A Memory Expert Looks to the Future
A Heart Valve Revolution
Lessons for the Next Pandemic
P. 18
P. 28
P. 20
CEDARS-SINAI
SUMMER 2022
THE NEW LUNG CANCER LANDSCAPE Public health efforts and scientific advances have led to a significant drop in lung cancer deaths, but researchers are still searching for cures for the No. 1 cancer scourge P. 22
Cedars-Sinai
Shlomo Melmed, MB, ChB Jennifer Fagen
EXECUTIVE VICE PRESIDENT OF ACADEMIC AFFAIRS AND DEAN OF MEDICAL FACULTY EXECUTIVE DIRECTOR, BRAND STRATEGY AND CREATIVE SERVICES
Laura Grunberger Sarah Spivack LaRosa ASSOCIATE EDITORS Cassie Tomlin and Nicole Levine PROJECT MANAGER Karen Link DESIGN Robert F. Parsons for Seven Elm/sevenelm.com STAFF WRITERS Victoria Pelham and Rosanna Turner CONTRIBUTING WRITER Carrie St. Michel EDITOR IN CHIEF
SENIOR EDITOR
CEDARS-SINAI DISCOVERIES
© 2022 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, your 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 is a national leader in providing highquality, 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, CedarsSinai 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.
DISCOVERIESMAGAZINE.ORG
CEDARS-SINAI MAINTAINS THE 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.
SUMMER 2022
Contents
“ Anyone with lungs can get lung cancer.” Di’Ann Smith
MISHA GRAVENOR
The New Lung Cancer Landscape, p. 22
DISCOVERIES |
1
More Ways to Connect with Discoveries Discoveries magazine articles live online, too, and now you can have them sent directly to your inbox. Soon, you will have even more access to compelling stories about research at Cedars-Sinai and healthcare in our Southern California community. We want to connect you to the content that interests you most. If you’d like to receive email articles highlighting patient care, research innovations, breakthrough medicine or Cedars-Sinai’s lifesaving work in our community, scan the QR code below.
Thank you, and we hope to see you at cedars-sinai.org soon. The Discoveries editorial team groupeditorial@cshs.org
Contents Departments 5 NEWS & NOTES Genes drive women’s high blood pressure risk; bladder cancer breakthroughs; how individuals might respond differently to COVID-19 vaccines; resolving mysteries of a COVID-19-related pediatric condition; the wide world of cells; heart assist devices for those over 75; a model to predict ovarian cancer development; an MRIcompatible crib for the tiniest patients; scientific stunt doubles to classify cancers; and more. 18 MEET MEMORY MAKER Zaldy Tan, MD, MPH, a leading memory and geriatric medicine specialist, shares his vision for the future of dementia care.
20 LEARN LESSONS FROM A PANDEMIC COVID-19 dramatically altered the landscape of medicine. Two years on, Cedars-Sinai providers share how they came together to meet challenges and offer lasting lessons that could be applied to the next pandemic. 33 FACULTY NEWS A doctor’s education in trauma care began in college; now she’s teaching the next generation of healers. 36 A LOOK BACK Sarah Vasen, MD, was a pioneering physician who paved the way for women’s leadership at Cedars-Sinai.
28
Features
MARK LEIBOWITZ (PHOTO); ZARA PICKEN
22 The New Lung Cancer Landscape New therapies and a better understanding of lung cancer have led to fewer deaths, but researchers are still searching for cures for the No. 1 cancer scourge.
28 Keep On Ticking Dramatic advances in the field of minimally invasive heart valve replacement are extending and improving life for millions of previously untreatable patients. Cedars-Sinai physicians are seeking the next frontier. 7 COVER ILLUSTRATION
John W. Tomac
SUMMER 2022 | DISCOVERIES |
3
From the Dean
Seizing Momentum
L
“Our cutting-edge research into targeted, personalized therapies and our energized efforts to screen as many people as possible have propelled a momentous upswing in the fight against lung cancer.”
4 | DISCOVERIESMAGAZINE.ORG
os Angeles County’s smoking rates are now among the lowest in the nation’s urban areas. The decline in cigarette smoking is one of the most significant public health achievements of the last 30 years and has contributed to a striking reduction in lung cancer. Nevertheless, lung cancer still afflicts many Angelenos—even those who quit smoking years ago or who never smoked at all. Although cancer screening is an effective tool that we know saves lives, eligible Californians are among the least likely in the nation to be screened. We want to change that. Cedars-Sinai is assaulting the No. 1 cancer scourge on all fronts, as outlined in the cover story of this issue of Discoveries. Our cutting-edge research into targeted, personalized therapies and our energized efforts to screen as many people as possible have propelled a momentous upswing in the fight against lung cancer. Cedars-Sinai is launching a new lung cancer screening program. Simultaneously, we are creating a comprehensive screening strategy that will deploy mobile lung-screening units directly into areas that need them most. Also in this issue, we highlight our monumental achievements in surmounting another deadly foe: heart disease. Until recently, mortality rates from cardiovascular disease were gloomy. Although heart disease is still the leading global cause of death, we are seeing dramatic improvements in the United States, thanks to environmental factors like smoking cessation and revolutionary advances in medications and technology. We are proud of our longstanding commitment to cure heart disease. Over 60 years ago, our cardiologist Myron Prinzmetal, MD, pioneered groundbreak-
ing discoveries in hypertension and coronary artery disease while continuing to treat patients in our free clinic. Other trailblazers followed at Cedars-Sinai, including William Ganz, MD, a Holocaust survivor who went on to become a brilliant cardiac investigator, and Jeremy Swan, MD, a globally recognized cardiology leader, who together invented the revolutionary SwanGanz catheter, which has saved millions of lives worldwide. In keeping with our tradition of excellence, the Smidt Heart Institute is home to today’s giants in heart valve disease research and care. We are a leading center nationwide for transcatheter aortic valve replacement and are now pushing the boundaries for advancing minimally invasive repair and replacement of other valves. These inspiring achievements occur in tandem with our world-class heart programs, including transplantation. It is nothing short of miraculous each time a patient in a dire state, following a lifesaving heart or lung transplant, walks out of the hospital! I was a fledgling medical student at the University of Cape Town in 1967 when a teacher of mine, Christiaan Barnard, MB, ChB, performed the very first human heart transplant. How far we have come in those 55 years! Now, at Cedars-Sinai, I am honored to work alongside our remarkable experts at the nation’s leading heart transplant center. Your continued confidence and support are crucial to our ability to achieve our mission. Thank you for your enduring partnership.
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
ALISON SEIFFER
DNADriven Ups and Downs Women’s and men’s risk factors for high blood pressure may need different medical approaches. Research at Cedars-Sinai recently revealed that the
potential for high blood pressure—also known as hypertension—is more driven by genetics in women. “A woman with low genetic risk is less likely to develop hypertension than a man with low genetic risk,” says Susan Cheng, MD, MPH, MMSc, director of the Institute for Research on Healthy Aging at the Smidt Heart Institute and the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science. “Con-
versely, a woman with high genetic risk is more likely to develop hypertension than a man with high genetic risk.” For the study, Cheng and her team analyzed five decades of blood pressure and genotype data from more than 200,000 people. The results confirmed that sexspecific genetic risk traits are more associated with hypertension risk in women than in men—especially for the type of hypertension that starts early in life.
SUMMER 2022 | DISCOVERIES |
5
WHO’S WHO
3 QUESTIONS WITH
A pediatrics leader looks ahead
Ophir Klein, MD, PhD, is the inaugural executive director of Cedars-Sinai Guerin Children’s, a new initiative that will offer the full spectrum of pediatric specialties as well as a robust research program and training for future pediatricians. Guerin Children’s has been made possible by the generosity of the Shapell Guerin Family Foundation and its president, Vera Guerin, a longtime Cedars-Sinai supporter who currently serves as board chair of Cedars-Sinai Health System®. We asked Klein, the David and Meredith Kaplan Distinguished Chair in Children’s Health, what the future of pediatric care might look like. Is there an area of pediatrics that particularly requires the attention of the medical community in the next 10 years? One of
the most important areas
6 | DISCOVERIESMAGAZINE.ORG
for us to think about is the childhood roots of adult disease. Whether they’re infectious, environmental or societal, many of the impacts that children experience are
How do you think innovations in vaccine development and delivery will impact childhood diseases? Hope-
fully, one long-term result of the pandemic is that it will give a boost to vaccine development. This will not only help us deal with emerging diseases that can impact us locally but also address diseases in underdeveloped regions of the world. There are
many parts of the world where infectious disease plays a huge role in childhood illness and mortality. Part of our mission as clinician-scientists is to think globally; it’s an important part of medical research. What research avenues are you pursuing? My laboratory is interested in figuring out how organs form in the embryo and how they renew and regenerate in the adult. We call this field developmental and stem cell biology. We focus on craniofacial development and intestinal biology. These days, we’re interested in questions of cell identity and fate: How does a cell determine who it is and what it does? How is this identity malleable in the face of damage and regeneration? For example, in inflammatory bowel disease, we study the stem cells in the gut and try to understand how they sense there’s been an inflammatory flare and how their neighbors respond to these insults. If you understand how cells sense what’s going on around them and how they react to differences, then it enables you to think about how you could evoke different or better responses from them under conditions of damage. When you have inflammation, a neighboring cell’s response might be to further rev up, but it would be more helpful if it calmed the inflammation.
JAY WATSON
Ophir Klein
important in determining the course of their future health. There is intriguing evidence that early childhood events are at the root of several different adult illnesses. What we do is important not just for children but also for the adults they will become.
Patients with early-stage disease now have the option of a procedure called en bloc resection, which allows surgeons to remove the tumor in one piece.
ZARA PICKEN
Bladder Cancer Breakthroughs Cedars-Sinai is attacking bladder cancer through innovations in both the operating room and the laboratory. Patients with early-stage disease now have the option of a procedure called en bloc resection, which allows surgeons to remove the tumor in one piece. The technique involves looking inside the
bladder with a tiny camera and then removing the tumor by encircling it with a thin laser. The intact tissue makes it easier for pathologists to check whether the cancer is confined to the bladder lining or has invaded deeper into the organ, and it allows surgeons to determine whether any cancer has been left behind.
