study into the role of SARS CoV2 virus “superantigens” that may cause autoimmunity in patients with MIS-C post-COVID syndrome in children (Moshe Arditi, MD,

executive vice chair for Research in the Department of Pediatrics, director of the Division of Pediatric Infectious Diseases and the GUESS?/Fashion Industries Guild Chair in Community Child Health)

to address at the clinic: When and how can we intervene to prevent long-term disability? We know that two-thirds of patients who have pulmonary symptoms and abnormalities get better by three months, so we’re currently operating on a three-month cutoff for allowing people to improve on their own. Maybe intervening early on might help them get there faster; it’s not clear. I don’t want to miss the opportunity to treat them to prevent long-term disability. I’ve only run across a handful of people with long COVID who don’t have anxiety—almost everyone does—and we can’t underestimate the importance of treating people for that. Having COVID-19 is associated with a lot of anxiety because of how the disease saturates the news—but in long COVID, it could be a direct effect of damage to the brain. There is a misconception that, among these patients, it may be a little bit in their head. Of the patients I see, everyone really wants to get back to their normal life. These include active, busy people who want to resume their activities and can’t. What’s most important is to take them seriously and really listen to their concerns. –Isabel Pedraza, MD, director of the Medical Intensive Care Unit

Pep Montserrat

Is long COVID driven by inflammation or autoimmunity? What is causing long COVID—chronic inflammation, reservoirs of the virus living in the body—is hard to determine. In some people with preexisting conditions, maybe inflammation from COVID-19 triggered and lifted the roof on the issues they already had—or made them worse. Is this mostly a reawakening of preexisting conditions—or something

completely new and different? It wouldn’t surprise me if a patient with heart inflammation from their initial COVID-19 infection is at higher risk for long-term cardiac issues, or if really bad lung function during COVID-19 makes someone more likely to have long-term lung issues. But it doesn’t have to be as direct: Low-lying inflammation during the acute illness could lead to chronic inflammation affecting any organ. To home in on what is going on with the immune system, our teams are now focused on asymptomatic patients or those with mild infections who then later on paradoxically suffer these longer-term effects. One theory is that their immune systems were revved up in such a way to

fight COVID-19 that they not only remained overactivated but may even have turned on themselves. A lot of the emerging data are pointing to how, in some people, COVID-19 infection triggers autoimmunity. We’re at the tip of the iceberg. Of patients who have antibodies that attack their own tissues, what makes these people different from those who recover quickly? We need to better understand why they are suffering from these chronic, amorphous, very difficultto-pin-down conditions. –Susan Cheng, MD, MPH, MMSc, director of Public Health Research at the Smidt Heart Institute and the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science FALL 2021 | DISCOVERIES |

HOW TO THINK LIKE A

Sc SCIENTIST

A CRASH COURSE IN SIX LESSONS

What are the practices and mindsets that help drive great science? We asked Cedars-Sinai researchers and experts to weigh in about the processes scientists use to shape their work and drive progress. The pandemic has put science—and scientists—into a white-hot spotlight. For those of us who haven’t spent our lives in the field, the process of science can look confusing. For some, that can lead to an outsized faith in the discipline (“Science is magic!”), while for others, it can give rise to deep skepticism (“Science is bunk!”). The reality is that neither is true. The careful, methodical processes that are the foundation of science have been honed over centuries, and scientists follow them for good reason. But science also has flaws, just like any human endeavor. Still, its larger aim of understanding the world more clearly through observation

and experiments is one that most of us can get behind. So what does the work of a scientist really entail? How do researchers think about scientific questions and try to solve them? How do they make sure their output is good and that their very best ideas make it out into the world to improve lives? Sure, you could carve out the next decade of your life to earn an MD or PhD and find out for yourself. Don’t have that kind of time? We’ve condensed some of the most important insights about scientific thinking into a six-lesson minicourse you can take right now. Let’s get started.

By ERIN PETERSON Illustration by BRIAN STAUFFER

| DISCOVERIESMAGAZINE.ORG

HOW TO TH I NK LI KE A SC I ENTI ST

TRIAL AND ERROR

LESSON

Refine your questions

By the time we’re old enough to speak in sentences, we’re asking questions: Why is the world this way? How can we make it better? Scientists ask versions of these questions, too—and the stakes of the questions they choose to ask can be as high as life or death. “You’ve got to ask questions you’re genuinely excited to know the answer to, because there’s a good chance you’ll spend months—if not years—addressing them,” says Joanna Chikwe, MD, founding chair of the Department of Cardiac Surgery.

THE BIG ASK: CREATING A BETTER RESEARCH QUESTION We asked a few scientists to share the rules they follow when generating their research questions. Here’s what they told us.

A Pursue the surprising observation. “A good question is one in which someone looks at a problem and they notice something—they see something that is different from what other people see. And then the question is: why?” –Keith Black, MD, chair of the Department of Neurosurgery, who studies the biology of the blood-brain barrier

Pose a question in which any answer will illuminate something that matters. “One of my mentors taught me that a worthwhile research question—one that’s worth your time, effort and resources—is one in which the answer, whether positive or negative, will be interesting either way. If you know that an intervention doesn’t work, for example, is that still important?” –Susan Cheng, MD, MPH, MMSc, director of Public Health Research in the Smidt Heart Institute, who asks questions about cardiovascular aging

Think ahead to your next questions. “It’s a little like chess, where you’re thinking four moves ahead. Sometimes that means you have to rethink the chess game if the answers are leading in another direction—but you’re always thinking ahead. There’s never a ‘final question’ until we get to the meaning of life.” –Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, who investigates neurodegenerative diseases

| DISCOVERIESMAGAZINE.ORG

Benedetto Cristofani

HOW TO TH I NK LI KE A SC I ENTI ST

CASE STUDY

Joey Guidone

THE QUESTION THAT SAVED A DECADE’S WORTH OF WORK Joanna Chikwe, MD, was stuck. She knew that patients with a heart condition known as a leaky mitral valve could choose one of two major types of valve replacements as part of their treatment: a valve made of animal tissue or metal. Either way had trade-offs. An animal-tissue valve would need to be replaced after a decade or so, requiring surgery. A metal valve would last longer but would require patients to take a daily blood thinner and lead to a slightly higher risk of stroke. But doctors didn’t know whether one choice might ultimately give patients a longer lifespan. The gold-standard study for such a question was a large, randomized trial, requiring researchers to follow two groups of patients for a decade or more. It would be expensive and time-consuming, and doctors wouldn’t have good answers for their patients for years. “It wasn’t practical,” Chikwe says. She ruminated on the problem until one day she had what she describes as “a classic lightbulb moment.” What if instead of collecting data for many years into the future, she and colleagues sifted through data from patients who had undergone similar procedures during the past 15 years and measured those outcomes? It was a way of using the past to help peer into current patients’ futures. Chikwe and her colleagues tracked down data from thousands of patients who had surgery for the condition during the previous 15 years. With support from a biostatistical team, they controlled for many variables that could have influenced the outcomes. It wasn’t a perfect recreation of a clinical trial, but Chikwe got access to valuable information far more quickly than she could have with a study started in the present. The results? Survival rates were essentially identical, no matter which valve was chosen. For Chikwe, an insightful reframing made all the difference. “When you’ve got a really important question with a number of ways to answer it, your goal is to recognize its limitations while maximizing its strengths,” she says. “If you do it well, you can make a profound difference—you can help patients make an informed decision on something that can alter the course of their life.”

