Discoveries magazine Summer 2019

Cedars-Sinai • Summer 2019

A RACE AGAINST LIGHTNING THE PREGNANCY DISORDER PREECLAMPSIA CAN STRIKE LIKE LIGHTNING, THREATENING THE LIVES OF MOTHER AND CHILD. A TREATMENT MAY FINALLY BE ON THE HORIZON. P. 30

PLUS BRINGING CANCER PREVENTION TO UNDERSERVED COMMUNITIES P. 36

SCALPEL VS. BULLET: PERSPECTIVES ON GUN TRAUMA P. 22

THE NEW FACE OF MULTIPLE SCLEROSIS P. 24

Cedars-Sinai

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

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This publication is for informational purposes only and should not be relied upon as medical advice. It has not been designed to replace a physician’s medical assessment and medical judgment. Always consult first with your physician regarding anything related to your personal health.

ABOUT CEDARS-SINAI

CEDARS-SINAI MAINTAINS THE

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

FOLLOWING GOALS FOR BIOMEDICAL RESEARCH:

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

Cedars-Sinai is fully accredited by the Association for the Accreditation of Human Research Protection Programs Inc. (AAHRPP) for assuring protection for human subjects during research. Cedars-Sinai was the first institution in California to receive this designation. AAHRPP is a Washington, D.C.-based nonprofit organization that uses a voluntary, peer-driven educational model to accredit institutions engaged in research involving human subjects.

Cedars-Sinai does not discriminate against any person on the basis of race, color, national origin, disability, age or sex in admission, treatment or participation in its programs, services and activities, or in employment. For further information about this policy, contact the public civil rights coordinator, at 310-423-7972.

SUMMER 2019

Contents

In This Issue

Misha Gravenor

36 Not Lost in Translation Cultural barriers once kept Myong Shim Lee from vital healthcare services—and such obstacles remain in place in many underserved communities. Now, Cedars-Sinai investigators are opening lines of communication to help more people get needed care.

THE EXPERTS YOU TRUST, NOW IN YOUR NEIGHBORHOOD. L.A.’s best doctors are closer than ever, with locations in more than 20 communities in the greater Los Angeles area. So whether you’re in need of a simple checkup or more specialized care, Cedars-Sinai is close by for you and your family.

•

SPECIALTY CARE

1-800-CEDARS-1

•

URGENT CARE

cedars-sinai.org

Most insurance plans accepted.

•

EMERGENCY CARE

© 2019 Cedars-Sinai

PRIMARY CARE

Contents

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Departments 5 NEWS & NOTES The connection between smell and metabolism; a genetic factor fueling aggressive prostate cancer; a new, minimally invasive device to heal patients with aortic aneurysms; activating stem cells to regenerate tissue; a surgical strike against stroke; predicting emotional and cognitive health in early childhood; and more

18 MEET THE DNA DECODER Genetic counselor John Lee, MS, of the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, discusses gamechanging advances related to genes, the proactive power of DNA testing—and why consumers may be buying bad science.

20 LEARN DATA HEROES Get to know CedarsSinai’s bioinformatics champions, who dig through vast data sets to distill meaningful

patterns from our genes, tissues and behaviors. Their research is informing new ways to predict, identify and treat disease.

22 THINK FRONTLINE CARE Cedars-Sinai trauma surgeons share what it’s like to treat gunshot victims, their medical perspectives on the increase in gun-related deaths—and how they maintain objectivity as they address this growing public health problem.

41 FACULTY NEWS Three female residents forge futures in the historically male-dominated specialty of neurosurgery; awards and grants.

44 WHAT’S IN YOUR OFFICE?

Features

Evan Zahn, MD, gives Discoveries a glimpse into his inner sanctum, sharing treasures from his travels and explaining his admiration for Ron Burgundy.

24 No Time for MS Scientists don’t know what causes multiple sclerosis or how to stop its attack on the nervous system. But more sensitive diagnostic tools and powerful new medications are helping patients like Amy Fire get on with their busy lives.

30 A Race Against Lightning The pregnancy disorder preeclampsia can strike in a flash, endangering both mother and child. A dream team at Cedars-Sinai is determined to render this disease—a leading cause of maternal mortality—a relic of the past.

8 COVER ILLUSTRATION Christina Chung

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From the Dean

What Defines Us

A

For Cedars-Sinai, protecting patients’ wellbeing is paramount, and meeting their needs is priority No. 1.

t Cedars-Sinai, we strive to expand the boundaries of scientific knowledge and leverage our research to advance medical care. Yet, what defines us is not simply our success in pioneering new treatments or innovating revolutionary techniques. Central to our mission is an emphasis on supporting the individuals and families who rely on us for them to thrive.

I walk the hallways of Cedars-Sinai in the evening hours, and am often struck by the scenes I see unfolding there. Our patients’ faces tell a story. They may be anxiously anticipating a biopsy result, or contemplating a major, complex surgery in the morning—waiting for a new heart or liver or kidney, and not knowing whether this will be their last evening on Earth or not. But in addition to the fear and uncertainty, other emotions are on display: trust, confidence, a feeling of security and an understanding that, for Cedars-Sinai, protecting patients’ wellbeing is paramount, and meeting their needs is priority No. 1.

This issue of Discoveries shares some of their stories, highlighting the human touch that makes Cedars-Sinai so special. Reading about each patient’s experience, it becomes clear that he or she could just as easily be you or me—or our spouses, sisters, brothers, children, parents or grandparents.

The narratives are universal, and they are unanimous in showcasing the singular benefits of Cedars-Sinai’s signature compassionate care.

These pages typically chronicle the many ways in which our talented physicians and investigators are raising the bar for extraordinary medical discovery. In this issue, you will also see reflected the warm, engaged, attentive, nurturing environment that helps make us a top-tier healthcare destination for patients and their families from around the world.

We recognize and appreciate the diverse groups of talented and passionate stakeholders whose work has enabled us to build this remarkable community.

It takes a complex network of professionalism and compassion to deliver both high-impact research and industry-leading care and remain sensitive to the private and emotional needs of our patients.

Cedars-Sinai is a partnership in every sense of the word. I encourage our readers to join us in charting the future of Cedars-Sinai. We respect the emotional toll disease can take on our patients and, together, we are committed to continuously improving their outcomes and saving countless lives every single day.

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

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News & Notes Summer 2019

6 STATS | 10 TECH CORNER | 16 GOOD TO KNOW | 17 WORD

The Nose Knows

Clint Blowers

Smell and metabolism could be connected.

Hunger can activate your sense of smell, but is there a relationship between your nose and your weight? New research at Cedars-Sinai suggests that what we smell might affect how our bodies process food.

In one recent study, investigators uncovered a connection between olfactory neurons, which control smell, and metabolism, the body’s process of converting food into energy. Celine Riera, PhD, found that mice without olfactory neurons—no sense of smell—ate the same amount and type of food as normal mice but remained leaner. In mice without functional sniffers, Riera found that the hypothalamus—the part of the brain that regulates energy, balance and appetite—perceived food differently.

“We’re very excited about this finding, which may give us the

opportunity to better understand the pathways of obesity in humans,” says Riera, an investigator in the Cedars-Sinai Center for Neural Science and Medicine.

Another study aims to discover whether the reverse relationship between smell and metabolism could exist.