Meanwhile, for the 25% of patients whose malignancies invade bladder-wall muscle— increasing the danger of metastasis—Cedars-Sinai investigators have developed a means of predicting how bladder cancers respond to certain therapies. “My hypothesis was that if we looked at the expres-
sion of individual cells within the bladder tumor, we could develop more effective tools to guide treatment and perhaps even find novel targets for future therapies,” says Dan Theodorescu, MD, PhD, the PHASE ONE Foundation Distinguished Chair and director at the Samuel Oschin Comprehensive Cancer Institute and Cedars-Sinai Cancer. His team used singlenucleus RNA sequencing— which relies on isolated cell nuclei instead of whole tissue— to profile the genes expressed by each individual cell in aggressive muscle-invasive bladder cancers in 25 patients, map each cell’s position and study the cells’ interactions. RNA sequencing also enabled the study team to discover a previously unclassified type of cell in the bladder lining that expresses high levels of a protein associated with poor surgical outcomes.
SUMMER 2022 | DISCOVERIES |
7
COVID-19 RESEARCH
Individuals may respond differently to COVID-19 vaccines People should feel confident that their COVID-19 shots will keep them safe from serious illness. But overall, individual immunity is still a bit of a mystery: Who produces the strongest immune response? Who stays protected the longest—and what can this reveal about a person’s current and future health? Cedars-Sinai investigators are leading an ambitious five-year study that seeks to better define how and why people respond differently to COVID-19 vaccines. Ultimately, they hope to understand how factors such as age, sex and preexisting conditions influence immune response. Results could inform public health efforts to curb the spread of the virus and its variants—and improve long-term health across the population. The EMBARC study tracks immune measures, including antibody levels, in tens of thousands of Cedars-Sinai patients who have been vaccinated against COVID-19. Study leaders are working with community partners to recruit from schools, churches and neighborhood associations, and they are developing special outreach programs to ensure that the most vulnerable patients—such as those with immune-altering diseases—are represented.
Vaccine Response in IBD Patients When vaccines first became available for COVID-19, 70% of surveyed people with inflammatory bowel disease (IBD) expressed concerns about side effects. Crohn’s disease, ulcerative colitis and other forms of IBD are chronic conditions that occur when the intestinal immune system becomes overreactive, causing chronic diarrhea and other digestive symptoms. Because immune system malfunction is one possible cause of IBD— and patients are often treated with
8 | DISCOVERIESMAGAZINE.ORG
“We’re on a mission to expand our understanding as broadly as possible,” says 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. “This data will help us understand how we can build dynamic, long-lasting immunity as individuals and as communities. We aim to understand how we get out of the pandemic and how we survive and thrive beyond it.” Once published, the research will expand on insights gained from previous studies focused on healthcare workers, which found variations in immune response based on whether people had been infected with SARS-CoV-2, the virus that causes COVID-19, or had been previously inoculated for other infectious diseases. Study participants will have access to their own antibody-level measures as well as a database that could predict the strength of their immunity at different times following vaccination. “We’re taking the science back to our patients and our communities and developing tools to help with questions like: What is the outlook for myself and my family?” Cheng says.
immune-modifying medications— patients also worried that vaccines might not produce a sufficient immune response to protect them against COVID-19. But recent Cedars-Sinai research should ease their minds and digestive systems. The study revealed that IBD patients receiving immune-modifying therapies were not at risk of increased side effects from the Pfizer-BioNTech or Moderna COVID19 vaccines. More than 90% of IBD patients produced antibodies in response to COVID-19 vaccines, regardless of vaccine type and whether they were taking immune-
modifying medications, according to Gil Melmed, MD, director of Inflammatory Bowel Disease Clinical Research. However, IBD patients receiving the Johnson & Johnson vaccine developed significantly lower antibody levels than those receiving the two other vaccines. “The mRNA vaccines may have a more potent mechanism for inducing antibody response,” Melmed says of the Pfizer and Moderna vaccines. “And because they are delivered in two doses, rather than one dose like the Johnson & Johnson vaccine, they provide two immunological hits.”
COVID-19 IN KIDS A rare condition in pediatric COVID-19 patients can trigger an attack on vital organs weeks after infection. But an investigation led by Cedars-Sinai has uncovered potential predictors of the condition, called multisystem inflammatory syndrome in children (MIS-C), and could open avenues to better therapies. The scientists identified an array of pathways leading to MIS-C—along with proteins in the blood that could act as biomarkers to forecast the severity of the syndrome and help drive treatment decisions. Another recent study by CedarsSinai unmasked potential culprits contributing to MIS-C. The investigators found that children with the condition were unique because of differences in their T cells—immune cells that help the body fight infection. While most people have a diversity of T cell receptors, the study revealed that children with MIS-C likely have limited types of receptors or even just one type, suggesting an immune response to a special type of virus molecule called a “superantigen.” The findings shed new light on the mysteries of MIS-C.
ROB DOBI
Assessing Immunity
COVID-19 RESEARCH
N&N
“We’re taking the science ... and developing tools to help with questions like: What is the outlook for myself and my family?” Susan Cheng, MD, MPH, MMSc
SUMMER 2022 | DISCOVERIES |
9
There are more cells in the human body than stars in the Milky Way, each with a unique role in vital functions—from breathing to growing and eating. While the roughly 200 cell types work together, they follow different playbooks and routinely change casts. This cellular diversity is underappreciated, says Lali Medina-Kauwe, PhD, co-director of the Cancer Biology Program. “Structures are organized very intricately in and around cells, supporting all of the travel and various processes underway,” she says. Here are a few of the most fascinating cellular factoids.
While the roughly 200 cell types work together, they follow different playbooks and routinely change casts. 10 | DISCOVERIESMAGAZINE.ORG
CLEANUP CREW
Macrophages
LONG-DISTANCE RUNNERS
Neurons
RENEWABLE RESOURCE
Skin Cells
FREQUENT FLYERS
Red Blood Cells
TALENT DEVELOPMENT
Stem Cells
Macrophages are the body’s biggest eaters. They overwhelm and kill off bacteria and then clear dead cells and tissue debris. If overactivated, though, macrophages can trigger inflammatory disease and cancer growth. “They can be heroes or villains,” says Cedars-Sinai immunologist Helen Goodridge, PhD, who notes that macrophages are one of her favorite cells.
Neurons are the longest cells, with the lengthiest stretching nearly 5 feet down the spinal cord. Aided by motor proteins, these nerve cells transmit electrochemical messages that create movement, thought and sensations, including pain. They go the distance in age, too: Brain neurons can last an entire human lifespan and, theoretically, even longer. Compare that to the lifespan of heavily worked gut epithelial cells (three to five days) or pancreatic cells (one year).
Skin is constantly shedding and being replenished. The human body sloughs off 200 million dead cells from the skin’s outer layer every hour (almost 5 billion a day), replacing the skin entirely every 40 to 56 days.
About 70% of the human body’s cells—25 trillion—are red blood cells, or erythrocytes, making them the most common. That vast supply is critical to life: Tiny erythrocytes continuously ferry oxygen from the lungs throughout the whole body. The hemoglobin protein inside these cells is what paints blood its trademark red.
Found in embryonic and certain adult tissues, stem cells have not yet specialized. These prolific cells are at the heart of regenerative medicine, with their potential to be manipulated into immune, bone, skin, nerve or muscle cells. There is evidence that, in certain circumstances, just one hematopoietic stem cell in the bone marrow could regenerate and sustain an individual’s entire blood supply, including red blood cells and more than a dozen types of immune cells, Goodridge notes.
MARC ROSENTHAL
The Wide World of Cells
COMMUNITY
Caroline Carbajal, a community health worker with Cedars-Sinai’s Community Connect Program, makes weekly house calls to patients.
RACHAEL PORTER
Beyond the Exam Room For more than three months, Caroline Carbajal made weekly house calls to one of her patients: a retired 76-yearold man who had been experiencing panic attacks and increased blood pressure. Her visits revealed that he was also straining to manage mounting bills and facing eviction from his L.A. apartment. Carbajal isn’t a doctor. She is a community health worker employed by CedarsSinai as part of its Community Connect Program. The effort is an innovative response to a growing body of research demonstrating that fundamental life challenges—such as struggles related to housing, food, finances, transportation, substance use or mental illness—have an enormous impact on an individual’s health.
Identifying and addressing social determinants of health is the cornerstone of the Community Connect Program, which aims to screen every Cedars-Sinai patient for 13 social risk factors, says Katie Hren, LCSW, MPH, the program’s manager. When screenings uncover health-related social needs, social workers and nurse care coordinators consult an electronic referral platform powered by findhelp.org to match patients with support services. “It’s important for treatment teams to be aware of health-related social needs that patients are experiencing because these factors play a pivotal role in one’s health,” Hren says. “Armed with this information, caregivers can provide comprehensive, whole-person care.”
Carbajal’s work is part of a Community Connect Program pilot initiative evaluating the effectiveness of assigning community health workers like herself to vulnerable patients to connect them with long-term assistance. Ultimately, Carbajal helped establish a relationship between her patient and two local nonprofits that provide ongoing food assistance as well as mental health and financial services. As a result, he avoided eviction and paid his bills, and his panic attacks subsided and blood pressure stabilized. As a thank you, the man gave Carbajal a bow-accented houseplant. She pointed out an even better gift for them both: “He learned how to advocate for himself.”
SUMMER 2022 | DISCOVERIES |
11
Heartfelt Support
Heart assist devices underused in older patients For patients with heart failure who are unable to undergo heart transplantation, cardiac surgeons sometimes turn to mechanical left ventricular assist devices (LVADs) to get the blood flowing properly. Patients over age 75 who are otherwise healthy should be provided the option more often than they are, according to a Smidt Heart Institute study. The research, conducted through the Interagency Registry for Mechanically Assisted Circulatory Support, reviewed national data from more than 24,000 patients who had LVADs implanted to treat advanced heart failure. “I’ve treated some patients in their late 70s who had previously been very active and, after getting their LVAD, sent me pictures of themselves resuming activities they once loved—like travel and sports,” says Dominic Emerson, MD, associate surgical director of Heart Transplant and Mechanical Circulatory Support in the Smidt Heart Institute. Emerson served as lead author of the research.