LESSON

Collaborate strategically to amplify great ideas

We’re all familiar with the lone genius myth—a wild-haired scientist mixing burbling chemicals in a basement laboratory— but the reality is that the best scientists team up with others to pursue ambitious work. Here’s how they find the right collaborators to solve big problems. FORMULA

THE POWER OF MORE Paul Noble, MD, director of the Women’s Guild Lung Institute, has spent his career studying the mechanisms of lung inflammation and fibrosis. He’s made many of his career decisions with collaboration explicitly in mind: His roles at Johns Hopkins University, Yale University, Duke University—and now, Cedars-Sinai—have been driven by his desire to propel great research with the very best partners. “Collaboration has been one of the most salient aspects of my scientific career development,” he says. What’s the formula for success? On the next page, he spells it out.

FALL 2021 | DISCOVERIES |

HOW TO TH I NK LI KE A SC I ENTI ST

LESSON 2

F E AT U R E D E X P E R T S

(GOOD IDEA + ADVANCED TECHNOLOGY) x RESOURCES = DISCOVERY

SCIENTIFIC SKILLS + BIG VISION = LEAPS FORWARD

During an early-career fellowship at the University of Colorado and the National Jewish Health research center in the early 1990s, Noble was investigating immune cells known as macrophages, which seemed to be malfunctioning in ways that led to lung scarring. He identified a specific sugar, a glycosaminoglycan, that was modified in lung inflammation and triggered macrophages to drive the scarring. He wrote a paper on the finding. Eager to learn how this sugar could induce genes that might be influencing these activities, he found a team at Johns Hopkins that had developed new technology to identify genes that were expressed by cells grown in culture. It was just what he needed. With support from the National Institutes of Health (NIH), Noble joined the Johns Hopkins team to learn these techniques and technology. Ultimately, he identified a handful of genes linked to this type of lung scarring.

Later in Noble’s career, when he was at Duke, he pondered a fundamental question: Where do the cells that cause scarring come from? There was a raging debate about whether they might come from the lining of the lungs, called the epithelium. To test the idea, he’d need some help. He zeroed in on Brigid Hogan, PhD, a brilliant developmental cell biologist also at Duke who had been a pioneer in developing the technique called “lineage labeling.” The process could help Noble follow the fate of these epithelial cells. Noble was ready to support the collaboration with funding, and a bright, budding pulmonary physicianscientist in the Duke fellowship led the charge in Hogan’s lab. In the end, Hogan was moved by Noble’s pitch that their work could fuel progress in the field and ultimately improve lives. “It’s about persuading others,” he explains. “Can I get them excited about the larger vision?”

TIME x SUCCESS = CREATE YOUR SCIENTIFIC DREAM TEAM For many scientists, including Noble, achieving their biggest scientific goals requires them to move to where the best collaborators are at the time.

The payoff of this approach often comes much later. Since joining Cedars-Sinai in 2013, Noble has assembled a group of talented physicians and

scientists who can propel big projects. “Because of the resources we have here, I’ve been able to bring together people I’ve always wanted to work

with,” he says. “Collectively, we work to find new treatments for advanced lung diseases.”

KEY INSIGHT

THE FINE LINE BETWEEN COMPETITION AND COLLABORATION Shelly Lu, MD, director of the Karsh Division of Gastroenterology and Hepatology, and José M. Mato, PhD, a research professor at the CIC bioGUNE in Bilbao, Spain, have collaborated for decades. They’ve coauthored more than 100 papers on such topics as liver injury. Lu explains their success. “It’s important to work with people who you trust and have expertise that complements yours, because you won’t succeed if you don’t have more than one point of view,” she says. “As a Spaniard, Mato is mainly funded by Spanish and European grants. We’re not competing for resources, we’re pooling them.”

| DISCOVERIESMAGAZINE.ORG

Keith Black, MD Chair, Department of Neurosurgery Director, Maxine Dunitz Neurosurgical Institute Ruth and Lawrence Harvey Chair in Neuroscience Susan Cheng, MD, MPH, MMSc Director, Cardiovascular Population Sciences, Smidt Heart Institute Director, Public Health Research, Smidt Heart Institute Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science Joanna Chikwe, MD Chair, Department of Cardiac Surgery Irina and George Schaeffer Distinguished Chair in Cardiac Surgery in honor of Alfredo Trento, MD Robert Haile, DrPH, MPH Director, Cancer Research Center for Health Equity Associate Director, Population Health Sciences, Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Chair in Cancer Population Health Sciences Shelly Lu, MD Vice Chair, Basic Science and Translational Research Director, Karsh Division of Gastroenterology and Hepatology Women’s Guild Chair in Gastroenterology Gideon Manning, PhD Historian of Medicine, Cedars-Sinai Eduardo Marbán, MD, PhD Executive Director, Smidt Heart Institute Mark Siegel Family Foundation Distinguished Chair Paul Noble, MD Chair, Department of Medicine Director, Women’s Guild Lung Institute Vera and Paul Guerin Family Distinguished Chair in Pulmonary Medicine Zul Surani, MPH Director, Community Outreach and Engagement, and Operations, Cedars-Sinai Cancer Research Center for Health Equity Clive Svendsen, PhD Executive Director, Cedars-Sinai Board of Governors Regenerative Medicine Institute Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine David Underhill, PhD Chair, Department of Biomedical Sciences Janis and William Wetsman Family Chair in Inflammatory Bowel Disease Jennifer Van Eyk, PhD Director, Advanced Clinical Biosystems Research Institute Director, Basic Science Research, Barbra Streisand Women’s Heart Center Erika J. Glazer Chair in Women’s Heart Health

HOW TO TH I NK LI KE A SC I ENTI ST

RULES OF THUMB

WAIT, WHAT DOES BIAS LOOK LIKE? Bias is often so subtle that it’s easy to miss on a project-by-project basis. Here are just two ways that it can prevent or impede good science.

COMMON BIAS #1:

THE BIAS OF RESEARCH DIRECTION

3 LESSON

Benedetto Cristofani

Understand common biases and work to prevent them

Bias can be as simple as hoping for a certain outcome in an experiment—but its tentacles can be far-reaching and harmful. Good science requires investigators to systematically identify certain types of bias and take steps to avoid them.

When the interests of researchers and the funding of science and medicine as a whole don’t reflect the needs of the larger population, important problems can get overlooked, says Gideon Manning, PhD, a historian of medicine at Cedars-Sinai. For example, one study found that both federal funding and philanthropic support are significantly higher on a per-affected-individual basis for cystic fibrosis—a condition that affects primarily white people—than for sickle cell disease, a condition with many similar impacts that is more likely to affect Black patients. Another study found that cancers linked to stigmatized behaviors—like lung cancer—get relatively less philanthropic support than other types of cancers. Some types of menopause research and funding lag significantly behind that for women’s reproductive health. “Values enter into the choices about what gets investigated and what gets funded,” Manning says. “For that reason, we want to get many diverse voices involved in the decision-making process.”

COMMON BIAS #2:

THE BIAS OF HOPE Many scientists are motivated by the desire to improve the world, and science offers a tantalizing opportunity to solve hard problems. But getting too invested in a specific outcome has its own problems. Careers and companies can get built on faulty research premises. “If you’ve spent years discovering a particular signaling pathway that you think is the cause of cancer, you don’t want it not to be the cause of cancer,” says Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. “But you can’t be attached to the outcome of a research question: It’s emotionally wrong. It’s against scientific principles.” That’s why he reminds trainees to stay invested in the process of science, regardless of any specific outcome. “If you’re asking questions and you’re getting answers, no matter what the answers are, you’re winning,” he says.

FALL 2021 | DISCOVERIES |

HOW TO TH I NK LI KE A SC I ENTI ST

LESSON 3

THE COVID-19 PIVOT

IS THIS WHAT SCIENCE WITHOUT BIAS COULD LOOK LIKE?