Shehnaz Hussain, PhD, is investigating non-alcoholic fatty liver disease, a condition linked to obesity and diabetes that can lead to cirrhosis and cancer of the liver. An upcoming study will regulate the diets of people with the disease to explore, among other functions, whether a change in food intake can affect sense of smell.

Fortunately, despite our bodies’ and brains’ complicated relationship to food, aromas still have zero calories.

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Dangerous Driver Investigators reveal a genetic factor fueling aggressive prostate cancer.

master regulator of lethal prostate cancer that may be a useful therapeutic target for patients whose cancer spreads and evades hormone therapy,” says Michael Freeman,

STATS : A NEW ERA IN CANCER RESEARCH AND CARE Cancer has been recognized as a disease for thousands of years, but investigators only began making significant strides in research to fight it a few centuries ago. In 1775, fireplace soot was linked to cancer in chimney sweeps. Later, other environmental hazards as well as inflammation, heredity and radiation were identified as risk factors.

Today, with the decoding of the human genome, cancer research has entered a new era as Cedars-Sinai investigators develop increasingly advanced methods for precision diagnosis and treatment.

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PhD, co-director of the Cancer Biology Program in the Samuel Oschin Comprehensive Cancer Institute, and the Ben Maltz Chair in Cancer Therapeutics.

160,000

outpatient visits in 2018, making Cedars-Sinai Cancer one of California’s busiest treatment facilities (including more than 37,000 infusions and some 18,000 radiation treatments)

Raul Arias

Men whose prostate cancer metastasizes and resists hormone therapy face a poor prognosis, with fewer than a third living five years past diagnosis. But laboratory findings may lead to ways to rein in cancer’s rampage, according to research led

by Cedars-Sinai.

The investigators identified a driver of aggressive prostate cancer in animal models and also found a molecule that could potentially attack it. Analyzing patient genetic and molecular data, the team found elevated activity of the molecule ONECUT2 (OC2)—needed by the body to manufacture certain proteins—in tumors of patients whose prostate cancer resisted hormone therapy.

Their experiments also identified a compound that counteracted OC2 to significantly reduce the size of prostate cancer metastases in mice.

“Our research suggested that OC2 is a

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Egle Plytnikaite

Battle of the Bulge

A Cedars-Sinai vascular surgeon was the first in the world to use a minimally invasive device to heal patients with aortic aneurysms. The aorta, the body’s largest artery, delivers blood from the heart to

other organs and to limbs. If an aneurysm—a weakening or bulging—develops, it can become life-threatening and require surgery. However, a patient’s anatomy or overall health may preclude an open-chest procedure.

Ali Azizzadeh, MD, director of Vascular Surgery at the Smidt Heart Institute, demonstrated the effectiveness of a recently approved stent graft device, the Valiant Navion, which is delivered through a blood vessel in the groin then into the aorta, where it repairs the aneurysm. Compared to other technologies, the stent graft can travel through smaller, curvier vessels and better adjust to a patient’s anatomy.

“Prior to approval from the Food and Drug Administration, patients with many types of aneurysms and aortic conditions had limited treatment options,” Azizzadeh says. “Now, surgeons can fix complex problems of the aorta without open surgery.”

The first patient to undergo this pioneering procedure was Nancy Angelino, age 85. “This was a difficult surgery, but I knew I was in good hands,” she says. “I feel very lucky to have benefited from this new and improved surgical technique and for the great doctors who cared for me.”

7% 76,000 9 of hospitals won an Outstanding Achievement Award from the American College of Surgeons’ Commission on Cancer program— with Cedars-Sinai among this elite group

square feet of new dry and wet laboratory space and 44,000 square feet of new clinical space to expand capacity to care for cancer patients

hospitals, including Cedars-Sinai, earned Magnet Recognition from the American Nurses Credentialing Center five times in a row SUMMER 2019 | DISCOVERIES |

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The nation’s third-leading cause of cancer-related deaths, pancreatic cancer is a slippery foe that arrives later in life, often in patients with no history of smoking, drinking or other harmful habits. Its unpredictability adds to its deadliness, as symptoms seldom appear in early, more treatable stages.

One bright spot is that survival rates have increased from 4% to 9% over the past five years.

At Cedars-Sinai, Andrew Hendifar, MD, medical director of Pancreas Oncology, and Stephen J. Pandol, MD, director of Basic and Translational Pancreas Research, are taking a variety of paths toward greatly improving those percentages.

Hendifar and colleagues are expanding patient options through Cedars-Sinai’s participation as a clinical trial site of the Pancreatic Cancer Action Network’s Precision Promise initiative, dedicated to doubling survival by 2020. The initiative complements a multisite trial to prevent a muscle-wasting condition called cachexia by trying to determine whether optimizing nutrition, physical activity and use of an anti-inflammatory improves outcomes, Hendifar says.

The Earlier, the Better

Cedars-Sinai collaborates with investigators around the globe to identify people at risk and determine who actually has early pancreatic cancer, Pandol says. “We do this using blood and urine tests, and we’re improving how we use CT scans and MRIs to find cancer early, when it’s easier to miss it.”

Drugs Target Tough Problems

The investigators are developing medications to prevent both metastasis of cancer and drug resistance. “We started with two agents combined in a test tube and then studied in animal models, and that positively affected both problems,” Pandol says.

Pursuit of Immunotherapies

Thus far, immunotherapy hasn’t worked well for pancreatic cancer, Pandol says. “This cancer puts up a ‘screen’ so the natural immune system can’t attack it,” he adds.

Hendifar is trying new combinations to address this problem.

Stem Cell Science

The team is gearing up to obtain stem cells from patients with cancer and relatives who may carry risk factors. “We will investigate how to identify those at risk, and how to reverse it,” Pandol says.

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Doctors can now receive accredited training in gastrointestinal (GI) surgery techniques via a fully immersive virtual reality (VR) experience, thanks to a pioneering partnership between Cedars-Sinai and medical streaming company GIBLIB. A VR headset shows trainees a 360-degree panoramic perspective of the operating room, complete with multiple angles, including the physician’s point of view, and digital overlays such as patient imaging.

“We are excited to bring Cedars-Sinai medicine virtually to any doctor at any medical facility,” says Harry Sax, MD, executive vice chair of the Cedars-Sinai Department of Surgery.

“With this technology, other medical professionals can learn our advanced techniques and procedures and, ultimately, deliver excellent care to patients across the country.”

One VR training, the Essential GI Surgeries course, offers 25 hours of high-definition, fully narrated surgical procedures that feature the latest in laparoscopic and robotic techniques demonstrated by Cedars-Sinai experts. Healthcare professionals can access the course by subscribing to giblib. com.

Gary Niell

Pancreatic Cancer Battlefield

Virtual Reality, Real Training

Precision Promise

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Heart Rhythm Revelations

Research shows increased risks of sudden cardiac arrest for patients with certain conditions—and that Mondays get a bad rap.

Recent studies led by Sumeet Chugh, MD, associate director of the Smidt Heart Institute and the Pauline and Harold Price Chair in Cardiac Electrophysiology Research, unveil clues to factors that heighten the danger of sudden cardiac arrest.

Peak Cardio

Heart experts have long believed weekday mornings—especially Mondays—to be the peak danger zone for sudden cardiac arrest, but Chugh’s research shows this is no longer the case. However, the news is not necessarily good, as cardiac arrests are now considered equally possible at any time.