12 | DISCOVERIESMAGAZINE.ORG
Fear of complications such as stroke, bleeding and infection has made some physicians wary of suggesting LVADs for elderly patients. But it’s time to reevaluate who might benefit from the devices, notes Joanna Chikwe, MD, founding chair of the institute’s Department of Cardiac Surgery and the Irina and George Schaeffer Distinguished Chair in Cardiac Surgery in honor of Alfredo Trento, MD. “For many patients with advanced heart failure, newer-generation LVADs are transformational,” she says. These LVADs are smaller than older models—half the size of a fist, rather than the previous dinner-plate dimensions—and use new technology to reduce blood clots and infection. The researchers found that patients receiving these newer LVADs experienced fewer device failures, less blood clotting within the device, and lower rates of infection and stroke than patients with previous-generation devices. Patients older than 75 even experienced fewer complications than their younger counterparts.
A new clinic for youth who are questioning their gender or experiencing gender dysphoria—the distress caused when a person’s biological sex does not align with their true gender identity— has opened at Cedars-Sinai. The Pediatric and Adolescent Gender Wellness Clinic is overseen by pediatrician Paria Hassouri, MD, a specialist in the field. The clinic helps youth and their parents by providing resources and support to navigate options such as medical transition or blocking puberty. This includes social support—especially for younger patients who have not reached puberty but feel gender fluid. “My advice to parents is to not hesitate or be scared about making that first appointment with someone who specializes in genderdiverse youth,” Hassouri says. “That first conversation is just about gathering information, which makes all the difference for families.” Once a patient turns 18, their care is transferred to physicians at Cedars-Sinai who specialize in adult gender wellness, including, if appropriate, therapeutic transitions.
GWEN KERAVAL
GENDER CLINIC OPEN
Cancer Prognosticator
MELINDA BECK
Scientists aim to predict ovarian cancer risk
“What if we could predict how serious the cancer would be—or if it will develop at all?” Clive Svendsen, PhD
Everyone has BRCA genes. They typically protect against cancer, but some people inherit mutated versions of the genes that increase their cancer risk. Women with these genetic changes are at greater risk of breast and ovarian cancer. Some women who discover they have BRCA mutations choose to have riskreducing surgery, removing their breast tissue or ovaries and fallopian tubes. They can’t know for certain whether they will get cancer, so they must weigh their risk and make the best decisions they can. “But what if we could predict how serious the cancer would be—or if it will develop at all?” says Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine. The seeds of ovarian cancer sprout in the fallopian tubes. Svendsen is using stem cell technology to take blood cells from women with BRCA mutations and reprogram them to make fallopian tubes in a culture dish. This process uses induced pluripotent stem cells (iPSCs). Human iPSCs are created by taking adult body cells “back in time” to create stem cells that can develop into any kind of human body cell. Because fallopian tube cells that are created from the iPSCs contain the DNA of the donor patient, they may develop cancer in the dish that is identical to what the woman would experience years or decades down the road. “We aim to use this model to predict individuals’ cancer development,” Svendsen says. “We also can test drugs on the cancerous tissue and determine which ones work.” The methodology could help monitor, prevent and treat a woman’s cancer— even determining drugs that could be taken prophylactically.
SUMMER 2022 | DISCOVERIES |
13
TECH CORNER
Rock-a-Bye MRI
“The earlier we can identify any risk in a child’s development, the earlier we can intervene to achieve better outcomes.” Wei Gao, PhD
14 | DISCOVERIESMAGAZINE.ORG
Making MRI Scans a Dream for Babies
Designed by Gao and his research team, the MRI-compatible crib resembles a bassinet attached to a rollable gurney. Gao’s main goal was to minimize the risk of disturbing a sleeping baby during transfer, thereby increasing the chances of a successful infant brain scan. The scanner bed of the MRI is raised up to the level of the crib prior to the scan. Made of a mesh-like fabric, the bassinet can be detached from its base using a series of clasps. The rest of the bassinet and the gurney are then rolled away from the MRI machine, leaving the baby on the scanner bed without experiencing any vertical or horizontal movement. “The prototype worked with the first baby we tested it on,” Gao says. “I was very happy.” Identifying Risk Factors in Infancy
Gao’s MRI-compatible crib, which is only available for research use, will be instrumental to the HEALthy Brain and Child Development Study. Following a large cohort of pregnant women and their children for at least 10 years, the National Institutes of Healthfunded study aims to map typical earlychildhood brain development and how risk factors such as parental substance use, impoverished environments and other social determinants of health may affect young brains. Gao sees a lot of potential in early intervention. “The first two years of a child’s development lay the foundation for their entire life,” Gao says. “The earlier we can identify any risk in a child’s development, the earlier we can intervene to achieve better outcomes.”
BILL POLLARD
Studying an infant’s brain can help predict the first few years of a child’s development—and the ripple effect this starting point will have on their adult life. “The brain grows the fastest during these years,” says Wei Gao, PhD, director of Neuroimaging Research at the Biomedical Imaging Research Institute at Cedars-Sinai. “Subtle deviations from a child’s normal developmental trajectory can have a butterfly effect down the road, potentially leading to various adult-onset or child-onset developmental disorders and disease.” The best way to map an infant’s brain in the first two years of development is by performing an MRI. But scanning babies’ brains in a research setting presents a major hurdle: To get a clear and accurate MRI scan, infants must be sleeping naturally and lying very still while on the scanner bed. “Even if we can get a baby to sleep naturally before the MRI, they often wake up, especially during the transition from the mother’s arms to the scanner bed,” Gao says. “Because this movement is disturbing for the baby, I thought, ‘Why not design an MRIcompatible crib?’”
NEW DISORDER DISCOVERED
Dr. Wei Gao and his research team designed this MRIcompatible crib.
A rare disorder that disrupts the motor skills of infants and teenagers has been discovered thanks to a research collaboration involving a Cedars-Sinai pediatric neurologist. Tyler Mark Pierson, MD, PhD, joined scientists from nearly 50 institutions worldwide to report on 31 children with this condition, known as HPDL deficiency. The genetic disorder occurs in two forms. The more severe form consists of lowerextremity spasticity associated with significant cognitive delays and frequent seizures. The milder type has a later onset and produces weakness and muscle stiffness in the legs of otherwise healthy teens. Both forms stem from abnormal activity in the cerebral cortex, which is responsible for functions such as thought, muscle tone and voluntary physical action. Pierson and his colleagues found that the study’s subjects had abnormalities in both copies of their human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene, which previously was not associated with any disease. Affected children inherit one mutation from each of their unaffected parents. The combined mutations decrease levels and activity of HPDL proteins, which are important for neurons’ cellular functioning.
SUMMER 2022 | DISCOVERIES |
15
Scientific Stunt Doubles Big data gets harnessed for personalized cancer treatments
Cedars-Sinai Cancer has joined with precision-medicine firm Tempus to design personalized cancer treatments. The partnership harnesses artificial intelligence and big data to create virtual replicas of patients’ DNA, RNA, proteins and other molecular information to help identify the most effective approach to overcoming each individual’s disease. By creating these “molecular twins,” scientists genetically classify cancer genes and proteins of particular tumors obtained from thousands of Cedars-Sinai patients to build a database that will advance research and treatments everywhere. “Molecular twins serve as scientific stunt doubles that are always in the lab, ready to identify the best current therapies and, perhaps, reveal important details of how a cancer will affect the patient,” says Dan Theodorescu, MD, PhD, the PHASE ONE Foundation Distinguished Chair and director at the Samuel Oschin Comprehensive Cancer Institute and Cedars-Sinai Cancer. The data—stripped of personal details to protect privacy— will offer insights into why some patients are resistant to certain therapies and also provide potential avenues to new treatments. Another aim is to remedy disparities in care.
“While there are success stories with targeted, precision treatments for cancer, they are limited today to only a few cancer types,” Theodorescu says. “Additionally, the research that leads to lifesaving breakthroughs often falls short among certain racial and ethnic groups. I hope that the molecular-twin platform will change that since it has the potential to analyze cancer disparities in vulnerable populations and possibly find solutions to closing the cancer health-equity gap by streamlining and reducing the complexity and cost of these tests.”
“Molecular twins serve as scientific stunt doubles that are always in the lab, ready to identify the best current therapies and, perhaps, reveal important details of how a cancer will affect the patient.”
ID on Idiopathic Fibrosis Mechanisms behind idiopathic pulmonary fibrosis (IPF), a dangerous disease that scars the lungs and impairs breathing, are being demystified by CedarsSinai investigators. The condi-
16 | DISCOVERIESMAGAZINE.ORG
tion affects more than 100,000 people in the U.S., with most patients dying within five years of diagnosis unless they receive a transplant. In normal lungs, type 2 alveolar epithelial cells (ATII) function as progenitor or stem cells, regenerating to support lung renewal and health. Meanwhile,
other stem cells support their ATII kin by secreting growth factors. But in IPF, these mechanisms are lost, leading to progressive scarring that disrupts the flow of oxygen into the bloodstream. To understand why, investigators created a mouse model of pulmonary fibrosis in which
they eliminated the growth hormone receptor. The results showed that mice without these receptors were more prone to developing fibrosis. These findings suggest that treatment with growth hormone receptors using a nanosize delivery mechanism may improve lung function.