KEY INSIGHT

BUILD AN INCLUSIVE GROUP TO FUEL SMARTER RESEARCH QUESTIONS Zul Surani, MPH, of the Cedars-Sinai Cancer Research Center for Health Equity knows that bias can take unexpected forms. When he and his team developed a survey of community health in L.A., they were eager to expand its reach by translating it into Korean and giving people the option to fill it out on their smartphones. But “with so many more characters in Korean than in English, it just didn’t work,” he says. As he and his team worked relentlessly to make the survey more user-friendly, early pilot tests alerted them to the problem—and gave them time to correct it. Overcoming obstacles like these is just one of the many reasons that Surani and Robert Haile, DrPH, MPH, the center’s director, have aimed to integrate outreach and commu-

nity advisory boards into every step of their research process. The team has an LGBTQ+ advisory board, a Korean community network, a Filipino network and a Latino community advisory board, among others. These groups play an essential role in helping researchers understand nuances that can have a big impact, like cancer-screening guidelines that don’t feel inclusive to trans or nonbinary individuals, and may be linked to lower screening rates. Advisory boards also help researchers test assumptions, hone questions, and develop research and interventions that actually work. “Without this type of inclusivity, disparities may be invisible,” Surani says. “We’re constantly trying to create that visibility, because it makes a big difference.”

| DISCOVERIESMAGAZINE.ORG

4 LESSON

Embrace the rigor of publication

The unique and challenging process of scientific publication can help root out the most egregious mistakes in research before they reach a wide audience. The process isn’t perfect, but it’s been honed over the course of centuries— and continues being tweaked to help illuminate the best work. HISTORY LESSON

A TIME-TESTED APPROACH The peer-review process in science requires authors of scientific papers to have their work assessed by other experts in the field to determine its worthiness for publication in a journal. The first fully peer-reviewed journal, Medical Essays and Observations, was published by the Royal Society of Edinburgh in 1731.

Joey Guidone

If we’ve learned one thing during the COVID-19 pandemic, it’s that big goals, big budgets and laser focus can lead to incredible progress. Many assumed that it would take a decade or more to produce an effective COVID-19 vaccine, but multiple highly effective vaccines were produced within a year. Such work happened, in part, because so many different ideas and groups brought their perspective and insight to the fight.

HOW TO TH I NK LI KE A SC I ENTI ST

ALGORITHM

WHAT DOES THE PROCESS OF PUBLICATION LOOK LIKE?

LESSON

According to the information and analytics company Elsevier, some 2.5 million scientific articles are published annually. The best go through a rigorous process that, all told, can take months or even years. Here’s the process, distilled.

Communicate with clarity and nuance

The most earth-shattering research findings won’t make a dent if scientists can’t share their results in ways that resonate. Here’s how scientists think about it—whether they’re publishing their findings in the most respected journals or telling the story of their work to the rest of us.

STEP 1

Come up with a great question.

STEP 2

Do the research and analyze the results.

CASE STUDY

STEP 3

Decide on your audience, and write up your results.

WHEN SEEING IS BELIEVING In 2017, Susan Cheng, MD, MPH, MMSc, was studying risk factors for stroke. Her research suggested something important: High blood pressure was significantly more likely to play a role in strokes in Black people than white people. She didn’t want this crucial piece of information to get lost, so she aimed high. She submitted the findings to the prestigious New England Journal of Medicine, the world’s most influential medical journal.

STEP 4

Send to a publication for review.

STEP 5

Get your research reviewed by peers.

No Was it accepted?

Yes w/revisions Yes

STEP 6

Revise. Go to step 4.

PUBLICATION. Congratulations! Time to start again. Go to step 1.

Benedetto Cristofani

STEP 7

FALL 2021 | DISCOVERIES |

HOW TO TH I NK LI KE A SC I ENTI ST

LESSON 5

To make the findings stand out, she and her team transformed spreadsheets of numbers into a compelling and easy-tounderstand graphic. “We wanted the image to be as good as the infographics you get in The New York Times during election season,” she says. It worked: The findings were published in the letters section of a publication with 600,000 weekly readers. “We knew that this was an important message, and we knew that if doctors understood the contribution of high blood pressure to stroke for Black patients, they would likely put more effort into controlling it in Black patients at risk for stroke,” she says.

Q&A

TOUGH QUESTION

In many cases, scientific publications are so technical that only a handful of people understand them well. How can scientists explain their research to a wider audience without “dumbing it down”?

“I tell my trainees that if you want to increase your reach, you need to recognize that what you’re doing reflects your insight as one of the world’s leading experts in whatever topic you’re investigating. In other words, what may be obvious to you isn’t necessarily obvious to anybody else. So it’s important, first, to set up the problem in context: Why is it important? How is it relevant to human disease? Then, you’ve got to be able to tell a story. It takes a particular conscious effort—a stepping back from the minutiae of what you’re doing—to ask: ‘What is really vital about this, and how does it move the argument forward? Or how does it contradict some preconceived notion?’ The ability to communicate scientific findings clearly is difficult, but it distinguishes the very best stuff from the rest.” –Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute

| DISCOVERIESMAGAZINE.ORG

LESSON

Take the long view: Great science takes time

Viewed through the lens of history, science moves at a relative gallop. Smallpox, a disease that existed for at least 3,000 years and killed up to 30% of those infected, was eradicated through a two-decade, worldwide vaccination campaign that ended in 1980. Scarlet fever, the leading cause of death in children in the early 1900s, was all but gone by the 1950s in the United States, thanks to the development of antibiotics in the 1920s and ’30s. Those timelines can feel like an eternity if you’re the one waiting for a treatment, but the reality is that major progress in most fields rarely happens overnight. “It took a decade to put a man on the moon,” says Keith Black, MD. “Good work takes time.” CASE STUDY

FROM BRAIN TO BEDSIDE TO BENCH: AN INSIDER’S VIEW Jennifer Van Eyk, PhD, director of the Advanced Clinical Biosystems Research Institute, wanted to develop a diagnostic blood marker for traumatic brain injury. She knew it would be useful for diagnosing patients, including war veterans and children with severe conditions who temporarily need machines to support their heart and lungs. So she prepared herself for what she knew would be a years-long grind. First, Van Eyk, along with her collaborators, thought about who might benefit from such a marker, so

she identified a wide spectrum of patients who had some level of subclinical brain injury. Then, she and her team set out to find proteins that showed promise as a marker present uniquely in the blood. To do so, Van Eyk created an assay—a lab process that measures the presence of a blood protein—from scratch. “It’s not like there’s a magic pot where these assays just exist,” she says. “You have to develop each one, and it has to be consistent enough to run today, tomorrow and the next day,

COVID-19 COUNTERPOINT

ACTUALLY, WE CAN DO GREAT SCIENCE FAST, TOO Science is designed around careful, methodical processes, but COVID-19 showed us that, if the need is urgent enough, some processes can be fasttracked. For example, scientists compressed the vaccine development timeline by combining trials that would otherwise be split into three phases and run sequentially. Early investments in vaccine-development companies and manufacturing capacity helped make the eventual rollout smoother. Susan Cheng, MD, MPH, MMSc, whose lab is pursuing a mix of both COVID-19 and other projects, says the seriousness of the pandemic led her team to experiment in ways that helped them speed up some processes. “Instead of having one analyst working on a project, we might have two or three,” she says. While the changes require careful communication and collaboration, they also accelerate the initial research as well as parts of the publication-revision process. “We’ve adapted,” she says. “But we haven’t let up on our quality or rigor.” BIG PICTURE

Joey Guidone

SCIENCE EVOLVES

and get the same answer.” Over many iterations, the markers were taken up by a company that helped to winnow down the potential options to a handful of promising targets, which went through even more rigorous analysis with specific cohorts of certain categories of patients until Van Eyk found just what she needed. This process—developing the right technology and supporting years of work in the lab—requires millions of dollars. As a result, Van Eyk and her team must continue to pursue funding to keep the process moving, from grants to venture capital support that ensure flexibility to find markers for more than just traumatic brain injury. For projects like hers that have

significant commercial potential, there’s also the matter of securing intellectual property rights and finding the right company to manufacture, market and sell any products that result from the research. “We have to take so many different steps, and we need so many different skill sets—not all of which reside within a single lab group,” she says. “It takes a village, and we don’t always have a village.” The project is now being tested in clinical trials—12 years after Van Eyk began her search for a biomarker. But the payoff—if everything goes to plan—is that, someday, when someone shows up in the emergency room and doctors think the patient might have a traumatic brain injury, they can use the marker she developed to diagnose it.