“Stress is likely a major factor,” he says. “We now live in a fast-paced, ‘always on’ era.”

Other findings are more positive, including promising outcomes from new treatment strategies in high-risk patients as well as corrections for how past studies inadequately measured time of death.

Ivan Canu

Deadly Beat

Smidt Heart Institute investigators discovered that patients with the most common type of heart failure are twice as likely to have an untreatable form of lethal heart rhythm responsible for sudden cardiac arrest—heart failure with preserved ejection fraction (HFpEF). HFpEF is not only responsible for about half of all cases of heart failure, but also is more likely to strike women than men. The findings suggest that surgically implanted defibrillators are less effective against HFpEF than other types of heart failure. Additional studies

are needed to determine which high-risk patients are most likely to benefit from defibrillator implantation.

Risk Management

Patients with multiple sclerosis (MS) face five times the risk of sudden cardiac arrest compared to the general public, according to Chugh. While the reasons for the disparity need further investigation, the brain’s established links with cardiac function could be influencing the heart’s electrical function in MS patients.

In another study, Chugh and his team found that patients with left ventricular hypertrophy (LVH)—an enlargement and thickening of the walls of the heart’s main pumping chamber—are also at elevated risk of sudden cardiac arrest. However, diagnosing those in the most danger had proved elusive.

Now, using an electrocardiography risk score, clinicians can better identify patients with intermediate or high-risk LVH. Another of Chugh’s projects found that obesity and LVH are each independent predictors of sudden cardiac arrest.

5 The data for these studies came from the Oregon Sudden Unexpected Death Study—a comprehensive project headed by Chugh that is now in its 16th year.

“Because sudden cardiac arrest is usually fatal, we have to prevent it before it strikes,” he says.

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To Err Is … Neural The neurons that help us recognize our errors may hold the key to improving treatments for psychiatric and mental disorders.

When servers deliver our food with a hearty “Enjoy your dinner” and we absentmindedly reply, “You, too,” we tend to realize immediately that we misspoke.

Now, thanks to a Cedars-Sinai study, we know which neurons in the brain enable us to catch such momentary glitches.

The identification of these brain policers—known as “error neurons”—could open the way to discovering treatments for schizophrenia, autism, memory disorders and other conditions that disrupt our brain’s ability to self-monitor.

“One of the brain areas known to be important for self-monitoring is the medial frontal cortex,” says principal investigator Ueli Rutishauser, PhD, Board of Governors Chair in Neurosciences. “But how exactly this process works—and why it fails—has been poorly understood.”

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The study drew from patients undergoing surgical treatment for drug-resistant epilepsy. Using electrodes already placed in the subjects’ brains as part of their therapy, the investigators evaluated patients’ neuron responses to the Stroop test, which measures reaction time. Participants are asked to say the color of a word that doesn’t match its name.

For example, the word “green” is printed in red ink. When subjects misidentify a color, they tend to notice their mistake right away.

“These electrodes allowed us to measure electrical activity of individual neurons and identify those that increase or decrease their activity when an error is detected,” says Adam Mamelak, MD, director of the Functional Neurosurgery Program.

The neurons’ activity generates an electrical signal well-known to neurologists as error-related negativity. “If you have someone perform a task where they knowingly make mistakes, you will detect that signal,” Mamelak explains. The team aimed to demonstrate how the error neurons may work in concert to generate it.

Pinpointing these neurons previously proved challenging because error-related negativity casts a broad signal, “as if you’re looking out at the ocean and just see a big wave of water,” Mamelak adds.

“The new research allowed us to see the water molecules and the wind that generate the wave.”

Certain mental illnesses have long been associated with a modified error-related negativity response but the reason for this has remained unclear. People with obsessive-compulsive disorder have largerthan-normal responses, indicating that their brains are over-monitoring for errors, while patients with schizophrenia often exhibit a reduced response.

“This new work pinpoints the exact neurons that likely are firing abnormally in people with these disorders,” Mamelak says.

The project was led by first author Zhongzheng Fu, a graduate student in the Rutishauser Laboratory. Rutishauser’s and Mamelak’s laboratories focus on understanding brain mechanisms that support cognitive functions such as error monitoring, which could one day lead to meaningful therapies for a variety of mental health conditions.

Giulio Bonasera

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Prescription for Safety Pharmacists play key role in caring for patients with complicated medication regimens.

The number of Americans taking prescription medications—and the amount they consume—has skyrocketed in the last two decades. Juggling all these prescriptions is complicated, and patients risk their health if they drop the ball. Cedars-Sinai pharmacists have launched multiple initiatives to protect patients in the hospital and after they return home.

Bedside Medication Delivery Patients can receive prescriptions in their hospital rooms so that, when they leave Cedars-Sinai, their medications go with them, eliminating a stop at the drug store.

Pharmacy staff members review prescriptions with patients and also share information about financial assistance, so expense won’t stop someone from filling a prescription.

Tallulah Fontaine

Not All Wet An advanced Cedars-Sinai water treatment facility has slashed use of city-supplied water by dipping into a natural aquifer under the hospital.

The project saves 29 million gallons annually, the equivalent of supplying 267 single-family homes with water for a year.

Los Angeles Mayor Eric Garcetti toured the underground water system with executives from the Los Angeles Department of Water and Power and the Metropolitan Water District of Southern California, highlighting Cedars-Sinai’s system as an example of innovative conservation. “At a moment when

climate change and drought are becoming the new normal, the Cedars-Sinai treatment facility shows how property owners can help us better withstand the effects—through a strong commitment to conservation and sustainable design,” Garcetti said.

In addition to its conservation benefit, the program solved a watery problem. The aquifer threatened facilities with rising water during rainy seasons. By tapping this groundwater source, Cedars-Sinai eliminates potential flooding and saves nearly $365,000 a year.

“Frequent medical breakthroughs mean that more of the patients we see are taking myriad medications for a wide range of diseases. We ensure that a patient’s treatment plan is carried out the way it was intended.

It’s an expansion of the familiar role of a pharmacist in a community practice.”

Rita Shane, PharmD, Chief Pharmacy Officer

Medication Education Pharmacists ask those who have undergone organ transplantation, who are taking more than 10 medications or who have cardiac conditions to explain their medication regimens in their own words. The pharmacists then counsel the patients to make sure they understand the importance of taking their medications. These high-risk patients also receive check-in phone calls from pharmacists within three days of returning home.

Drug History Pharmacists and pharmacy technicians obtain medication histories for high-risk patients and pharmacists evaluate all prescription orders. Their efforts help avoid errors, reduce drug-to-drug interactions and ensure dosages are safe based upon each patient’s conditions.

Antibiotic Monitoring Hospital physicians partner with pharmacists to monitor antibiotic use, as overuse can lessen the drugs’ effectiveness. Meanwhile, pharmacists trained in infectious diseases catch early signs of antibiotic resistance.

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N & N TECH CORNER

Healed From Within Stem cells regrow damaged tissue.

1. THE NEED Wounded soldiers and civilians as well as accident survivors often undergo painful surgeries that may still fail to return limbs to normal function.

2. THE GOAL Devise a way to encourage the body to regrow its own tissue.

3. THE TECHNIQUE By injecting microbubbles mixed with a patient’s DNA into the affected area and then applying ultrasound waves, the patient’s stem cells can be activated to regenerate missing tissue and heal injuries without invasive surgery.