MARK MATCHO
Dan Theodorescu, MD, PhD
JULIETTE BORDA
A Better Read on Blood Pressure in Pregnancy When the American Heart Association and American College of Cardiology updated their guidelines on blood pressure treatment and management in 2017, they left out a considerable swath of the population: pregnant women. “It’s because there wasn’t enough data on pregnancy to provide evidenceinformed recommendations,” says Natalie Bello, MD, MPH, director of Hypertension Research at the Smidt Heart Institute at Cedars-Sinai. “I’ve taken that to heart, and I’m trying to build a better knowledge base of the best protocols to follow for high blood pressure during pregnancy.” The United States has the highest rates of maternal morbidity and mortality compared to similarly wealthy countries. Cardiovascular disease is now the leading cause of death during pregnancy. Bello co-chairs a work group for the American College of Cardiology that focuses on cardio-obstetrics. The group seeks to expand scientific knowledge in the field, inform both cardiologists and obstetricians of the heart health needs of pregnant patients, and advocate for policy changes to help this population. A recent study she led, published in the Journal of the American Medical Association Network Open, found that applying a lower blood pressure threshold for hypertension allowed clinicians to better predict risk of preeclampsia (high blood pressure in pregnancy) and other adverse pregnancy outcomes. The study used electronic medical record data of women who delivered infants between 2009 and 2014 at a large regional health system. Blood pressure is measured as two values. The first measures pressure on blood
vessels when the heart beats, and the second measures pressure when the heart is relaxed. When applying a 130/80 mmHg threshold to diagnose hypertension—rather than the 140/90 mmHg traditionally used to define high blood pressure in pregnancy—the investigators found they could more accurately identify which women were likely to develop preeclampsia.
Hypertension treatment during pregnancy is approached with caution, as an adequate blood supply must flow to the placenta to nourish the developing fetus. “In pregnancy, we have to look out for both patients—the mom and the baby,” Bello says. “This warrants more testing, but our findings are a real signal that we can identify maternal risks without creating greater risk for babies.” This is one example, Bello says, of the need to expand the data about pregnancy to match what we know about adults who are not pregnant.
SUMMER 2022 | DISCOVERIES |
17
Meet
Memory Maker: Zaldy Tan By CASSIE TOMLIN There is no cure for Alzheimer’s disease, the leading cause of dementia. And since the number of Alzheimer’s patients in the United States is expected to triple over the next 40 years, improved treatments and prevention are more crucial than ever, says Zaldy Tan, MD, MPH, director of the Bernard and Maxine Platzer Lynn Family Memory and Healthy Aging Program, and medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders at Cedars-Sinai. Here, Tan, a leading memory and aging specialist, shares his vision for the future of dementia care.
What are the most significant ways we can improve care for dementia patients?
Managing dementia is extremely challenging, especially in primary care. Patients may miss appointments and have difficulty understanding medication instructions. They can develop behavioral issues, and their caregivers become stressed. In our Bernard and Maxine Platzer Lynn Family Memory and Healthy Aging Program, we are building a truly multidisciplinary team tailored to the complex needs of patients with dementia. It’s an innovative approach. Our team—a memory specialist, pharmacist, neuropsychologist, social worker, genetic counselor and nurse practitioner—gets to know each patient and their needs. It’s crucial to continually evaluate dementia
18 | DISCOVERIESMAGAZINE.ORG
patients from several perspectives, addressing their cognitive, behavioral and social challenges. This helps prevent unnecessary hospitalizations or trips to the emergency department, since people with dementia don’t do well in the hospital. We develop personalized, comprehensive care plans for each patient’s family or caregivers, as well as their primary care doctor. It’s also crucial for us to address caregiver depression and burnout, which make it more likely that a patient will end up in the emergency department. We offer caregivers education, support and referrals to communitybased services. Why is your work with caregivers so important? It is
challenging for a family mem-
ber to be thrust into the role of caregiver for a loved one with dementia whose needs may exceed most people’s knowledge and skills. In 2019, I published a study that found that attending a one-day intensive boot camp made caregivers more knowledgeable and more confident in their skills. Busy caregivers have limited time to devote to education and training; we found that even a one-day investment is enough to make a lasting difference. What more do we need to learn about dementia risk and prevention? There are
segments of our diverse Los Angeles community whose dementia risk and outcomes remain largely unexplored. That’s why we are recruiting Asian American and Pacific
Islander (AAPI) and LGBTQ+ individuals at increased family risk for dementia for a study on brain aging. We will be following them for life to help discover why some people develop dementia and some do not. Not much is known about the AAPI population’s risk for dementia—the little data we have seems to show that Asian people have a lower dementia risk. If that’s confirmed, perhaps there are resilience factors we could identify that can help reduce everyone’s risk of developing memory problems. It is also possible that the low incidence may reflect underreporting because there are cultural barriers to obtaining a diagnosis. If the data supports this, we can develop ways to address those barriers for AAPI populations and for other minorities. Though LGBTQ+ patients are diverse in terms of race and culture, one commonality may be exposure to adverse social determinants of health: discrimination, lack of access to good healthcare and social isolation. Many older LGBTQ+ adults live alone without the benefit of traditional family structure and support. We don’t know whether these negative social determinants of health translate to an increased risk for developing dementia. What are the most exciting advances in dementia research? The recent Food
and Drug Administration
ZALDY TAN, MD, MPH Carmen and Louis Warschaw Chair in Neurology; Medical Director, Jona Goldrich Center for Alzheimer’s and Memory Disorders; Director, Bernard and Maxine Platzer Lynn Family Memory and Healthy Aging Program Path to L.A. Tan trained at Brown University and Harvard Medical School and studied at Harvard Business School and School of Public Health. He moved to Los Angeles 10 years ago to be closer to his family. In Another Life If he wasn’t a doctor, Tan may have gone Hollywood. He studied screenwriting at the UCLA School of Theater, Film and Television. Valuable Advice “Being in the field of memory, I have a great appreciation for forming good memories when you’re younger,” he says. “Material things lose value over time, but memories only become more valuable. In the end, the experiences we’ve had and the people we’ve met make us richer and will always be with us.”
What inspired you to special-
AL CUIZON
Dr. Zaldy Tan is leading a study into who is at risk for developing dementia, and why.
approval of disease-modifying therapies, including aducanumab, is a start, though it’s uncertain whether these treatments will be effective for slowing down cognitive and functional decline. We need more evidence about these medications’ effectiveness, safety and accessibility. We are close to having a
blood test that can tell clinicians, with a high degree of reliability, whether a patient is developing Alzheimer’s, even before they have symptoms. And I am very interested in personalized health, since each person has a unique set of risk and preventive factors for Alzheimer’s. In the future, I envision that we
will treat patients on the path to memory loss with oral therapy or intravenous infusions, depending on what type of dementia they are most likely to develop. Monoclonal antibodies that clear the brain of the abnormal amyloid or tau proteins also hold promise as future Alzheimer’s disease treatments.
ize in memory disorders? My mom is the third of five sisters, and her two older sisters, my aunts, both had dementia. I’ve seen firsthand how it robs people of memories and compromises relationships they treasure, so I have an interest in finding a way to reduce the risk of dementia and achieve the best care possible for people who do have it. As we develop more therapies, a lot of good can be done to help people through this journey.
SUMMER 2022 | DISCOVERIES |
19
Learn
Lessons From a Pandemic By VICTORIA PELHAM When COVID-19 brought the world to a standstill, healthcare workers dug into their roles and networked to pioneer lasting innovations. Through the creation of a CedarsSinai COVID-19 Research Task Force and partnerships with other health institutions, physicians and researchers collaborated to understand the pandemic, even as information—and the virus itself— rapidly evolved. Investigators across specialties initiated more than 100 studies focused on COVID-19, while physicians and supply-chain teams raced to meet the crushing demand. Such teamwork was at the root of a fundamental transformation in medicine. Lessons learned laid the foundation for how effectively we will respond to the next pandemic, which could hit sooner than feared: Global health-risk modeling estimates there is about a 50% chance that a new viral or bacterial outbreak on the same scale as the current pandemic will occur in the next 25 years. “Everyone was forced to invest so much effort, time and material into this pandemic that we’ve learned a lot that can be useful in future pandemics,” says Peter Chen, MD, director of Pulmonology and Critical Care Medicine and the Medallion Chair in Molecular Medicine at Cedars-Sinai. Treatments and Vaccines Take a Quantum Leap
Less than a year after the identification of SARS-CoV-2, the virus that causes COVID-19, groundbreaking studies led to
20 | DISCOVERIESMAGAZINE.ORG
Food and Drug Administration approval of remdesivir, monoclonal antibodies and oral antivirals to treat the disease. Multisite clinical trials taught scientists much about treating viral infections. Through collective study, we learned that drugs originally developed for other illnesses, including Ebola, could be recalibrated to fight viruses in the same family as SARS-CoV-2, such as SARS and MERS. “It shows what our machinery can do when we really put everything into it,” Chen says. Pandemic research also led to the creation of the first-ever coronavirus vaccines. Two of the approved vaccines trigger an immune response by using messenger RNA (mRNA) to teach cells how to produce harmless spike proteins that mimic those that open cells to SARS-CoV-2. Researchers have been studying mRNA vaccines for decades, but COVID-19 vaccines are the first to be introduced to the public. “Now that we have the method down and mechanisms to improve it, we can very quickly tweak the vaccine to work against the next virus,” Chen says. Infectious Disease Can Affect Genders Differently
Susan Cheng, MD, MPH, MMSc, director of Public Health Research and the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science, leads Cedars-Sinai studies on the impact of COVID-19 on diverse populations. Having established the multihospital Coronavirus Risk Associations and Longitudinal
Evaluation (CORALE) study network, her teams discovered gender differences so profound they could not be “wiped away with the strongest eraser,” Cheng says. Even after adjusting for other risk factors, the researchers found that men are more vulnerable to COVID-19 than women and exhibit a more exaggerated immune-inflammatory response. “This is the tip of many icebergs in terms of helping us to better understand intrinsic biological sex differences in health and disease,” Cheng says. “We are going to have to keep thinking about how some diseases present very differently in males versus females.” Outbreaks Take Advantage of Existing Structural Inequities
Cheng also examined the toll of COVID-19 on minorities, who have borne the brunt of infections, hospitalizations and deaths during the pandemic. Her team found that Black and Latino healthcare workers were more likely to have previously had a SARSCoV-2 infection than their counterparts and were more frequently exposed in the community, not at work. The role of housing is underestimated, Cheng says, because many vulnerable populations are more likely to live in multifamily units, which creates settings for the virus to spread more rapidly. High-Quality Communication Is Key
Ever-shifting pandemic guidelines caused some public confusion and distrust. Explaining the difference between highquality and low-quality data was a crucial challenge for public health officials, says Jonathan Grein, MD, director of Hospital Epidemiology at Cedars-Sinai. Medical professionals should clearly communicate what emerging, oftenconflicting studies mean and explain study methodologies and limitations, Grein says. For example, early findings on the
KATHLEEN FU
protective value of masks relied on specific laboratory circumstances that were challenging to apply to the real world. Later evidence building the case for masks was derived from larger studies that showed their effectiveness in communities and settings with high SARS-CoV-2 spread and among people with asymptomatic or presymptomatic infections. Strengthening public confidence in science could ensure better adherence to vital safety recommendations in a future pandemic.