Even the most highly regarded science in a given moment doesn’t always get it right. That doesn’t mean it’s shoddy or fraudulent, says David Underhill, PhD, chair of the Department of Biomedical Sciences. It might just mean that it wasn’t replicable in the ways people hoped or that the implications turned out not to be relevant. “That’s the nature of science,” he says. “But it also means it’s self-correcting.” By contrast, some scientists can toil in relative obscurity until the right moment arrives. One example? Hungarian-born biochemist Katalin Karikó, PhD, whose mRNA research had been mostly overlooked, recently became the basis of two of the most successful COVID-19 vaccines. (She partnered with Drew Weissman, MD, to develop the science behind the vaccines.) This process of reviving once-undervalued findings is another benefit of the scientific process, Underhill says. “We try to make work as impactful as we can, using a peer-review process to get it as correct as we can and, at the end of the day, science that’s particularly good leads people to refer to it, follow up on it and build on it,” he notes. “Good science holds up over time.”

FALL 2021 | DISCOVERIES |

FOLLOWING THEIR

HE RTS V

Major advances in the field of congenital heart disease have dramatically improved survival rates for babies born within the last 50 years— and outcomes are only improving. But many patients, like Steve Hynes, forgo treatment after they age out of pediatric cardiology, to devastating consequence. Cedars-Sinai’s pioneering congenital heart experts aim to close the treatment gap.

By CASSIE TOMLIN Photograph by JASON ELIAS

| DISCOVERIESMAGAZINE.ORG

Elevator mechanic Steve Hynes ignored his congenital heart condition for decades, leading to a health crisis.

teve Hynes and Rafi Perchuk were born about 9 miles and 50 years apart, each with errant veins burdening the beating of their hearts. Across time and space, the boys’ mothers suffered the same emotional whiplash when their firstborn sons turned blue in newborn nurseries, shock complicating overwhelming joy. In 1970, Hynes’ parents declined to put their infant through a surgery they were told carried a 50% chance of survival—consequently, over half a century, he deteriorated dangerously into heart failure. But in 2021, faced with a similar condition, Rafi’s doctors and nurses at Cedars-Sinai promised his mom that, under their care, her little boy would almost certainly thrive. The population living with congenital heart disease is more vast and varied than ever before: Babies with defects like Rafi’s are born daily, but the majority of patients in the U.S. are adults like Hynes. Even the existence of adult patients is a relatively new phenomenon—as recently as the 1980s, more severe diagnoses resulted in an almost definite death sentence for children. Now, thanks to surgical advances, new generations can survive to adulthood alongside doctors well equipped to treat their unique, lifetime needs. The challenge can be getting those adults to show up for care—a treatment gap that Cedars-Sinai physicians aim to close. “For the longest time, people thought of congenital heart problems as pediatric issues to be dealt with in childhood, but these conditions have important implications throughout a lifetime,” says Evan Zahn, MD, director of the Guerin Family Congenital Heart Program and the Division of Pediatric Cardiology. “You could’ve had a great heart surgery as a little boy or girl, but when you’re 50 and you’ve developed hypertension, it raises different problems.” The Smidt Heart Institute’s Rafi Perchuk’s heart Guerin Family Congenital condition was Heart Program is at the repaired and he is thriving, but 50 forefront of comprehensive years ago, the result care for all patients, from may not have been babies diagnosed in the womb so positive. to septuagenarians with complex medical histories and new-to-medicine maladies. The expert team, embedded in the largest and most venerated heart program on the West Coast, is uniquely prepared to offer anyone the full spectrum of interventional, open-heart, hybrid and minimally invasive procedures. Richard Kim, MD, a calm, warm, deeply experienced surgeon, joined Cedars-Sinai in

| DISCOVERIESMAGAZINE.ORG

“People thought of congenital heart problems as pediatric issues to be dealt with in childhood, but these conditions have important implications throughout a lifetime.” —Evan Zahn, MD, director of the Guerin Family Congenital Heart Program and the Division of Pediatric Cardiology

2020 from Children’s Hospital Los Angeles as the new director of Pediatric and Congenital Heart Surgery and surgical director of the Congenital Heart Program. Kim’s appointment expanded the program’s ability to offer the most advanced surgical options for the most complex cases on both ends of the age spectrum. In April 2021, on consecutive sunny days, Kim performed lifesaving open-heart surgeries: first on 4-day-old Rafi, and

next on Hynes, an adventurous 51-year-old elevator mechanic. Both patients went home within a week, their hearts repaired and open to bright futures.

A DIAGNOSIS

Dina Hovsepian’s pregnancy with Rafi was healthy and normal, outside of gestational diabetes in her second trimester and despite the COVID-19 pandemic. She had a “magical” delivery at Cedars-Sinai, with her husband and her sister by her side. Seven hours after Rafi was born, nurses noticed that he looked blue—a sign of lack of oxygen. Before the family could even process his arrival, they had to confront his diagnosis: total anomalous pulmonary venous return (TAPVR), a condition in which four major veins from the lungs drain to the wrong place in the heart, meaning the blood circulating in the body is never fully oxygenated. Without surgery, Rafi would not survive. Congenital heart disease is the most common birth defect— about 1 in 125 infants enters the world with a malformed vein, artery, valve or heart chamber impeding crucial blood flow. Such structural dysfunctions range from relatively easy-to-fix holes and leaks to complex and life-threatening problems requiring emergency surgery in infancy. Congenital heart disease manifests in so many ways that physicians won’t commit to the number of variations. A lot can go wrong as the heart forms from a single cell into a complex, eternally pumping muscle. “To really get a handle on the field, you have to have seen many patients for many years,” Kim says. Heart anomalies can be inherited but, for most patients, the cause of a congenital defect is unknown. About half of congenital heart diagnoses are considered “simple,” like patent ductus arteriosus (PDA), a hole that Zahn fixes with a minimally invasive procedure he developed. The other half are like TAPVR, requiring painstakingly precise repair by a highly experienced surgeon.