4. THE INNOVATORS Zulma Gazit, PhD, (left), and Dan Gazit, DMD, PhD, (right), co-directors of the Skeletal Regeneration and Stem Cell Therapy Program; and Gadi Pelled, DMD, PhD, (center), assistant professor of Surgery

5. THE SUPPORT The Department of Defense and National Institutes of Health have awarded nearly $8 million to CedarsSinai to advance the technique—including funding to help take it to human clinical trials.

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“The approach of activating the patient’s own stem cells could provide a platform for myriad clinical applications, such as heart and skin regeneration,” says Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine.

Peter O’Toole

6. THE FUTURE

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Surgical Strike Against Stroke Advanced technique for highrisk patients creates new paths for blood flow to the brain.

One of the most common causes of stroke is atherosclerotic disease, in which plaque buildup narrows the arteries leading to the brain. A Cedars-Sinai-led clinical trial tested the effectiveness of a surgical technique tongue-twistingly called encephaloduroarteriosynangiosis (EDAS for short) in decreasing the rate of stroke recurrence and fatalities for patients with severe atherosclerosis.

EDAS involves rerouting arteries from the scalp and membranes that cover the brain, to segments

of the brain at risk of stroke. Over time, new blood vessels form, creating fresh paths for blood and oxygen to reach the brain.

Headed by Nestor R. Gonzalez, MD, director of the Cedars-Sinai Neurovascular Laboratory, and funded by the National Institute of Neurological Disorders and Strokes, the trial produced encouraging results. After one year, just 9.6% of patients who had the surgery experienced another stroke—compared to 21.2% in a control group with treatments limited to intensive medical management.

Gonzalez and his team are developing a Phase III clinical trial across numerous institutions to further test the potential of EDAS.

Pancreatic Protector

Edmon de Haro

New drug blocks cancer growth and offers protection against resistance to treatment.

A new drug can prevent the most common type of pancreatic cancer from growing and spreading in laboratory mice, according to a study led

by Cedars-Sinai.

“If the results are confirmed in humans, we could have a drug with the potential to significantly extend the lives of patients with pancreatic ductal

adenocarcinoma [PDAC], which is very difficult to treat,” says the study’s lead author, Mouad Edderkaoui, PhD, a scientist at the Samuel Oschin Comprehensive Cancer Institute.

Pancreatic cancer is the third-leading cause of cancerrelated deaths in the United States, with a five-year survival rate of just 9%.

PDAC accounts for 95% of patients diagnosed with the disease. It has remained hard to treat because the cancer cells prompt healthy cells to produce scar tissue that blocks anticancer agents from entering the pancreas, Edderkaoui explains.

The cellular interaction also stimulates local tumor growth and metastasis.

The investigations showed that the drug, Metavert, could also stop patients from developing resistance to current pancreatic cancer chemotherapies. In rodents, the drug

increased the survival rate by approximately 50%.

“Patients may respond to treatment for a time, but then the cancer becomes ‘smart’ and fuels resistance to chemotherapy,” Edderkaoui says.

“Metavert targets this activity, boosting the positive effects of the radiation and the most commonly used chemotherapy agents,” he adds.

The investigators currently are developing a version of the drug to test in humans.

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Escape Artists

A new biomarker provides a first alert for the most common form of cardiac failure.

Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of all cardiac failure cases and affects more than 6.5 million Americans—predominantly women—each year. Thanks to the discovery of a new biomarker by a Smidt Heart Institute team, HFpEF can now be diagnosed earlier.

Called cBIN1, the biomarker enables a simple blood test to reveal whether a patient’s heart is making enough of a specific protein. Decreased levels of the protein could signal the initial stages of heart failure.

Previously, clinicians had to wait for symptoms such as fatigue and shortness of breath to appear, then needed an echocardiogram to measure how well the heart relaxed.

“By the time heart failure symptoms develop, the critical window for corrective therapy has typically closed,” says Robin Shaw, MD, PhD, principal investigator and the Wasserman Foundation Chair in Cardiology in honor of S. Rexford Kennamer, MD. “Our discovery

allows us to not only diagnose the disease sooner but also to treat patients before that critical period of early intervention for lifesaving care has closed.”

The ability to administer the new blood test on an outpatient basis is another advantage of the biomarker, according to Eduardo Marbán, MD, PhD, director of the Smidt Heart Institute and the Mark Siegel Family Foundation Distinguished Chair.

“This discovery will allow the most at-risk patients—including older patients and those with high blood pressure, diabetes or high cholesterol—to be checked during an annual exam by their primary care physician,” he says. “This could serve as a critical tool for preventive heart care.”

As next steps, the investigators plan to identify populations in which the biomarker could be useful, including sex-based differences, those who have undergone a heart transplant or valve replacement, as well as individuals with no known heart disease or risk factors.

Neil Webb

A deadly virus is loose—and your team has only 45 minutes to find a cure.

Meanwhile, researchers monitor your every action from a safe distance.

This sinister-sounding scenario is actually an escape room challenge at Cedars-Sinai, which was designed to study the behaviors of healthcare teams.

The experience, which includes props and special effects, is part of the Gewertz and Cohen Laboratory’s investigations into factors that drive team performance in healthcare.

“Participants can take what they learn in the escape room and apply it to reallife situations,” research scientist Tara Cohen, PhD, explains.

After their time is up, participants discuss where they excelled—and in which areas they could improve. “By understanding the processes that members use when working together, we can develop teams that are more likely to function optimally,” Cohen says.

Telltale Heart

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Pregnant Pause Young women with breast cancer are typically cautioned against having children for fear that elevated estrogen levels from pregnancy might increase the risk of cancer returning or spreading. Cedars-Sinai investigator Philomena McAndrew, MD, is challenging that conventional wisdom.

As a scientist in the international POSITIVE clinical trial, McAndrew is studying whether it’s safe for women who have already been treated for early breast cancer to temporarily pause their antiestrogen maintenance therapy to try to become pregnant.

The trial specifically focuses on women who have had hormone-receptor-positive tumors, meaning the cancer cells grow in response to estrogen or progesterone.

“Results of studies show that these patients don’t have a higher chance of their cancer spreading in comparison to women who have never become pregnant after their breast cancer,” McAndrew says.

She and her colleagues hope to demonstrate, once and for all, that “young women who have developed breast cancer don’t have to be denied the hope of having a family or more children.”

Organ Failure

Eva Vázquez

Liver transplant waitlists may misclassify high-risk patients.

When the liver is too damaged to function, a transplant can be a patient’s last hope of survival.

But the sickest patients may not be offered a donor organ, according to Cedars-Sinai investigators who helped uncover a gap in the standard method of prioritizing patients on transplant waitlists.

Medical professionals rely on the Model for End-Stage Liver

Disease (MELD) score to determine who is most likely to die from complications related to liver failure. But according to the new study, the MELD score does not fully determine prognosis in certain patients who have acute-on-chronic liver failure grade-3 (ACLF-3), a syndrome in which the liver’s sudden deterioration is accompanied by multiple other organ failures.

The team discovered that patients with ACLF-3 are sicker than their scores indicate. MELD only accounts for liver and kidney dysfunction and not additional circulatory, respiratory or neurologic breakdowns that occur in these patients.

“Time is of the essence because it is clear that survival declines with increased waiting time for these patients,” says

Vinay Sundaram, MD, director of Hepatology Outcomes Research.