Genetic Research Into New Bugs Should Be a Priority
Conducting research during a pandemic felt like “building the boat while sailing,” 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. Arditi’s exploration of a COVID-19linked pediatric inflammatory syndrome,
similar to toxic shock, uncovered viral molecules that induce the condition. He discovered biomarkers that reveal genetic predispositions and predict severity of the disease. Understanding who might develop serious complications could enable providers to make better care decisions. Arditi hopes that elucidating biomarkers produced by COVID-19 patients will encourage greater investment toward understanding emerging pathogens— before the next pandemic strikes.
SUMMER 2022 | DISCOVERIES |
21
THE
NEW
LUNG
CANCER
LAND-
SCAPE
Public health efforts and scientific advances have led to a significant drop in lung cancer deaths, but researchers are still searching for cures for the No. 1 cancer scourge.
By NICOLE LEVINE
Illustration by JOHN W. TOMAC Portraits by MISHA GRAVENOR
22
SUMMER 2022 | DISCOVERIES |
23
KAREN RECKAMP, MD, WAS STUDYING THE IMMUNE SYSTEM DURING HER SPECIALTY FELLOWSHIP, TRAINING HER SIGHTS ON A CAREER AS AN ONCOLOGIST FOCUSED ON STEM CELL TRANSPLANTATION, WHEN A NEW DISCOVERY SHOOK THE CANCER WORLD. In 2004, researchers identified a specific mutation in some lung cancer cells, a breakthrough that changed the understanding of lung cancer biology. Rather than being divided into two simple categories—small cell lung cancer and non-small cell lung cancer—lung cancer became a group of diseases defined by their genetic underpinnings. “Before this, you treated patients with various chemotherapies depending on whether they had small cell or non-small cell lung cancer—no other factor mattered, and the outcomes were not very good,” says Reckamp, associate director of Clinical Research for Cedars-Sinai Cancer and director of Medical Oncology in the Department of Medicine. “Suddenly, lung cancer became a completely different disease. It was exciting, and I was all in.” This breathtaking shift in lung cancer medicine ushered in the possibility of treatments that home in on tumor-cell DNA, and the cascading effects of this change continue to be felt. For decades, the statistics on lung cancer told the same sobering story: It’s the leading cause of cancer death in the United States and the world, causing more deaths than breast, colon and prostate cancers combined. Today, death rates from lung cancer are in an accelerated decline due to progress across the spectrum of cancer care. Outcomes are better. People who are diagnosed are living longer with enhanced quality of life. The decline is significant enough that it cannot be explained by the drop in smoking rates alone. A sophisticated understanding of genetics, an expanding arsenal of personalized treatment options, the availability of lung cancer screening and public health efforts have all combined to transform the landscape for those who treat and live with this formidable disease. However, only a very small fraction of eligible high-risk patients undergo screening. Access to treatment and care can be challenging for many. And, while treatments are good, few
24 | DISCOVERIESMAGAZINE.ORG
patients are declared cured: Living longer with lung cancer is different from being free of the disease. While a more sophisticated understanding of lung cancer biology and groundbreaking treatments offer reasons to be hopeful, stigma and fear attached to the disease also persist—and feed into the gulf between the ability to screen for the disease and catch it early and
the number of people willing to be screened. Cedars-Sinai investigators are working to bridge that diagnosis gap while advancing treatments for the cancer that still kills the most people worldwide. Not Just a Smoker’s Disease
The first time Di’Ann Smith, 74, ever saw a Los Angeles Rams game at SoFi Stadium, she was there to do more than cheer for her home team. She was a guest of honor promoting lung cancer awareness as she stood by Reckamp, her longtime oncologist. Smith was especially interested in sharing one fact: Anyone with lungs can get lung cancer. She would know. “Back when I quit smoking in 1992,
Dr. Karen Reckamp works to improve lung cancer care from diagnosis to treatment.
everyone said that after five years your lungs go back to being pink and healthy and you’re free,” she says. “That wasn’t the case for me. My lung cancer showed up 15 years after I quit.” According to the American Cancer Society, within 10 years of quitting smoking, a person’s lung cancer risk drops to half that of those who still smoke. Despite the public’s perception that the disease only affects smokers, up to 20% of lung cancers nationwide occur in people who have never smoked. Environmental or genetic factors may play a role. “We’re still trying to understand all risk factors associated with lung cancer,” Reckamp says. “In many cases, we cannot be entirely sure why someone develops the disease— especially as it occurs in people who never smoked.” Homing In On Targeted Therapies
The success of targeted therapies is one of the most powerful driving forces behind the decline in lung cancers. Every cancer cell has its own genetic fingerprint and, like all cells, cancer cells have different systems for communicating and replicating. While a cancer might be commonly called lung cancer or breast cancer, they are groups of diseases with considerable genetic distinctions. Traditional chemotherapies work by attacking any cells that are dividing rapidly—whether they’re healthy or malignant. Targeted therapies work differently, disrupting cancer cells by selectively interfering with proteins on those cells that carry specific genetic alterations. While chemotherapy kills the cells it touches, targeted therapies typically prevent new cells from growing. The targets vary from cancer to cancer, and not every cancer has a mutation that
matches one of the therapies currently available. The Food and Drug Administration (FDA) has approved a multitude of drugs for eight genetic targets in lung cancer. Smith’s lung cancer was initially treated in North Carolina, where she had surgery to remove the upper right lobe of her lung, followed by two rounds of chemotherapy. When she moved to California, she started seeing Reckamp. New traces of cancer in her lungs are now being treated with targeted therapy in the form of a daily pill. The treatment is working well enough that the frequency of her visits has dropped from four times a year to three. “I’m so grateful there’s a targeted therapy that works for me,” Smith says. “My mind is at ease knowing that I’m taking a medication that is taking care of whatever is happening in my lungs.” The cancer mutation that changed the trajectory of lung cancer occurs in EGFR, which stands for “epidermal growth factor receptor.” EGFR is a protein found in healthy cells that stimulates cell growth. Cancer cells that have a mutation in this protein send faulty instructions to healthy cells, causing them to grow too much and spawn new cancer cells. The discovery of this mutation led to the development of drugs that block EGFR from sparking cell overgrowth. As many as 15% of lung cancers in the United States are positive for EGFR mutations, and they are more common on the West Coast due to its higher concentration of nonsmokers and people of Asian descent— two groups more likely to develop EGFR-positive lung cancers. Thanks to targeted therapies, outcomes are improving for these patients, even if their lung cancer has spread.
Overcoming Resistance Targeted therapies are major contributors to the diminished impact of lung cancer. However, over time, the disease tends to find a way around these treatments. Often, the response in the research world is to go back to the lab to find a medication that bypasses the new mutation. “There will always be more mutations, and we can keep trying to find more and more drugs that work against them, but that’s a race you would never win,” says Neil Bhowmick, PhD, director of the Cancer Biology Program in the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai. He knows the path from “managed” cancers to “cured” cancers has to traverse the cellular resistance problem. So Bhowmick teamed up with Reckamp to look for a mechanism to explain how cancer cells find a way to overcome EGFRtargeted therapies. They began with a drug called osimertinib, which has a good track record for slowing down cancer in patients whose tumors test positive for EGFR. Bhowmick and his colleagues study the role of a favored communication pathway of many cancer cells called the bone morphogenetic protein, or BMP. This protein sends information to cancer cells and surrounding healthy cells. The research team discovered a potentially important link between the EGFR-targeted drug osimertinib and BMP that could help explain the resistance that develops: While the drug successfully fights the cancer on other fronts, it seems to promote BMP-based communication as a means of survival and expansion. Manish Thiruvalluvan, PhD, a postdoctoral fellow on Bhowmick’s team, discovered that, over time, cancer cells escaped osimertinib by going into a state called “cancer dormancy,” meaning they’re essentially asleep. This adaptation slows their growth but also makes the cells invisible to the immune system and to the targeted cancer drugs seeking them out. BMP acts like a lifeline for these sleeping cells, keeping them in touch with both malignant and healthy cells in the body while evading medications. The team found a way to wake them up using a drug that thwarts the BMP pathway. In preclinical cell and mouse models where a combinationtherapy strategy was used to block BMP communication, the cancer again became vulnerable to osimertinib. Reckamp will soon lead a Phase I trial testing the safety of the combination—the drug that wakes up the cells by blocking the BMP pathway and the EGFR-fighting osimertinib. “Hitting cancer dormancy could be an effective strategy to extend the efficacy of targeted therapies,” Bhowmick says. “It could get us away from the never-ending whack-a-mole story of going after the next new mutation.” To continue the metaphor, the first drug blocks other avenues for the cancer, or “mole,” so it can only pop up from one hole. The “hammer”—the second drug—thus knows exactly where to hit.