THE EXPERT SOLUTION

Despite the distressing, draining news that her baby would need open-heart surgery, Hovsepian was confident in the staff, who “swooned” over Rafi and “did everything they could” to explain his condition and what to expect. “The nurses took care of Rafi like he was their own baby, and because of how they looked after us as brand-new parents, we could trust the process even more,” she says. On a day of head-spinning firsts for Hovsepian and family, Kim scrubbed in as he has thousands of times before. He opened Rafi’s inches-long breastbone to access his strawberry-sized heart. He connected Rafi to a heart-lung machine, which took over the work of those organs. The doctor then cooled Rafi to below 65 degrees to induce hypothermia, so that his cells only needed a minimal amount of oxygen. He slowed Rafi’s heartbeat

to a stop and rerouted the tiny, misdirected veins to the right place using a suture finer than a human hair. He patched a hole using Rafi’s own heart tissue. The repair finished, he rewarmed Rafi’s body. Slowly, the infant’s heart restarted on its own, and he was disconnected from the machine. The boy recovered well and, four days later, he went home with some Tylenol and instructions for his parents to scoop him up from underneath to protect his healing sternum when holding him. Rafi and his family received all their care under one roof— from delivery to discharge. And though he is expected to recover fully and enjoy a normal, healthy childhood, he’ll need monitoring forever. For Rafi, being born into Cedars-Sinai’s program will avoid an all-too-common pitfall for many congenital heart patients: They feel fine when they age out of pediatrics and stop seeing a doctor, only to return years later with accumulated conditions. “After many of the things we do for children, they will need continuous monitoring,” Kim says. “Rafi’s problem may be completely solved, but he will still need to be followed for life.”

KEEPING PATIENTS CLOSE

In 1970, the year Hynes was born, only 325,000 adults in the United States had congenital heart disease diagnoses. Today, thanks to advances that have radically extended lifespans for such patients, Hynes is one of about 1.3 million. Yet 75% of adults who were born with a congenital heart defect are not under treatment by a specialized cardiologist. Though adult patients live significantly longer when they’re cared for by such

THE FUTURE OF PERSONALIZED CARE In their quest to treat patients for life, Guerin Family Congenital Heart Program leaders are studying ways to reduce the need for continued procedures and improve targeted care. Zahn and a team of biomedical engineers are developing a stent that can grow with a baby—allowing doctors to repair a narrowed pulmonary artery that won’t ever need to be replaced as arteries grow with the body. He expects to start a clinical trial in babies this year. “The goal is a stent that can be put into a baby as small as a newborn and

ultimately enlarged up to a guy my size,” he says. Kim has long been a principal investigator on a National Institutes of Health-funded, multicenter study examining genome sequences of children with congenital heart disease. His goal is to use genetic information to personalize care, and he hopes eventually to tailor operations to best suit a patient’s genes. “We would like to be able to say, based on your genetics, which therapies may be more effective or which medications would work best,” Kim says. FALL 2021 | DISCOVERIES |

experts, there are only a tenth as many adult congenital heart physicians as there are pediatric heart doctors. Cedars-Sinai physicians have the advantage of managing a patient’s transition from childhood care to adult care in-house, and they also make it part of their mission to keep patients engaged. The strategy is well-timed transparency, says Ruchira Garg, MD, director of Congenital Noninvasive Cardiology, who is certified in treating both adult and pediatric patients. “It used to be that once you turned 18 or 20, your pediatric cardiologist couldn’t see you anymore, and patients went out into the wild,” Garg says. “I start educating teens over a few years so they have a robust understanding of what they’re living with and to empower them to be partners in their care.” Without monitoring and guidance, patients often experience slow and steady decline, a consequence of unchecked scarring after procedures, general aging and the collision of acquired heart disease with heart function that’s not totally normal at baseline. The preventive approach aims to spare adults from falling ill and requiring repeated procedures. In addition to screening for diabetes and helping patients control cholesterol and blood pressure, physicians must consider the complex challenges facing adult patients. “You have to start addressing all these other factors that just

aren’t there in kids: substance abuse, emotional trauma of living with repeated procedures in childhood, having their own families to support and take care of, maintaining a job,” Garg says. “The realities of life come into play.”

THE PULSE OF SURGICAL PROGRESS

1953

The oldest people living with congenital heart disease underwent procedures that set the standards of care for new generations. “Patients in the 1960s and 1970s were the first brave people to undergo these initial surgical repairs that have led to improved outcomes for patients today,” says Rose Tompkins, MD, associate director of the Smidt Heart Institute’s Guerin Family Congenital Heart Program. “They are living proof and living history.” Here is a brief timeline of advances in congenital heart surgery.

1938

Seven-year-old Lorraine Sweeney undergoes the first surgical repair of a heart defect (PDA). She became a great-grandmother and lived to age 89.

| DISCOVERIESMAGAZINE.ORG

1944

A DELAYED FIX

Hynes is both a textbook-typical and exceptionally rare adult congenital heart patient: typical because he hadn’t seen a cardiologist in years, and rare because not many people of his age with his condition are still alive. Hynes has partial anomalous pulmonary venous return— similar to Rafi’s condition, but less severe, with only two veins draining to the wrong place. Additionally, his heart is on the right side of his chest. As a kid, his parents took him for regular checkups. His heart function didn’t get better or worse, and it didn’t keep him from long summer evenings of street hockey in his family’s Redondo Beach, Calif., cul-de-sac or joining the wrestling team in high school. But left to manage his own healthcare after graduation, he stopped seeing a doctor. “My life was so normal that I forgot about it,” he says.

First successful use of the heart-lung machine, in the repair of atrial septal defect (ASD)—a hole in the wall between two chambers of the heart—inspiring a decade of advances in open-heart surgery.

Alfred Blalock, MD, Helen Taussig, MD, and Vivien Thomas implement a shunt as a temporary fix for artery and valve problems associated with tetralogy of Fallot, a critical defect. Their work marks an escalation in surgical intervention.

1968

The Fontan procedure begins to expand life expectancy for children with hypoplastic left heart syndrome (HLHS), in which only one ventricle is functional, and who had previously not survived past 1 year old.

1960s

Interventional procedures advance; cardiac catheterization gains momentum to treat congenital heart defects like PDA and ASD, as well as other heart disease.

As a teen, Hynes developed “knucklehead” habits—drinking, smoking, drugs—that persisted into adulthood. He built a good career but also partied a lot—until his heart condition caught up with him in summer 2020, when he had to catch his breath on the way up 15 stairs to his home in Canoga Park, Calif. In the back of his mind, his heart condition lingered. He had good health insurance and knew he should seek an expert opinion. In June, at his first appointment at the Smidt Heart Institute, Garg immediately began to untangle the situation. Hynes’ heart was functioning poorly after a lifetime of extra work and the injury of substance abuse. The right side was enlarged, he had pulmonary hypertension and his heart rhythm was off. She told him: “This is not your problem to worry about anymore. It’s our problem. You’re in our hands now.” “Whatever you tell me to do, I’m going to do,” he replied. It started with habits—he quit drinking a fifth of rum a day, changed his diet and stopped smoking. Garg and colleagues put him on “aggressive” heart failure medications, and he underwent a minimally invasive procedure to fix the heart rhythm. Finally, he was ready for more complex surgery. Kim performed a variation on the process he did with Rafi, this time creating a hole in Hynes’ heart and constructing a

1980s

The Norwood procedure further advances treatment of HLHS, and patients begin to survive into adulthood.

1975

The first successful arterial switch procedure, to correct the position of the heart’s two main arteries, is performed in Brazil on a 42-day-old baby.

pathway for the blood in his veins to circulate to the correct side. Five hours later, Hynes woke up. “You made it,” he mused to himself. “Time to recover.”

A HOPEFUL HORIZON

About 15 years ago, Hynes quit his job and drove east for six weeks to Knoxville, Tenn., fishing, camping and golfing along the way. He marveled at the Badlands, where he helped an old cowboy fix up his Jeep. That’s the kind of stuff he’s looking forward to now—making the second half of his life better than the front end. He feels like he owes it to his heart team. “I’m finally going to get to live the life I was meant to live,” he says. After two additional procedures, Hynes is back at work. He loves troubleshooting with his union buddies and breathing in the ocean air on his beach city service route. Rafi’s parents hope that when he reaches Hynes’ age, he’ll be happy and healthy, accomplished and kind, and that he’s well taken care of by physicians who encourage him to stay well. “What we strive to do is find things before they become big problems,” Garg says. “We can intervene along the way and help people live long and full lives.”