The team also found that, when transplants were performed within 30 days after being waitlisted, ACLF-3 patients’ one-year post-transplant survival rate was more than 80%—similar to patients without the syndrome.

The research could one day help improve the waitlist system.

SUMMER 2019 | DISCOVERIES |

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N & N GOOD TO KNOW

Stem Cells: Myths and Musings

Myth: All stem cells are created equal.

Reality: “I correlate the power of stem cells with the degree of horsepower in an engine,” Sareen says, comparing types of stem cells to classes of automobile.

SPORTS CAR: These supercharged models

include embryonic stem cells and induced pluripotent stem cells (iPSCs). Scientists create the latter by reprogramming adult skin or blood cells (told you we’d get to it).

Powerful as a Ferrari, these beasts can differentiate into all types of body cells—from kidney to bone.

MUSCLE CAR: Mesenchymal stem cells,

usually taken from bone marrow, are like a stylish Mustang. These high-performance rides can produce a somewhat limited category of cells, including blood cells, cartilage and bone.

LUXURY SEDAN: Adult stem cells can replace themselves—such as a cardiac cell begetting heart tissue—but lack the horsepower to differentiate into other cell types.

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Myth: Stem cell injections trigger regeneration.

Myth: Cord blood is vital for your baby’s future.

Reality: “People tend to think stem cell injections will completely replace missing or damaged cells. Not so,” Sareen says.

The main activity of most stem cell injections is to suppress immune reaction, providing temporary relief, but not a cure, for conditions like joint pain. Sareen cautions against clinics advertising injections as a cure-all, as most stem cell transplants are only available in Food and Drug Administration-approved clinical trials.

Reality: It’s like earthquake insurance. If affordable, it can’t hurt to bank cord blood after birth, but it will likely go unused.

However, for those with a family history of blood diseases, storing cord blood is a good idea. “Cord blood is the purest raw material source to create induced pluripotent stem cells, because a newborn hasn’t lived life and seen stress and L.A. smog.

Therefore, gene mutations haven’t accumulated,” Sareen says.

Myth: Embryos are the primary source of cells for research.

GENERATING THE FUTURE

Reality: iPSCs have almost eliminated the need for embryonic stem cells in the lab.

“An advantage of iPSCs is that you can make a cell line of limitless supply that can be turned into any individual- and organspecific cell. All we need is a blood sample to make them—and then that patient doesn’t need to worry about tissue rejection,” Sareen says, though he notes their safety for clinical use is still being tested.

The next generation of medicine will arrive courtesy of a combination of genetic engineering and powerful cell therapy, Sareen predicts. He points to a new form of cancer immunotherapy known as CAR T-cell therapy, in which a patient’s immune cells are reprogrammed to attack their disease.

“The knowledge we are gathering now eventually may help us eliminate cancers and regenerate organs,” he says.

Dan Page

Stem cells offer epic possibilities—lab-grown organs, injections to erase catastrophic injuries and cures for everything from Alzheimer’s disease to blindness. As with any young science, misconceptions abound.

So Discoveries asked Dhruv Sareen, PhD, director of the Cedars-Sinai Induced Pluripotent (don’t worry, we’ll explain that, too) Stem Cell Core Facility to separate myth from reality.

N&N

Wired for Life Infant brain circuitry predicts emotional and cognitive health in early childhood.

Nearly 15% of U.S. children between the ages of 2 and 8 are affected by mental, behavioral or developmental conditions such as autism and attention deficit disorder. By examining growth rates in infants’ brain circuitry, investigators have discovered ways of identifying the potential for these issues earlier.

“Using the functional connectivity of infants’ brains to predict emotional and cognitive outcomes could become a powerful tool to identify problems early on and design effective treatment plans,” says

Wei Gao, PhD, director of Neuroimaging Research at the Cedars-Sinai Biomedical Imaging Research Institute and co-senior author of the study with a colleague from the University of North Carolina.

The bicoastal team built on earlier research in which they performed MRI scans on more than 1,000 healthy infants to examine how and when connections developed between the amygdala, which regulates emotions, and the rest of the brain. The new project evaluated 223 of those children at age 4 and confirmed that

emotional circuit development during infancy affects children as they grow up.

The next step will be to establish more comprehensive models to forecast a wider variety of developmental outcomes during and beyond early childhood. The team also plans to apply the model to groups at risk for developmental disorders, including babies born prematurely and those who had prenatal drug exposure.

The study received funding from the National Institutes of Health and from Cedars-Sinai Precision Health.

WORD:

MISOPHONIA /mis-oh-FOH-nee-uh / Definition:

Taylor Callery

The literal meaning is “hatred of sound.” More specifically, it refers to the noises that trigger anger, anxiety or other negative responses—sounds most listeners would consider normal and unobtrusive.

The next time someone recoils as you masticate a meal, try not to take offense—that person might be a misophonic. Once known as “sound rage,” this brain-based condition can be set off by such everyday sounds as chewing, typing and even breathing.

Context is key. For example, a mother might have no reaction to hearing her child eat but feel distress during meals with anyone else. Sights and smells can also be triggers. Misophonia needs research attention. No cure exists, but sound therapy, supportive counseling and—sometimes—medication can be helpful in coping with it.

SUMMER 2019 | DISCOVERIES |

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Meet

Q A &

The DNA Decoder: John Lee, MS

hereditary should request one, too. Genetic assessment also can help patients determine what treatments may be most effective, their risk of developing other cancers and whether family members have an increased cancer risk.

By Carrie St. Michel

A: Genetic testing can reveal really important information that someone might not otherwise know. A husband and wife I recently worked with are a good example. Their daughter was diagnosed with breast cancer in her 30s, which is younger than average, so they requested genetic testing.

Cancer runs in the husband’s side of the family and his relatives carry genetic mutations related to breast cancer, so we assumed he would test positive for a mutation. He didn’t, but his wife did. As a result, she went immediately from bystander to patient. She’s since had surgery to reduce her ovarian cancer risk.

Our assessments determine whether a patient is a carrier of a hereditary cancer syndrome and whether they’re likely to develop a certain type of cancer themselves. The tests also inform medical follow-up. For example, if a woman tests positive for BRCA1 or BRCA2, which are inherited gene mutations responsible for about 5–10% of breast cancers and roughly 15% of ovarian cancers, we’d recommend additional breast screening and discuss preventive surgical options.

A program manager and genetic counselor at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, John Lee, MS, discusses game-changing advances related to genes, the proactive power of DNA testing—and why consumers may be buying bad science.

Q: How did genetic counseling pop up on your career radar—are you from a medical family?

A: My mom is a nurse and my sister’s a family doctor, so I guess I am. But I discovered genetic counseling when I took a genetics class at Rutgers University.

Genetic counseling is a good fit because I really enjoy interacting with patients. I also like keeping my science mind sharp—genetic analysis and staying current on constantly evolving genetic-testing techniques are good ways to do that.

Another reason this career proved to be a super good choice is because that’s how I met my wife, who’s also a genetic counselor. As part of her training, she shadowed some counselors—including me—a couple of times. And here we are.

Q: Who should consider genetic testing?

A: People with a personal or family history of specific diseases should consider it to determine whether they’re at risk for developing the disease or passing on a predisposition to their children. I also recommend genetic testing for certain races or ethnic groups who have a higher incidence of particular conditions.