SUMMER 2022 | DISCOVERIES |
25
“We know we’re actually improving survival for patients with advanced disease,” Reckamp says. “They’re living longer because of the treatments we have available now, and that’s largely due to treating EGFR mutations.” An Underused Tool
Even as treatments for lung cancer advance at an extraordinary rate and screening is at last available and covered by insurance, the number of people being screened is lagging, especially in California. One reason lung cancer has been such a deadly disease is that it is often in a late stage by the time symptoms arise. In 2015, Medicare started covering screening with a low-dose CT scan for those at highest risk, a measure that could save as many as 12,000 lives annually. According to the American Lung Association, only 5.7% of those eligible were screened for lung cancer in 2021. Experts project that as many as 20% of lung cancer deaths could be prevented through early detection. Lack of access to healthcare and limited awareness among patients and providers contribute to the low screening rates. “Screening is an area where we have enormous potential to save lives—but we’re not there yet,” says radiologist Christopher Lee, MD, who is developing Cedars-Sinai’s lung cancer screening program with Sara Ghandehari, MD, director of Pulmonary Rehabilitation in the Women’s Guild Lung Institute at Cedars-Sinai. “California is dead last in the country—only screening 1% of those at high risk—so we may not be seeing as much of a decline in lung cancer deaths as we could here in our state.” In building the new program, Lee, Ghandehari and their colleagues examined obstacles to screening. For starters, the guidelines, which were updated in 2021 to include more people, are complicated. Screening is recommended for those ages 50 to 80 who are in fairly good health and either smoke or have quit in the last 15 years. They also must have a smoking history of at least 20 pack-years. (A pack-year is the number of cigarette packs smoked per day multiplied by the number of years the person smoked. Someone who smoked a pack a day for 20 years would qualify, as would someone who smoked two packs daily for 10 years.) Another difficulty is that people must have access to a primary care physician to discuss their smoking history, assess their eligibility and receive appropriate education. “Many people—especially in California—got the message about smoking and quit,” Lee says. “Once you quit, the topics of smoking and lung cancer risk almost never come up with your doctor, despite the fact that you’re
26 | DISCOVERIESMAGAZINE.ORG
still at high risk for many years after you quit.” Previously, Lee worked with Cedars-Sinai’s Cancer Research Center for Health Equity on a twoyear pilot study the center conducted with Watts Healthcare Corporation in South Los Angeles that successfully screened more than 500 patients. The program used a combination of strategies, including providing transportation to screening appointments, training community navigators, and working with churches and community organizations to promote screening. The successful community navigator approach is now being tested in other neighborhoods. Ghandehari and Lee are designing a program based on a strong multidisciplinary team to support patients and coordinate their care through every step of the process. A key aspect of the program, Ghande-
hari explains, is the nurse-navigator, who can identify which patients qualify for screening and provide education and smoking-cessation counseling when needed. In addition, the nurse-navigator also discusses risks and benefits of screening. “We want to give patients robust support through the screening process and also through follow-ups when the results return,” Ghandehari says. “We want to be strong partners for patients and their doctors.” Resolving Disparities
California lags behind the rest of the nation in providing treatment to patients diagnosed with lung cancer. According to the American Lung Association, 27% of people diagnosed with lung cancer in California are never treated at all: The state ranks 46th out of 49 ranked states for treatment. Nationally, 21% of patients are untreated.
All in a Day’s Work The average time between a lung cancer diagnosis and surgery to remove the tumor is 52 days. Harmik J. Soukiasian, MD, director of the Division of Thoracic Surgery at Cedars-Sinai, is aiming to dramatically reduce that wait time. In fact, for some patients, he is cutting it down to a single day for biopsy, diagnosis, surgery and treatment—with some robotic assistance. “We now have technology that allows us to meet and treat the patient all in one day,” says Soukiasian, who is the Tawil Family Chair in Thoracic Surgery. For patients who are appropriate candidates for the procedure, Soukiasian first performs a biopsy with a robotic platform that creates a 3D map of the patient’s lung. The surgical team uses the map and a camera to precisely navigate the robot to the suspicious mass and obtain a sample. The tissue sample is delivered to a pathologist who, in 15 minutes, can determine whether the mass is cancerous. If the diagnosis is cancer and it’s confined to the lung, the patient undergoes a second robotic procedure. The surgeon operates from a console, directing the robot using magnified 3D images and video to precisely remove the mass, lymph nodes and, if necessary, a lobe of the lung through several small incisions. The combined procedures can be completed in about three hours. “We can shorten the time that patients and their loved ones struggle with the unknown and get them clear of their disease faster,” Soukiasian says.
tests that make targeted therapies possible, and that is especially true among minority groups, Reckamp says. She hopes that efforts aimed at improving outcomes for all will help address the gap. “We will test every person who comes through the door to determine the best treatment based on their DNA and the genetics of their cancer,” Reckamp says. “It’s simply a best practice that will get every patient from their diagnosis to the right treatments as quickly as possible.” Next Frontiers
Di’Ann Smith is the beneficiary of targeted therapy for her lung cancer.
The numbers are worse for minority populations, especially Black patients. They’re less likely to be diagnosed at an early stage— 21% compared to 26% among white patients. They’re also more likely to have their cancer go untreated: 30% of Black Californians with lung cancer receive no treatment at all. They’re the least likely of any ethnic group to undergo surgery for lung cancer, tied with the national rate of 17%, but lower than the 22% rate among white lung cancer patients in the Golden State. “We know lung cancer disproportionately affects minority communities, who are also less likely to have access to care,” says Zul Surani,
MPH, director of Community Outreach, Engagement and Operations at the Cancer Research Center for Health Equity at Cedars-Sinai. “We know we have the treatments and technology to improve lung cancer outcomes. Now, we have to go to those high-risk communities and help them get the screenings and treatments they need.” As a lung cancer survivor, Smith hopes to see disparities experienced by her community addressed so that everyone has access to the care that has kept her alive for more than 15 years. “Dr. Reckamp was the first doctor to ever talk to me about targeted therapies,” she says. Not enough patients undergo the
A broadening understanding of lung cancer biology has opened doors to treating the disease, Reckamp says. Immunotherapy is a novel treatment that harnesses a patient’s own immune system to identify and attack cancer cells. These therapies have changed the way physicians treat advanced lung cancer since 2015, but in 2021 the FDA approved immunotherapy in early-stage lung cancer following surgical removal of part of the lung. This is especially promising for patients whose cancer will not respond to targeted therapy. With chemotherapy, ever-advancing surgical techniques, precision targeted therapies and immunotherapy, doctors have a more robust toolkit than ever before to address the deadliest of cancers. The numbers reflect the progress. The five-year survival rate for lung cancer patients has climbed from 14.5% to 23.7% nationally, according to the American Lung Association’s most recent report. It’s a dramatic statistic that illustrates the lifesaving power of these scientific advances. Those numbers also reflect the urgency felt by the lung cancer community—patients, their loved ones, and healthcare providers and scientists who are determined to find better solutions. “Despite all these amazing advances and our deeper understanding of the biology, despite the fact that we’re benefiting patients and they’re living longer lives, we’re still not curing enough people,” Reckamp says. “Until we have better cures, we still have a long way to go.”
SUMMER 2022 | DISCOVERIES |
27
DI SCOVERIES
BY
I L LUST RAT I O N BY
PO RT RA I T BY
Dramatic advances in the field of minimally invasive heart valve replacement are extending and improving life for millions of previously untreatable patients. Cedars-Sinai physicians are seeking the next frontier.
Cassie Tomlin
Arthur E. Giron
Mark Leibowitz
KEEP ON
TICKING Jane Booth was aghast when her cardiologist told her she needed heart surgery.