2000

2019

The first minimally invasive heart valve replacement by catheter is performed.

Zahn’s research leads to Food and Drug Administration approval of the first implantable device, by catheter, to treat PDA in newborns. Cedars-Sinai continues to study its effectiveness compared to other procedures.

2010s

Advanced 3D modeling and imaging allow surgeons to prepare and practice for complex procedures.

FALL 2021 | DISCOVERIES |

AL O NE ( (

TOGETHER

WHEN A PERSONAL HEALTH CRISIS LIKE CANCER CLASHES WITH A PANDEMIC, AN OFTEN-ISOLATING DISEASE CAN BECOME EVEN MORE CONFINING. THOSE WHO ENDURED CANCER IN 2020 EMERGED WITH POWERFUL PERSPECTIVES THAT CAN HELP ANYONE FACE HARD TIMES. By NICOLE LEVINE Illustration by RICHARD BORGE

| DISCOVERIESMAGAZINE.ORG

Kaelyn Garvine doesn’t want to be treated with kid gloves because of her melanoma.

| DISCOVERIESMAGAZINE.ORG

pleasures like lingering over a steaming latte at a bustling café, laughing with a crowd at a movie and singing along in the electric energy of a live concert disappeared. Jobs went remote or went away, while essential workers masked up and reported for duty. The pandemic forced everyone to make sometimes challenging changes, says Arash Asher, MD, director of Cancer Rehabilitation and Survivorship at the Samuel Oschin Comprehensive Cancer Institute. Those whose cancer diagnoses collided with a worldwide health crisis faced all those same pressures—on top of chemotherapy, surgeries and a host of other demands. Examining how they endured this time illuminates ways to cope with unexpected and lasting hardships. “If there’s anything we can all take away—not just our patients but all of us—from this traumatic experience, it’s some sense of perspective,” Asher says. “It thrust a life lesson on us, and a reminder of the things that are important and what our priorities are. We all got a little taste of what cancer patients go through. We had to contend with our mortality and the unknown, facing the fears that come with going through a serious medical circumstance.”

THE PERSONAL VS. THE PANDEMIC he pandemic amplified stress and loneliness for everyone, but studies found that cancer patients were particularly impacted. About half of respondents to an American Cancer Society survey reported that the pandemic affected their mental and emotional health. Cedars-Sinai patients are screened for depression, and during the pandemic those screenings more frequently prompted discussions about coping strategies and referrals to mental health specialists. These trends transformed appointments for patients and their oncologists, says Omid Hamid, MD, director of the Melanoma Program at Cedars-Sinai and chief of Translational Research and Immunotherapy at The Angeles Clinic and Research Institute. “You can have lots of tunnel vision during a patient visit because of the gravity of the diagnosis you’re dealing with,” Hamid says. “That’s changed. We spend much more time talking about the entirety of their current situation. Not a visit goes on without a nod toward the risk of COVID-19, whether physical, emotional or mental.” The necessities of physical distancing made it harder for cancer patients to seek help, comfort, and support from friends and neighbors. Much of the advice typically offered to cancer patients—like enjoying a weekday movie or brunch when crowds

Max Gerber

n an endless serpentine of cars idling around Dodger Stadium, Marcine Rossen is clutching the wheel of her Volvo hardtop convertible. But she’s not headed to a baseball game: For more than two hours, she’s been waiting to get to the front of the line and receive her first dose of the COVID-19 vaccine. She jokes that it’s a little like being stuck on the 405 freeway, but with no exits in sight. “The only way out of it was to go through it,” she says. Over the past year, Rossen, 75, has worked her way through a to-do list nobody wants: She started radiation therapy to treat breast cancer within days of the much-awaited shot. Her diagnosis came in July 2020, followed by surgery in August, then chemotherapy and radiation in the following months. “With cancer and with the pandemic, you just keep putting one foot in front of the other,” she says. “You keep moving forward. You hope you can get through it.” COVID-19 rapidly forced changes to everyday life. Simple

“Hearing that my family is interested and that they care has been so important. It reminds me that I’m so grateful for all I do have.” –Marcine Rossen, cancer patient

are thinner—became moot, says Jan-Kees van der Gaag, MSW. “When you’re diagnosed with cancer, your world suddenly becomes so small, and part of coping is finding ways to make your world a little bit bigger,” says van der Gaag, who works as a clinical social work supervisor for the Cedars-Sinai Cancer Patient and Family Support Program. “Cancer can be dehumanizing in many ways. Physical touch and physical presence are very powerful. We lost those with COVID-19.” Kaelyn Garvine, 43, lost her two go-to stress relievers. The pandemic halted her softball activities, an outlet for exercise and bonding with teammates since her teen years. And the melanoma on her foot and leg made her beloved beach walks impossible. In addition to losing those activities, the worry her loved ones expressed over her diagnosis coupled with the threat of COVID-19 became extra obstacles. “People treat you with kid gloves,” she says. “I’m not more likely to catch COVID-19 than anyone else. It is frustrating when everyone thinks they know what’s best for you in these difficult times.”

LESSONS EARNED ossen learned from her experience at Dodger Stadium that sometimes the only way out of a difficult situation is through it. It wasn’t the only wisdom she and other patients earned through 2020 and 2021. For others, making new connections—with humans or animals—brought much-needed relief. When no one could visit her Mar Vista home, Rossen counted on video visits with her 36-year-old nephew, Josh, in Hawaii, often with his 6-year-old daughter. Chatting about his work as a lifeguard offered a window into a life filled with surf, sand and laughter. “It helps just to be asked how I’m doing,” she says. “Just hearing that my family is interested and that they care has been so important. It reminds me that I’m so very grateful for all I do have.” Garvine joined the thousands who found furry friends during

the pandemic—pet adoption soared 15% in 2020, according to Shelter Animals Count, an organization that tracks shelter and rescue activity. She rescued a white pit bull terrier named Brian, whose sweet disposition has made him good company. “Now instead of asking me about my cancer, my friends ask me what new thing Brian is up to,” she says. Mindfulness, which focuses on staying in the present moment, is a recognized stress reducer. Van der Gaag says patients found it especially useful during the pandemic, often turning to mobile phone apps to help guide their budding mindfulness habits. “It’s normal to ruminate when you’re dealing with a crisis,” he says. “Often we will look at past actions and try to guess if we could have changed our present if we had done something differently.” These lessons don’t just apply to life with cancer: Trust in science, kindness to ourselves, connecting and staying present are all valuable tools for coping through adversity. “We found that some of our cancer patients coped with the challenges of the pandemic quite well because they had been going through treatment for some time,” Asher says. “I think we’ve all gained important perspective living through the pandemic, and we can carry that forward with us.”