Sickle cell disease, for example, occurs most frequently in African Americans, and Tay-Sachs disease is more prevalent among individuals of Ashkenazi (Eastern and Central European) Jewish ancestry.

Q: Should some people be evaluated by a genetic counselor as part of their cancer care?

A: Patients diagnosed with cancer at younger ages than is typical, or who have multiple family members with the same type of cancer, could benefit from a genetic evaluation. Patients interested in knowing whether their cancer is

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Q: What can genetic tests determine?

Q: How has the field advanced in recent years?

A: This is a very exciting time in the world of genetics, with the most significant advance being next-generation sequencing. Before this technology existed, it was expensive and time-consuming to identify the genetic information carried in specific genes. Now we can simultaneously sequence millions of genes rapidly—and at relatively low cost.

This has resulted in uncovering hundreds of previously unknown genetic causes of cancer and many other diseases.

Q: Direct-to-consumer genetic testing companies like 23andMe and AncestryDNA do big business—more than 26 million people have purchased at-home DNA test kits. What is the science on these products?

JOHN LEE, MS, Licensed Certified Genetic Counselor Program Manager and Genetic Counselor, Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute When John Lee isn’t helping patients reduce their risk of certain cancers, you’re likely to find him: PLAYING TENNIS

or watching his favorite pro, Roger Federer, play.

LISTENING TO MUSIC,

particularly the Red Hot Chili Peppers’ “Soul to Squeeze.”

TRAVELING

Al Cuizon

Lee’s travel itinerary includes trips to his hometown of Chatham Township, New Jersey, but he also enjoys new adventures. Recent journeys include Japan, South Korea and Alaska. In April, Lee and his wife traveled to Massachusetts, where she ran in the Boston Marathon while he cheered her on.

A: When I first started seeing commercials for these testing services, on one hand, I thought it was cool that genetic testing was being introduced to a mass audience. On the other hand, I wondered what type of information people were going to receive and if the tests could provide actionable results.

The bottom line is: Consumers should be cautious. These home tests don’t provide deep-dive, comprehensive assessments that can inform important medical decisions. And the results are questionable because these companies tend to do surface-level genetic analyses. For

example, when 23andMe assesses a woman’s breast cancer risk, it only tests for three gene mutations. Not only are there thousands of identified breast cancer mutations, but the three it tests for are most commonly found in women of Ashkenazi Jewish ancestry, so testing women outside of that group is largely unproductive.

That’s not good science—though 23andMe does recommend that users speak to a genetic counselor who can help explain the findings and discuss next steps. I hope consumers see that and follow up.

This interview has been condensed and edited.

SUMMER 2019 | DISCOVERIES |

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Learn

Data Heroes Data scientists, hunched over computers and steeped in spreadsheets, are among the heroes of medicine. They study the human body at the tiniest scale, digging through vast data sets to distill meaningful patterns from our genes, tissues and behaviors. The result? A deeper understanding of health that informs new ways to predict, identify and treat disease. Here, we introduce some of Cedars-Sinai’s data heroes.

By CASSIE TOMLIN

•

Vidya Venkatraman

Bioinformatics Director, Advanced Clinical Biosystems Research Institute Venkatraman analyzed hundreds of thousands of blood proteins to uncover a novel predictor of heart disease, early signs of which have eluded traditional scans and tests. She now tracks these biomarkers to monitor patients’ evolving heart health. “Proteins send us messages,” she says. “They’re tiny and immediate indicators of what’s going on that may be missed in the clinic.”

•

Sungyong You, PhD

Assistant Professor of Surgery and Biomedical Sciences Working with a database of the genes of thousands of prostate cancer patients, You trained artificial intelligence to sift through gene expressions, treatments and outcomes, and sort patients into groups based on the aggressiveness of their disease. He is now developing software tools to predict individual responses to drugs and therapies.

•

Stanley Conte, MSN, RN

Associate Director, Smidt Heart Institute Conte’s meticulous data-collecting supported an opportunity for more efficient care: shorter hospital stays for minimally invasive heart surgery patients.

He and Joseph Ebinger, MD, director of Clinical Analytics, led a study of 200 patients who underwent transcatheter

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aortic valve replacement. They found that not all of them needed to stay in the intensive care unit, which had previously been standard practice. The finding trimmed two days off of hospital stays for low-risk patients, resulting in quicker recovery and reduced cost.

•

Arek Gertych, PhD

Assistant Professor, Pathology and Lab Medicine Assistant Professor, Surgery Gertych developed an artificial intelligence tool that recognizes miniscule tumor growth patterns in prostate and lung cancer. He used 800,000 extremely high-resolution digital images of lung cancer tissue to train artificial intelligence to detect structural differences in tumor tissue, which may help determine the severity of the disease. “The computer performs precise analysis of single cells that you simply cannot see with the human eye,” he says.

•

Spencer SooHoo, PhD

Director, Research Informatics and Scientific Computing Core SooHoo’s team funnels millions of patient data points into clinical research that pairs people with investigational treatments. He also co-administers Cedars-Sinai’s contributions to All of Us, a nationwide precision medicine initiative that aims to collect the health information of 1 million people as a resource for scientists seeking to study vast health data.

•

Susan Cheng, MD, MPH, MMsc

Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science Director, Cardiovascular Population Sciences, Barbra Streisand Women’s Heart Center Director, Public Health Research, Smidt Heart Institute Cheng studies how and why women and men age differently on a molecular level, and which tiny compounds might protect people of each gender from health decline.

Carefully investigating biological variables may advance understanding of why some people are more resilient than others. “If we’re ultimately aiming to personalize therapies, the first order of difference is gender,” she says.

•

Talin Haritunians, PhD

Assistant Professor Haritunians studies millions of genetic variations to understand which cause the most severe forms of inflammatory bowel disease, a complex condition. She gleans insights on the disease from a repository of thousands of IBD patients whose genetics have been “read” using small, computer-chip-like arrays. She hopes her genetic research, paired with clinical and lifestyle records, will help identify subgroups of the disease. “My goal is to use genetics to understand what each patient needs to help manage the disease so it’s not so debilitating,” she says.

Drive

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THE R OUNDUP We asked our data heroes 10 not-so-scientific questions that shed light on their secret identities.

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Haritunians

SUMMER 2019 | DISCOVERIES |

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Think

Scalpel vs. Bullet: Perspectives on Gun Trauma As told to CASSIE TOMLIN

T

rauma surgeons are all too familiar with the devastating injuries wrought by gun violence. They rapidly analyze how each bullet has ripped through the human body so that its path of destruction can be healed. They orchestrate lifesaving efforts and cope with the aftermath, whether it be positive or tragic.

In the U.S., firearms kill about 40,000 people each year—nearly as many as road accidents or falls. But while deaths from car crashes have declined, rates of gun deaths are trending upward. “In the 1990s, when I was a resident at Los Angeles County+USC Medical Center, I saw a gunshot fracture nearly every day,” says Charles Moon, MD, director of Orthopedic Trauma.

“Locally, the problem has since gotten better, but now, like the rest of the nation, gun violence is trending upward again.”

The American College of Surgeons Committee on Trauma and similar groups designate firearm violence a public health problem. Here, Cedars-Sinai trauma surgeons share what it’s like to treat gunshot victims, their medical perspectives on the increase in gun-related deaths and how they maintain objectivity on the front lines.