Booth, a yoga and tennis enthusiast who walks 5 miles a day, had nevertheless developed severe aortic valve stenosis, the result of a congenital heart defect identified by chance years ago. Over time, the faulty structure of her heart’s major valve caused it to narrow, putting her at risk for heart failure. But the otherwise healthy 65-year-old felt fine and couldn’t fathom undergoing open-heart surgery for a condition that seemed to have no impact on her active life. • Late at night, Booth would lay awake fearing her own heartbeat. On brisk walks, she’d get short of breath and wonder, “Is this it? Is this what the doctors were talking about?” • Staggering advances over the last 10 years have revolutionized the treatment of heart valve disease, a diagnosis shared by about 5 million new PG
28
patients annually. A decade ago, doctors treated valves with medication or open-heart surgery—or not at all. Today, innovative minimally invasive repair or replacement techniques performed by interventional cardiologists save, extend and improve the lives of countless patients previously considered too old or frail for surgery. And the paradigm-shifting procedures continue to evolve: The Smidt Heart Institute at CedarsSinai is a world leader in transcatheter aortic valve replacement (TAVR) for the oldest and sickest patients and also for healthier patients like Booth. The widespread adoption of this minimally invasive technique and its game-changing growth to a wider population is largely thanks to the tireless, methodical research of Booth’s physician Raj Makkar, MD— and a pioneering, collaborative careteam approach. Cedars-Sinai physicians have performed more TAVR procedures than any other U.S. center and continue to make leading-edge advances on catheter-based fixes for all four heart valves. “With these procedures, we make a real impact,” says Makkar, associate director of the Smidt Heart Institute and the Stephen R. Corday, MD, Chair in Interventional Cardiology. “Our mission is not just to follow the lead but to constantly refine our work to open new gateways.” Disruptive Technology
Heart valves often get tight or leaky with age, which causes fatigue and trouble breathing and, if left untreated, can be fatal within two years—a prognosis worse than many cancers, Makkar notes. The old standard for repair and replacement was open-heart surgery: an incision down the breastbone and connection to a heart-lung machine while a
30 | DISCOVERIESMAGAZINE.ORG
“ O UR MISSION IS NOT JUST TO FOLLOW THE LEAD BUT TO CONSTANTLY REFINE OUR WORK TO OPEN NEW GATEWAYS.” Raj Makkar, MD
physician removes the diseased valve and replaces it with an artificial one made of metal or human or animal tissue. Afterward, patients would recuperate in the intensive care unit and require at least five days of hospitalized recovery. The rise of TAVR challenges the old concept of heart surgery for valvular issues. It can restore aortic valve function to normal with fewer complications, less pain and shorter recovery time than open-heart surgery, all because of the nimble elegance of the procedure: A catheter is threaded into an artery in a patient’s leg and acts as a “railway” to deliver the replacement valve. Guided by X-ray, an interventional cardiologist—not a surgeon—positions the new valve within the old one and, immediately, blood flow improves. The wires are removed, and patients typically stay overnight before recovering at home. Makkar performed Cedars-Sinai’s first TAVR in 2007, following an introduction at a conference to French interventional cardiologist Alain Cribier, MD—a former fellow at Cedars-Sinai who performed the world’s first TAVR in 2002. The encounter clarified the trajectory of Makkar’s career: He immediately recognized TAVR as the next wave in his field. He led enrollment in landmark multicenter trials that directly contributed to the Food and Drug Administration’s approval of TAVR, first for patients over 65 who are inoperable or at high risk for surgical complications, and later for low-risk patients. In 2020, Makkar published the results of a five-year study in the New England Journal of Medicine demonstrating that patients who underwent TAVR did just as well over the long term as those who underwent traditional surgery. “The early days were very exciting and slightly nervewracking because the first-generation catheter was much bigger, and patients were much older with many underlying conditions,” Makkar says. “Even in these patients who were very sick and very old, we were able to do it safely.” As valve design evolved, Makkar continued to push the envelope. Early studies of TAVR excluded patients with bicuspid aortic valve, the condition Booth was born with. A bicuspid aortic valve has only two “leaflets,” the flaps that act as the valve’s doors, instead of the usual three. Such valves degenerate faster than normal aortic valves and were initially thought to be too risky for TAVR. But in 2021, Makkar published an analysis in the Journal of the American Medical Association finding nationwide outcomes of TAVR for low-risk patients with bicuspid aortic valve ste-
nosis had the same risk of death or stroke at 30 days and at one year as those with normal aortic valves. Expanded Benefit
For Booth, a routine electrocardiogram nearly 10 years ago revealed her faulty bicuspid aortic valve, and she began to see a cardiologist twice a year for monitoring. In 2019, the valve had deteriorated enough that her aortic stenosis was getting severe, and she was introduced to a surgeon. He suggested surgical valve replacement, which would have had Booth recovering for 60 days. She’d only ever been hospitalized to deliver her children and was wary of such an intensive procedure. Inspired by her late husband, Skooter, who had been meticulous about his own health, she wanted a second opinion, and a family member suggested she contact Makkar. She met the qualifications for TAVR, and Makkar’s office kept in close contact with her as they waited for approval from Booth’s insurance. “Makkar’s team was so attentive, patient and always available,” Booth says. “It was comforting to know they were backing me.” Last October, Makkar performed the procedure, alongside a cardiothoracic surgeon, in case of emergency, and flanked by fellows (his trainees have gone on to lead programs at Yale and Stanford). Booth was home the next afternoon. Three weeks later, she was back at her regular tennis clinic. The next month, Booth— “Tutu” to her six grandkids—hosted Thanksgiving for her entire family. “Dr. Makkar’s work has revolutionized the way we take care of patients,” says Christine Albert, MD,
interventional cardiologists work closely with highly specialized cardiac surgeons, electrophysiologists, congenital heart physicians, anesthesiologists, imaging specialists and palliative care physicians to determine their optimal approach, which has evolved in tandem with TAVR. Expanded options have fostered more collaboration among specialists, who assess risks and benefits from varying perspectives, ensuring a personalized approach and wraparound support for each patient. “Rather than being siloed as cardiologists or cardiac surgeons, it’s routine for us to evaluate patients as a heart team,” Makkar says. “We discuss complex cases, and together we come up with a unified management plan. In a way, this new technology also led to the evolution of how we actually care for patients.” Next Frontier
Jane Booth was able to avoid open-heart surgery thanks to a technique pioneered at Cedars-Sinai.
MPH, founding chair of the Department of Cardiology in the Smidt Heart Institute and the Lee and Harold Kapelovitz Distinguished Chair in Cardiology. “Leaders from all over the world joined forces to study this technology, which has been incredibly important in changing the way we practice medicine.”
Teamwork Revolutionized
Smidt Heart Institute physicians have performed more than 5,900 TAVR procedures on patients as young as 38 and as old as 100. But a catheter-based approach isn’t always best. For each patient, Makkar and other
Today, Booth marvels at the “miracle” of her valve replacement and is grateful she can recognize a change in her body after her easy and complete recovery. “I was in denial until I woke up from my procedure, took in the deepest breath I’d ever taken and exhaled so long it went on for miles,” Booth says. “I was so glad that I could feel a difference.” Makkar continues to study how to improve minimally invasive procedures. He is principal investigator on 19 active clinical trials, including studies of novel catheter-based replacements for mitral, tricuspid and pulmonary valves. “Ten years ago, it was inconceivable that we would be replacing mitral or tricuspid valves,” Makkar says. “We now have the tools, and early indications are that it is safe and feasible. This is where the field is moving.”
SUMMER 2022 | DISCOVERIES |
31
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
Education
Full-Circle Healing
A doctor’s education in trauma care began in college
AL CUIZON
By AMY PATUREL, MS, MPH
When Nicole Fierro, MD, was a little girl, she set her sights on becoming a doctor. Her parents were not in the medical field. Her mother worked for a wireproduction plant in South El Monte and her father was in construction. In fact, no one she knew had been to college. As a Latina who grew up in the San Gabriel Valley with four brothers, Fierro was exposed to the effects of gang violence and trauma from an early age. She also recognized the health disparities within her community. “I knew that minorities were at an increased risk of experiencing gun violence, trauma and assault,” says Fierro, now 30. And she knew she wanted to be part of the solution. The doorway to her future career opened during Fierro’s sophomore year at UCLA when she learned about CedarsSinai’s Trauma Research Program (TRP) through a student listserv. Students in TRP attend weekly lectures, present research on relevant surgical topics and get on-the-ground training in the medical field. Fierro applied, and the TRP team selected her to join their ranks. As a member of TRP, Fierro gained a front-row seat to clinical research at one of the top Level I trauma centers in the (continued on page 35) country.
Dr. Nicole Fierro trained in CedarsSinai’s Trauma Research Program and now mentors the next generation of students.
33
Faculty News
Medical residents Akbarshakh Akhmerov, MD, and Arjan Gower, MD, won the 2021 CedarsSinai Rubenstein Award for Excellence in Resident Research based on their studies of inflammation and pancreatic cancer, respectively. The annual award, which carries a $3,000 cash prize for each winner, fosters clinical and translational research, leads to enriched knowledge, and encourages career development of our residents as investigators. Harriet U. Aronow, PhD, professor of Medicine and Biomedical Sciences, has been named an honorary fellow of the American Academy of Nursing. With a 40-year career in applied health services and evaluation research, she works to develop nursing-sensitive performance indicators and a benchmark data registry for ambulatory care nursing. Peter Chen, MD, director of the Division of Pulmonary and Critical Care Medicine, has been named the Medallion Chair in Molecular Medicine. A leading authority in the field of lung injury and repair, Chen has made seminal discoveries in understanding lung-repair mechanisms and has applied these findings to patient care at CedarsSinai since 2013. The 2021 Cedars-Sinai Clinical Fellows Awards for Excellence in Research were presented to Smidt Heart Institute fellows Jae Hyung Cho,
MD, PhD, for his work on the role of inflammation in heart failure with preserved ejection fraction, and Lily K. Stern, MD, for her study of the impact of the 2018 revision to the United Network for Organ Sharing’s donor heart allocation system. Sumeet S. Chugh, MD, the Pauline and Harold Price Chair in Cardiac Electrophysiology Research, medical director of the Heart Rhythm Center and director of the Center for Cardiac Arrest Prevention, has been elected president of the Cardiac Electrophysiology Society. John P. Chute, MD, has been named the Linda Ostrowski Chair in Hematology/Oncology in honor of Barry Rosenbloom, MD. He is director of Hematology and Cellular Therapy in the Department of Medicine at Cedars-Sinai Cancer, director of the Center for Myelodysplastic Diseases Research, and associate director of the Board of Governors Regenerative Medicine Institute. 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 inducted into the American Society for Clinical Investigation. The society supports the scientific efforts, educational needs and clinical aspirations of physicianscientists to improve the health of all people.
34 | DISCOVERIESMAGAZINE.ORG
David Gibb, MD, PhD, assistant professor of Pathology and Laboratory Medicine in the Division of Transfusion Medicine, received the 2021 National Blood Foundation Award for Innovative Research. Anita Girard, DNP, RN, has been appointed chief nursing officer for Cedars-Sinai Medical Center and will manage nursing operations across the center. She joined Cedars-Sinai in April 2020 as vice president of nursing; this new position is an evolution of her previous role. Irene Kim, MD, director of the Comprehensive Transplant Center and surgical director of Kidney Transplantation, has received the Outstanding Women in Healthcare Award from the American Liver Foundation. Kim was also elected to the council of the American Society of Transplant Surgeons and to the board of the United Network for Organ Sharing.
Services and the David and Meredith Kaplan Distinguished Chair in Children’s Health. Klein previously served as chief of the Division of Medical Genetics, chair of the Division of Craniofacial Anomalies and director of the Institute for Human Genetics at the University of California, San Francisco. An internationally recognized innovator in pediatrics and genetics, Klein has received the Director’s New Innovator and Sustaining Outstanding Achievement in Research awards from the National Institutes of Health as well as the E. Mead Johnson Award from the Society for Pediatric Research. He has been elected to the National Academy of Medicine, American Society for Clinical Investigation and Association of American Physicians and is a fellow of the American Association for the Advancement of Science.
Jayoung Kim, PhD, professor of Surgery and Biomedical Sciences, has received the silver President’s Volunteer Service Award for her contributions and dedication to promoting health equity, diversity and inclusion. Kim was awarded a certificate of achievement in September from President Joe Biden.
Errol P. Lobo, MD, PhD, has joined Cedars-Sinai as chair of the Department of Anesthesiology. A respected academic leader, anesthesiologist and diversity advocate, he was previously vice president of Perioperative Services, president of the medical staff, and professor of Clinical Anesthesia and Perioperative Care at the University of California, San Francisco School of Medicine.