UNEXPECTED GIFTS urviving the pandemic brought its share of hardships but also delivered an opportunity for reexamination, resulting in some potentially lasting benefits. While telemedicine isn’t new, COVID-19 was a catalyst for embracing and expanding it. “You cannot underestimate the value of telemedicine,” Hamid says. “Because of the pandemic, we’ve increased the capacity for patients to be seen, ask follow-up questions and get much of their care without leaving their homes. It also allows patients who live at great distances to obtain consultations and expert opinions on their care more conveniently.” Cedars-Sinai Cancer also opened its support groups to online video platforms, allowing participation from all over the country. The team is working on a hybrid model for the future that welcomes in-person support as well as remote access. Some experts in infectious disease had been predicting a pandemic would eventually strike. However, few were braced for how a pandemic of this enormity—claiming more than 4 million people worldwide—would change lives. The magnitude of the shared experience can drastically adjust people’s thinking. Asher sees that shift as becoming more centered on service as a way to create meaning. “As Dr. Viktor Frankl compels us in his seminal work, Man’s Search for Meaning, we can look at all the pandemic has taken away and say there’s no meaning in this,” Asher says. “We could react to the situation without having any sense of responsibility to uplift, improve and contribute. Or we can choose to ask what does life expect of me, and that turns our thought process toward what is meaningful.” FALL 2021 | DISCOVERIES |

Faculty News Fall 2021

Education

The Story Behind the Data

Moshe Arditi, MD— executive vice chair for Research in the Department of Pediatrics, director of the Infectious and Immunological Diseases Research Center and the Division of Pediatric Infectious Diseases, and the GUESS?/Fashion Industries Guild Chair in Community Child Health—was recognized by the cities of Encino and Los Angeles and the state of California for his critical research on COVID-19. He led a team of investigators in contributing to the most comprehensive study of multisystem inflammatory syndrome in children, funded by the National Institutes of Health.

Al Cuizon

How one graduate student is applying her creative abilities to healthcare delivery By ROSANNA TURNER Christine Easterling was born at Cedars-Sinai. But growing up in Los Angeles, she set her sights on working in Hollywood, not healthcare. “When I was a kid, I could recite movies, like Adventures in Babysitting and Wayne’s World, line by line,” Easterling says. “My parents would say to me, ‘Why don’t you remember math the way you remember movies?’” Easterling never imagined that she’d end up studying the connections between numbers and the stories behind them while earning a master’s in Health Delivery Science (MHDS)—and doing it where her own life story began. Easterling’s mother, Joyette Jagolino, was one of six nursing graduates who moved together from the Philippines to work at Cedars-Sinai in 1980. Jagolino, who retired in 2020 after 40 years at Cedars-Sinai, always wanted her daughter to become a nurse, but Easterling was more interested in pursuing a creative field. After graduating from college, she became a television producer, working mostly on unscripted and documentary shows in L.A. Then, in 2007, the Writers Guild of America strike halted production on many shows and Easterling was offered a position in Hong Kong with an L.A.-based apparel company. She lived in Asia for the next decade, working in China, Thailand, Indonesia and Sri Lanka. (continued on page 47)

Francesco Boin, MD, has been named the Cedars-Sinai Chair in Rheumatology. A world-renowned autoimmune disease researcher, he joined Cedars-Sinai in 2020 as director of the Division of Rheumatology and director of the Scleroderma Program at the Kao Autoimmunity Institute. He was most recently founding director of the Scleroderma Center at the University of California, San Francisco.

Easterling drew on her TV background for her master’s degree.

Peng-Sheng Chen, MD, senior cardiologist in the Department of Cardiology and the Smidt Heart Institute, has been named the Burns

FALL 2021 | DISCOVERIES |

Faculty News

and Allen Chair in Cardiology Research. He joined Cedars-Sinai in 2020 from the Indiana University School of Medicine, where he was chief of the Division of Cardiology and director of the Krannert Institute of Cardiology. Odelia Cooper, MD, director of the Clinical and Translational Research Center, has been named presidentelect of the Association of Program Directors in Endocrinology, Diabetes and Metabolism. The association supports initiatives in education, research and patient care, and advocates for post-graduate endocrine training programs. Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle, and the Warschaw, Robertson, Law Families Chair in Prostate Cancer, has been elected to the American Society for Clinical Investigation, one of the nation’s oldest and most respected medical honor societies and publisher of the Journal of Clinical Investigation. Joel Geiderman, MD, co-chair of the Ruth and Harry Roman Emergency Department, was awarded a 2020 Alumni Humanitarian Award from the College of Liberal Arts & Sciences at the University of Illinois Urbana-Champaign. He was honored for his

contributions to emergency medicine and his educational work on the Holocaust, including service as vice chair of the U.S. Holocaust Memorial Museum in Washington, D.C. Hui Han, PhD, director of MR Engineering in the Biomedical Imaging Research Institute in the Department of Biomedical Sciences, has been elected secretary of the governing committee for the International Society for Magnetic Resonance in Medicine’s MR Engineering Study Group. Scott Irwin, MD, PhD, director of the Patient and Family Support Program for Cedars-Sinai Cancer, has been named a fellow of the American Psychosocial Oncology Society. Michelle S. Keller, PhD, MPH, assistant professor in the Department of Medicine, was selected to join the Junior Investigator Intensive Program in Deprescribing Research 2021–2022 cohort. The program is part of the National Institute on Agingfunded U.S. Deprescribing Research Network, which develops and disseminates evidence about the process of reducing or stopping medications for older adults. Jayoung Kim, PhD, professor of Surgery and Biomedical Sciences,

| CEDARS-SINAI.ORG/DISCOVERIES

received the Mentor Award from the Center for Women in Science, Engineering and Technology. She was honored for her work as president of the U.S.-based Korean American Women in Science and Engineering. Jason H. Moore, PhD, has joined Cedars-Sinai as founding chair of the new Department of Bioinformatics Sciences, which will support statistical, data management, computational and informatics research infrastructure across the medical enterprise. Moore was most recently the Edward Rose Professor of Informatics and director of the Institute for Biomedical Informatics at the Perelman School of Medicine at the University of Pennsylvania, where he also served as senior associate dean of Informatics and director of the Division of Informatics in the Department of Biostatistics, Epidemiology and Informatics at the medical school. He holds master’s degrees in human genetics and applied statistics and a doctorate in human genetics from the University of Michigan. Neurosurgery postdocs Clayton Mosher, PhD, and Juri Minxha, PhD, were awarded the Cedars-Sinai Bohdan (Danny) Malaniak Award for Excellence in Postdoctoral Research.

They were selected for the quality of the scientific content, originality and clarity of their presentations at a January 2021 virtual event. Both work in the laboratory of Ueli Rutishauser, PhD, director of Human Neurophysiology Research and the Board of Governors Chair in Neurosciences. Pooja Nawathe, MD, associate professor of Pediatrics, has been selected by the Society of Critical Care Medicine as a 2021 recipient of its Presidential Citation, which honors members who have made outstanding contributions to the organization. Nancy L. Sicotte, MD, chair of Department of Neurology and the Women’s Guild Distinguished Chair in Neurology, received a Hedwig van Ameringen Executive Leadership in Academic Medicine fellowship for 2020– 2021. The fellowship advances and sustains academic women leaders. Sicotte is the third Cedars-Sinai faculty member to be accepted into the highly selective program. Piotr Slomka, PhD, director of Innovation in Imaging in the Division of Artificial Intelligence in Medicine, received the 2020 William W. Parmley Young Author Achievement Award from the Journal of the American

College of Cardiology for his mentorship and research program at Cedars-Sinai. The award recognized his role as co-author of “Coronary 18F-Sodium Fluoride Uptake Predicts Outcomes in Patients with Coronary Artery Disease,” which was published in the journal in June 2020. Harmik J. Soukiasian, MD, vice chair of the Cedars-Sinai Department of Surgery and chief of the Division of Thoracic Surgery, has been named the Tawil Family Chair in Thoracic Surgery. Soukiasian’s skills in robotic thoracic surgery and CedarsSinai’s expanding expertise in the field inspired the Tawil family to create the new chair to support continuing innovation. Brennan Spiegel, MD, MSHS, director of Health Services Research, published the book VRx: How Virtual Therapeutics Will Revolutionize Medicine. Selected as a top science book of 2020 by Wired magazine, it summarizes research at Cedars-Sinai into the role virtual reality can have in managing a wide range of medical conditions. Dan Theodorescu, MD, PhD—director of Cedars-Sinai Cancer, PHASE ONE Foundation Distinguished Chair and director at the Samuel Oschin Comprehensive Cancer Institute—and a