Daniel Margulies, MD

When a bullet hits a major vein or artery, a person can bleed to death in minutes. The national Stop the Bleed campaign, in which Cedars-Sinai participates, trains civilians to save lives in emergency situations like mass shootings.

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Director, Acute Care Surgery Associate Director, Division of General Surgery When a patient comes in with a gunshot wound, the situation can be very chaotic: The patient is in pain or in shock, might be screaming and there might be blood everywhere. Our job is to bring order quickly and stabilize the patient. Every minute until the bleeding is controlled is critical. We talk to the patient and the paramedics to get clues about how to treat the patient, including whether they know what kind of gun was used. The bullets that people and police are using now do more damage than they used to.

Semiautomatic weapons are becoming more common, and these injuries are more lethal and difficult to treat because they produce more bullet holes, and each wound itself can be life-threatening. The amount of violence we’re seeing—mass shootings, suicides and otherwise—is pervasive. These avoidable injuries and deaths also contribute to physician burnout because of the high-stress environment they create.

It is really gratifying to be able to save someone who is dying right in front of you, but it doesn’t always work out that way.

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Semiautomatic firearms, like the AR-15, are modeled after assault rifles designed for military use. Their high-velocity bullets “bounce” around bodies, ripping through organs and bones, and are twice as likely to kill a person compared to other firearms.

Up to 60% of physicians experience exhaustion. Those on the front lines of care, like emergency medicine doctors, are most at risk.

One study, published in the Journal of Surgical Research, found that, of roughly 39,000 suicides considered over 14 years, nearly 60% occurred in states that had more lenient gun legislation.

David Arky

For more than 20 years, Congress has cited the Dickey Amendment in prohibiting the use of federal funds to advocate or promote gun control.

Rodrigo Alban, MD

Associate Director, Surgical Performance Improvement Associate Director, General Surgery Residency Program In 2018, I published studies linking weaker state gun laws with higher rates of suicide and gun deaths in children and young adults. It wasn’t easy because information isn’t reported in a consistent manner. Plus, the Centers for Disease Control and Prevention and the National Institutes of Health considerably limit funding for research about firearm violence. I truly understand the importance of the Second Amendment and support the right to own a firearm legally. Having said that, with the injuries I’ve seen, I believe it’s my responsibility to provide a public health service: looking into the facts of gun violence in our society. Who takes the lead on this work? Who gives voice to these injuries? As researchers, we look for the truth with rigorous, scientifically sound statistical methodology. It is my ethical duty to objectively report the data that I find.

Ara Ko, MD, MPH

Chief Resident, Trauma and Emergency Surgeries As soon as my shift starts, I’m holding a trauma pager that can go off at any minute when someone comes into the emergency department because they’ve been injured or shot. In minutes, you could be opening someone’s chest, trying to manually pump their heart with your hands. I don’t think anyone can get used to that, but I’m sure I’ve unconsciously desensitized a little. You have a job to assess and take care of the patient, so you focus on that instead of what’s happened to them. But I think about it later, when I’m home trying to decompress and go to sleep. When someone’s injuries are severe or they don’t make it, at the end of the day, you can’t help but reflect. That person was someone’s mom, someone’s brother or sister, someone’s someone. But in the moment, you have a job and a mission, and you might be able to make them better, so you don’t think about that.

As a Level I trauma hospital, CedarsSinai is a leader in providing the highest level of care to injured patients throughout Southern California. Once a week, on average, Ruth and Harry Roman Emergency Department trauma teams race to save someone’s life after an act of gun violence or a suicide attempt.

Experts continue to care for patients through intensive care and rehabilitation.

SUMMER 2019 | DISCOVERIES |

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As soon as 39-year-old Amy Fire sits down to take a breath, her 2-yearold son, Phoenix, hops into her lap.

“Mommy, I want a snack,”

he announces. A minute later, her 6-year-old son, Fenris, strides into the room.

“Mommy, can you read me a book?”

No Time for MS

By AMY PATUREL • Photography by RAMIN RAHIMIAN

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L

ike many parents, Fire is used to juggling a few dozen balls simultaneously. The mother of two is also a PhD-level scientist.

“I like to stay busy,” she says, citing the built-in cabinets she fabricated from scratch while she was seven months pregnant with Phoenix and completing her thesis. Her latest project: working alongside her husband, Kaolin, at Grabango, a company that’s developing a checkout system to allow people to walk into a store, grab the items they want, pay and leave—all without stopping at a cashier.

Amid this busyness, Fire is also navigating multiple sclerosis (MS), a degenerative disease that attacks the fatty myelin sheaths that protect nerve cells and allow them to communicate. With MS, the patient’s immune system damages the healthy nerves in the brain and spinal cord. Like a fraying electrical wire, nerve cells with damaged myelin can short-circuit, causing a constellation of troubling symptoms ranging from blurry vision to trouble with balance and speech.

In Fire’s case, MS means she can’t count on her legs to do what they should. When she walks, they often give out. And if her kids play too roughly with her, they might knock her down.

She also suffers from periodic fatigue, numbness in her left hand and occasionally feeling off-balance.

To prevent the neurological disease from progressing, Fire gives herself injections and, when it’s time for her thrice-weekly shot, both boys run into the room to watch. “They think it’s the coolest thing,” she says.

This is the changing face of MS, a disease that once sentenced women and men to wheelchairs and robbed them of their livelihoods, their independence and their chance to have a family.

Scientists still don’t understand what causes the disease or how to definitively stop it from progressing—and many people suffer for years undiagnosed or misdiagnosed. But with advancing technology, refined diagnostic criteria and more than a dozen treatment options, there is hope.

DIAGNOSTIC ODYSSEY

W

omen are two to three times more likely to be diagnosed with MS than men, primarily between the ages of 20 and 50. Some are preparing to start a family or career, while others are in full swing, managing busy work schedules and households.

“Women are more susceptible than men to autoimmune diseases like MS,” says Nancy Sicotte, MD, director of the Multiple Sclerosis Program and the Women’s Guild Distinguished Chair in Neurology. “There are a lot of theories as to why they are disproportionately affected—hormones may play a role—but the bottom line is, we just don’t know yet.”

Fire has the most common and unpredictable form of the disease, called relapsing-remitting MS, where symptoms shift, striking various areas of the body. They can also spontaneously

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disappear (remit) or recur (relapse). Left untreated, relapsingremitting MS can develop into secondary progressive MS, in which patients experience worsening symptoms without periods of remission.

Like many MS patients, Fire suffered for years before doctors delivered a definitive diagnosis. Her symptoms began in 2000 when she was an undergraduate at the University of California, Berkeley. They were minor, almost unnoticeable without the benefit of hindsight. But, by 2011, when she and Kaolin frequently went on 6-mile walks, her legs would often just give out.

“It was like a bunch of wet clothes were on the ground and my legs were kind of stuck in them,” Fire says, “and when I rubbed my legs together, it felt like they were coated in oil.”

During one of their weekly walks, her husband said, “I hope it’s not MS,” recalling an acquaintance with MS whose legs didn’t function well.

When a doctor at UC Berkeley’s student health center referred her to a neurologist, Fire underwent her first MRI, but it was clear. “The doctor said to return if my symptoms didn’t resolve on their own, which they always did, but then they would come back,” Fire says.