Ophir Klein, MD, PhD, has been appointed inaugural executive director of Cedars-Sinai Guerin Children’s, vice dean for Children’s
Shelly C. Lu, MD, director of the Karsh Division of Gastroenterology and Hepatology in the Department of Medicine and the Women’s Guild
Chair in Gastroenterology, received the 2021 Cedars-Sinai Prize for Research in Scientific Medicine (PRISM), an annual award that recognizes a scientific breakthrough or critical medical insight made within the past five years by a Cedars-Sinai faculty member. Lu was honored for her translational studies revealing novel molecular mechanisms contributing to liver disease and for innovative approaches to therapy for fatty liver disease and cancer. David Marshall, JD, DNP, RN, has been named the James R. Klinenberg, MD, and Lynn Klinenberg Linkin Chair in Nursing in honor of Linda Burnes Bolton. Marshall, who has more than three decades of healthcare experience— from improving nursingleadership proficiency and fostering innovation to championing compassionate care—is senior vice president, chief nursing executive and chair of the Department of Nursing at CedarsSinai. Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs, dean of the medical faculty, and the Helene A. and Philip E. Hixon Distinguished Chair in Investigative Medicine, has been selected as the inaugural recipient of the Transatlantic Alliance Award. The prestigious joint award of the Endocrine Society and European Society of Endocrinology recognizes an international leader who has
made significant advancements in endocrinology research through work and collaboration in both the United States and Europe. Russell MetcalfeSmith, MSc, director of the Women’s Guild Simulation Center for Advanced Clinical Skills, has been named a fellow of the Society for Simulation in Healthcare Academy and was certified as an advanced healthcare simulation educator and simulation operations specialist, becoming the first person in the world to achieve all three designations. Sukhmani Padda, MD, has been named director of Thoracic Medical Oncology at Cedars-Sinai Cancer. Her research focuses on therapies for thoracic cancers, improving treatment for genomic subsets of lung cancer and rare thoracic tumors. She also studies tumor biomarkers to determine the best treatments for patients. Previously, she was an assistant professor of Medicine at Stanford University. Zaldy Tan, MD, MPH, has been named the Carmen and Louis Warschaw Chair in Neurology. A leading memory and geriatric medicine specialist and dementia investigator, Tan is medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders and director of the Bernard and Maxine Platzer Lynn Family Memory and Healthy Aging Program. Alfredo Trento, MD— director emeritus of
Cardiothoracic Surgery, vice chair of Outreach and Business Development for Cardiac Surgery at the Smidt Heart Institute, and the Estelle, Abe and Marjorie Sanders Chair in Cardiac Surgery—received Cedars-Sinai’s Pioneer in Medicine Award for 2021. The annual honor goes to physicians who have played major roles at the medical center and gained national recognition for their accomplishments. Trento is an international leader in minimally invasive heart surgery, particularly robotically assisted repairs of the mitral valve, and is largely responsible for leading Cedars-Sinai’s performance of more heart transplants than anywhere else in the country. Jennifer Van Eyk, PhD, the Erika J. Glazer Chair in Women’s Heart Health and director of the Advanced Clinical Biosystems Research Institute, was listed as one of the top 100 analytical chemists in the world in 2021. The annual list published by The Analytical Scientist celebrates the world’s most influential analytical scientists. Infectious disease specialist Phillip C. Zakowski, MD, received Cedars-Sinai’s third annual Master Clinician Award. The award recognizes a member of the medical staff who has made clinical and research contributions at Cedars-Sinai and in the national or international medical communities.
(continued from page 33) “Trauma is a disease, just like diabetes and colon cancer,” says Eric J. Ley, MD, director of TRP. “We teach students how we use the literature to guide decisions we make as trauma surgeons by involving them in research.” Fierro’s first task with TRP was to collect data on the development of blood clots so doctors could devise strategies to prevent them. “We reviewed patients’ vital signs, medications and medical devices and built a giant database of variables to help uncover meaningful associations,” says Fierro, who had opportunities to formally present her research findings. When she shadowed physicians during their clinical rounds, Fierro wore a short white coat— given to all program participants— over her regular clothes. “That felt really cool,” she says. “Even though most of what the physicians said went over my head, I had a sense of hopefulness that someday I would be part of the conversation.” Fierro was actively involved in TRP throughout her undergraduate career, first as a student and later as a student leader, when Ley charged her with recruiting new TRP participants. “My only requirement is that student leaders select a diverse group of students who aren’t all 4.0 kids,” says Ley, who has invited more than 15 TRP students to serve as co-authors on peer-reviewed scientific papers during his decade at the program’s helm. As part of her work with the program, Fierro led TRP meetings, met one-on-one with surgical residents, presented TRP research at national conferences and gained a big-picture view of what it’s like to be a trauma surgeon. “Once, I shadowed Dr. Ley on his trauma rounds
and saw a patient who had just had a craniotomy—part of his skull was missing,” she says. If she had any lingering doubt, that experience confirmed her desire to pursue a career in trauma medicine. Since Fierro didn’t know anyone in the medical field, she relied on Ley and her fellow TRP members to guide her through the medical school application process. That extra support is vital. Data shows that more than 60% of TRP graduates go on to medical school. “The program is really what the students make of it—and most students are remarkably successful,” Fierro says. “It offers them the opportunity to explore medicine in a way that usually isn’t an option for those without a medical degree.” TRP was just the beginning of Fierro’s time at Cedars-Sinai. During her fourth year of medical school at the University of Southern California, she participated in a rotation at Cedars-Sinai and then matched here. Now Fierro serves as a third-year general surgery resident mentoring the next generation of TRP students—and has earned a longer white coat. Her research focuses on whether chest compressions for resuscitation become futile after a certain age or whether high mortality after chest compressions occurs for all ages. “Successful trauma care hinges on collecting data so we can achieve better outcomes for all of our patients, regardless of their demographics and socioeconomic status,” Fierro says. “It’s rewarding to be part of a team that sees every patient as a human being who is in pain and who also has family members who love them—especially when I know that we can make a difference for people like the ones who surrounded me when I was growing up.”
SUMMER 2022 | DISCOVERIES |
35
Sarah Vasen: A Pioneer in Obstetrics and Hospital Leadership Sarah Vasen, MD, has several firsts to her name. In 1904, she became the first Jewish woman to practice medicine in Los Angeles. In 1906, she was the first female executive appointed at Kaspare Cohn Hospital, which later became Cedars-Sinai. Vasen was a female physician specializing in gynecology and obstetrics at a time when the field was overwhelmingly led by men. “Vasen was one of the first female OB-GYNs to practice in Los Angeles, but we shouldn’t forget that women had been practicing midwifery years before men
36 | DISCOVERIESMAGAZINE.ORG
took over and ‘created’ this specialty,” says Kimberly Gregory, MD, MPH, director of the Division of Maternal-Fetal Medicine at Cedars-Sinai and the Helping Hand of Los Angeles–The Miriam Jacobs Chair in Maternal-Fetal Medicine. “Vasen was a pioneer female OB-GYN physician, and now women dominate the field.” Beyond her medical practice, Vasen’s stewardship also paved the way for women holding leadership roles within healthcare organizations. “Women bring a different style and way of thinking to leadership, which helps to
create better organizations due to their diversity of thought and approach,” says Nicole Leonard, JD, MBA, vice president and associate dean of research at CedarsSinai. “Given how groundbreaking it was for Vasen to have been a clinician, let alone a healthcare executive, her unique perspective certainly informed and shaped the inclusive culture of CedarsSinai that still persists over 100 years later.” After leaving Kaspare Cohn Hospital in 1910, Vasen opened a private maternity practice and spent much of her time volunteering to help low-income members of Los Angeles’ growing Jewish community. “The board members of the Kaspare Cohn Hospital—themselves marginalized as Jewish—helped empower Vasen to care for the community,” says Shelly Lu, MD, director of the Karsh Division of Gastroenterology and Hepatology at CedarsSinai and the Women’s Guild Chair in Gastroenterology. “Because Cedars-Sinai grew from Kaspare Cohn, these are our foundational stories. They are brilliant inspirations as we work to overcome barriers to serving the community.” Vasen’s legacy continues at CedarsSinai to this day. “Vasen’s leadership as both a physician and senior hospital administrator clearly contributed to the rise of modernday Cedars-Sinai’s success,” says C. Noel Bairey Merz, MD, director of CedarsSinai’s Barbra Streisand Women’s Heart Center at the Smidt Heart Institute and the Irwin and Sheila Allen Chair in Women’s Heart Research. “We recognize her inclusion as making the overwhelming case for diversity in the workplace.” To learn more about the history of medicine and the history of Cedars-Sinai, engage with our Program in the History of Medicine, which can be found at cedarssinai.edu/education/history.
CEDARS-SINAI MEDICAL LIBRARY CONSERVANCY
A Look Back
CEDARS-SINAI NONPROFIT ORG. U.S. POSTAGE
PAID Cedars-Sinai
PERMIT NO. 22328
6500 Wilshire Blvd., Suite 1900
LOS ANGELES, CA
Los Angeles, CA 90048
In This Issue 6 Q+A A Pediatrics Leader Looks Ahead
22 The New Lung Cancer Landscape
Ophir Klein, MD, PhD, is executive director of Cedars-Sinai Guerin Children’s, a new initiative to serve pediatric patients. He explains how understanding embryos could offer answers for illnesses in children and adults.
Breakthroughs in treatment and screening mean more people than ever are surviving the No. 1 cancer scourge. Cedars-Sinai researchers and physicians want more: a cure.
18 MEET Memory Maker
28 Keep On Ticking
With the number of Alzheimer’s patients projected to triple over the next 40 years, Zaldy Tan, MD, MPH, is developing better ways to deliver care to dementia patients while also supporting their caregivers.
In a single decade, minimally invasive valve repair and replacement techniques put longer lives and healthier hearts within reach of thousands of patients. The roots and forefront of this revolution can be traced to the Smidt Heart Institute’s Raj Makkar, MD.
20 LEARN Lessons from a Pandemic COVID-19 brought most of the world to a standstill while it set healthcare workers racing to innovate immediate answers and lasting solutions. Experts share what they learned to help address this pandemic and the next one.
PUB_DISCS22