(continued from page 45)

colleague at the University of Southern California were awarded the inaugural Virtual Cancer Center Director Award by the Department of Defense (DoD) to establish the Convergent Science Virtual Cancer Center, the only such award granted in the U.S. Theodorescu will serve as director of the new center. Experts at the virtual cancer center will guide emerging scholars from diverse science backgrounds and institutions to accelerate their research and careers. The DoD, Congressionally Directed

Medical Research Programs and Peer Reviewed Cancer Research Program will provide more than $12 million to the effort. Jennifer Van Eyk, PhD, director of the Advanced Clinical Biosystems Research Institute and the Erika J. Glazer Chair in Women’s Heart Health, received the 2020 President’s Award from the North American Section of the International Society of Heart Research. The award recognizes individuals who have made fundamental contributions to the organization.

YOU’VE READ OUR RESEARCH. NOW COME LEARN WITH US. Cedars-Sinai offers multiple accredited graduate degree programs: PhD in Biomedical Sciences: One of the most sought-after PhD programs in the U.S., it merges scientific and translational medicine curricula with mentoring to provide students with broad exposure to clinical medicine. Master’s Degree in Health Delivery Science (MHDS): This program is designed to prepare graduates for a successful career in emerging healthcare fields, including digital health science, mobile health, health technology assessment, big data analytics, performance improvement and health economics.

Master’s Degree in Magnetic Resonance in Medicine (MSMRM): This discovery program is focused on training graduate students to become leaders in the field of magnetic resonance as it is applied to clinical practice. National Institutes of Health-Funded Postdoctoral Training Programs: Cedars-Sinai mentors graduates with doctoral degrees from a wide range of scientific and biomedical disciplines, with the goal of optimizing their career prospects. These opportunities actively encourage postdoctoral students to pursue careers in academic medicine or other research-related areas.

In 2017, she and her family returned to L.A. and she got a job at Cedars-Sinai. She’s currently a lead administrative assistant for Capacity Management. In 2019, she decided to apply for the MHDS program. “In order to be a leader, to spark change and innovation, I needed to develop more quantitative skills. I wanted to get a better grasp on biostatistics and analyzing health data,” Easterling says. While many students in the MHDS program have a nursing or medical degree, Easterling was an outlier. But her creative abilities were an asset when it came to qualitative data, which is subjective and open to interpretation. Qualitative data typically involves looking at participants’ responses to questionnaires and identifying common themes. “The qualitative methods I was using were similar to what I used when working in documentary TV,” Easterling says. “When making a documentary, you start with curiosity, something you want to explore. Then, you have to figure out how to tell the story and make it resonate with the audience.” Along with her daily duties, Easterling volunteers with the Spiritual Care department to offer Reiki to patients. Reiki is a Japanese healing technique intended to promote relaxation, serenity and wellbeing in those who practice it. Easterling’s experience with Reiki informed her master’s program capstone project, which looked at the impact of Reiki on pain scores for female cancer patients at CedarsSinai. She used a mixed-methods approach for this project, using both quantitative and qualitative data. Celina Shirazipour, PhD, a research scientist in the Cancer Research

Center for Health Equity at CedarsSinai, says that the need for qualitative data can sometimes be overlooked in healthcare. “Many times in healthcare, people think about numbers—increases or decreases in biomarkers or patientreported outcomes, length of stay, etc.,” says Shirazipour, who was a mentor to Easterling during her capstone project. “However, what can be lost in all the numbers is the person: the patient, their experiences, their story.” Shirazipour says that qualitative research provides richness and depth, allowing investigators to hear from the patient and their loved ones in their own words, and make sure their needs are central to their care. “With Easterling’s capstone project, the pain scores gave us an overview of whether Reiki was improving an important health outcome,” Shirazipour says. “The qualitative data brought the Reiki experience to life. What is the pain experience like for patients? What does it feel like to receive or deliver Reiki? What complexities exist in trying to treat pain? Together, these built a compelling story for the value of Reiki.” Brennan Spiegel, MD, MSHS, director of the MHDS program, says that Easterling’s research on Reiki illustrates the importance of going “beyond the pill” in modern medicine. “Pharmacology has its time and place but patients also benefit when we augment traditional medical treatments with evidence-based, mind-body therapies,” Spiegel says. For Easterling, the beauty of qualitative research is that “it’s messy and sometimes chaotic,” she says. “After you’ve collected the data, the interesting part is determining the meaning behind the numbers and what we can do with the information.” FALL 2021 | DISCOVERIES |

A Look Back

Dr. George Berci, circa 1962, with his video bronchoscope invention, and in 2020

The Scope of a Life Turning 100 is a rare milestone—but George Berci, MD, has accumulated as many astonishing accomplishments as he has years. In March 2021, the pioneering surgeon—Cedars-Sinai’s senior director of surgical endoscopy and innovation research—celebrated a century of legendary life. During the Holocaust, the one-time violin prodigy was conscripted into forced labor in his native Hungary until he narrowly escaped. In 1950, he earned

| CEDARS-SINAI.ORG/DISCOVERIES

his medical degree and, a few years later, helped establish one of the first experimental surgery programs in Europe. In 1970, Cedars-Sinai recruited Berci to join the Department of Surgery, and he soon established the medical center’s first multidisciplinary endoscopic surgical division. (Endoscopic surgery uses an endoscope—a thin, flexible tube with a light and camera at the end.) Berci developed miniaturized instruments and cameras that revolutionized the field of minimally invasive surgery and continue

to influence nearly every surgical specialty. Today’s technology looks slightly more hospitable than Berci’s early inventions (see photo). And while he no longer treats patients, Berci still comes to work every week. His secret to longevity? “I get up very early,” he says. “I go through what I need to do for the day, eat two pieces of toast with a cup of tea, take a short walk or go to the gym, and then I am usually at work by 7 a.m.”

GET BACK TO YOUR DOCTOR YOUR HEALTH YOUR JOY bettertogether.health

#WeLoveAHealthyLA

CEDARS-SINAI NONPROFIT ORG. U.S. POSTAGE

PAID PERMIT NO. 22328

Cedars-Sinai 8700 Beverly Blvd., Room 2416 Los Angeles, Ca 90048

LOS ANGELES, CA

In This Issue 24 How to Think Like a Scientist

18 MEET

What are the practices and mindsets that help drive great science? Discoveries asked Cedars-Sinai researchers and experts to weigh in about the processes scientists use to shape their work and drive progress.

Transplant surgery trailblazer Irene Kim, MD, shares her vision for the Comprehensive Transplant Center she co-directs, and how she finds balance between her personal and professional responsibilities.

34 Following Their Hearts

22 THINK

People who, like Steve Hynes, are born with congenital heart disease are living longer than ever—as long as they don’t skip out on care. How can physicians keep them connected over a lifetime?

Life to the Fullest

Big Questions About ‘Long COVID’ Investigators studying the disease outline the mysteries they’re trying to solve about the lingering and sometimes incapacitating impact of “long COVID.”

40 Alone Together

Physical distancing made it difficult for patients with cancer to seek support, but many emerged from the pandemic with a new perspective and new connections.

PUB_DISCF21