Those persistent and vague symptoms led to a frustrating series of misdiagnoses. One doctor said the numbness in her hand was carpal tunnel syndrome and told her to wear a brace. Another said she was suffering from neuropathy and repeatedly tested her for diabetes. None of them mentioned the possibility of MS. “Unfortunately, no single test can diagnose MS,” Sicotte says.

Instead, clinicians rely on a complex mix of clinical symptoms, imaging tests and spinal fluid analyses to make an educated and informed assessment about whether a patient has the condition.

Physicians get it wrong about 15–20% of the time.

That’s one reason Sicotte, chair of the Department of Neurology at Cedars-Sinai and founding director of the Neurology Residency Program, trains residents and practicing neurologists to review MRIs themselves rather than relying on radiologists who may not be well-versed in the signs of MS. She notes that improved diagnostic criteria do no good if physicians don’t know how to apply them.

Lesions to the central nervous system can occur up to 10 times more frequently than a new symptom. So, even if a patient doesn’t notice a new attack, she can accumulate nerve damage while waiting for answers. On an MRI, those lesions show up as bright white spots. “The image lights up like a Christmas tree,” Fire says.

The problem is, other conditions—such as diabetes, hypertension, stroke and even migraines— also produce ominously festive MRIs. Therefore, doctors like Sicotte look for bright spots of a specific size, shape and location.

“MS lesions have a distinctive oval shape, a bit like a football,” Sicotte says. Almost all MS lesions have a vein running through the middle because the immune system’s fighter T cells lock on to small vessels where the blood runs more slowly. From there,

Kaolin and Amy Fire enjoy some relatively quiet time with sons Fenris and Phoenix.

they can break through into the brain or spinal cord and cause an inflammatory attack on myelin that appears as the lesions visible on MRI scans.

CHASING DREAMS

M

ore than a decade after Fire’s first MRI, doctors referred her to a neurologist. “The neurologist reimaged my entire spine and said, ‘It’s textbook MS,’” Fire says.

“After I was diagnosed, I went over the old UC Berkeley records again and I saw the doctor’s note. She suspected MS.” Irritated with the misdiagnoses, Fire was also disappointed with herself. “If I had carried my records through, somebody would have picked up on it sooner,” she says. The same week she was diagnosed, her husband was laid off and, as Fire was driving around a curve in the middle of the desert, she hit a ditch and totaled her car. “It felt like a metaphor for my future,” she says. Her body, like her car, was beyond her control.

Even though the neurologist cautioned against reading about MS online, Fire saw stories about people diagnosed with an aggressive form of the disease who were in wheelchairs at age 29. Nearly every story linked MS with a poor quality of life and early death. “I wondered if having a family was in the cards for us,” she recalls.

Regrettably, when patients like Fire are first diagnosed with MS, they often see outdated information and think their future is being erased. “They have a real fear that the trajectory of their

disease will lead them to a wheelchair,” says Marwa Kaisey, MD, a neurologist and MS specialist in the Department of Neurology at Cedars-Sinai, whose own mother was diagnosed with MS when Kaisey was a teenager. “A neurologic diagnosis is not something anyone expects to happen at that age, and MS is not curable.”

But it doesn’t have to derail patients’ lives. Instead, MS becomes something patients can manage, like diabetes. “Some patients diagnosed today can still have the career and family they planned,” Kaisey adds.

Scientists used to believe pregnancy made MS worse because many women experience a relapse during the postpartum period. But when examined over an entire year, relapse activity is about the same, whether patients become pregnant or not—and relapses tend to decrease during the third trimester. So, instead of telling women they can’t have children, doctors find that an MS diagnosis frequently precipitates family-planning discussions.

That was certainly the case for Fire, whose diagnosis nudged her and her husband to start the family they’d been avoiding talking about for more than a decade. “I was terrified of the medication and admitting my MS was real. Starting a family seemed like a way to put all of that on the back burner since none of the medications for MS are approved for use during pregnancy,” she says.

After Fenris was born, Fire continued working toward her degree. She was determined not to let MS get in the way of her SUMMER 2019 | DISCOVERIES |

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dreams. And since she was nursing Fenris, she stayed off medication postpartum. Her life seemed to be on course. But eight months after Fenris was born, MS threw Fire off her axis again when she woke up with blurry vision.

She went to the optometrist who determined she was suffering from optic neuritis, a condition linked to MS in which damage to the myelin surrounding the optic nerve interferes with the transmission of visual information from eye to brain.

“By the time I left the optometrist’s office, I could see clearly only out of one eye. The other eye could only sense light,” Fire says. “It completely freaked me out.”

She received a standard treatment for patients suffering a relapse: high-dose steroid infusions for three days. “It knocked the relapse down quickly, returning my vision to normal within days, while waiting it out could have taken months,” she says.

Unfortunately, steroids also come with serious long-term drawbacks, putting patients at risk for cataracts and osteoporosis—while doing nothing to halt the progression of MS. Plus, steroids can make life pretty miserable. “I remember not being able to sleep, and my husband remembers me being angry and stressed out,” Fire says.

Add it all together, and the experience nudged her toward another change: disease-modifying therapy.

MS: A BUCKET DIAGNOSIS With advanced imaging technology and revised diagnostic criteria to define MS more broadly, fewer patients are falling through the cracks. The problem is, more people are being misdiagnosed with MS. In a study led by Cedars-Sinai neurologist Marwa Kaisey, MD, 1 out of every 5 or 6 patients who received a firm diagnosis of MS turned out to be suffering from something else. And up to 72% of them had been taking diseasemodifying therapies they didn’t need, sometimes for decades.

These statistics reflect the challenge of correctly spotting MS. Symptoms like intermittent numbness, tingling and fatigue are common in conditions ranging from menopause to diabetes. To complicate matters, brain MRIs for disorders like migraines produce an image that’s eerily similar to a brain MRI of an MS patient.

In Kaisey’s study, migraine was the most common misdiagnosis among patients with MS—with good reason.

Both conditions disproportionately affect young women and both present with similar symptoms, such as numbness and tingling. Other misdiagnoses include cerebral palsy, neuropathy and even anxiety.

“We have to find that sweet spot where we’re identifying people at the onset of disease, but we’re not misdiagnosing people,” says Nancy Sicotte, MD.

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DRILLING DOWN

T

he medical response to an MS diagnosis today is radically different from what physicians could offer a few decades ago.

“If a neurologist thought a patient had MS—a condition with no effective treatment—there wasn’t any urgency to make the diagnosis,” Sicotte says. “In particular, we didn’t want to tell somebody, ‘I think you have MS but I’m not sure,’ which would cause significant stress and might not be accurate.”

By the time Kaisey’s mom was diagnosed in the late 1990s, only three medications were available. Now there are more than 15, including therapeutics that could dramatically alter the course of the disease. All of this means that the way doctors care for people with MS has shifted significantly, and the development of disease-modifying therapies has been lightning fast.

“There’s a lot of hope in what we do,” Kaisey says.

But deciding which therapy to pursue first can be a lifechanging gamble. Until recently, doctors focused exclusively on treatments that target immune T cells, the “effecter” cells that infiltrate the brain and spinal cord and strip the nerves of myelin. Some of these therapies make T cells less inflammatory.

Others block them from getting into the brain and spinal cord.

The newest medicines in this class sequester T cells, locking them up inside the lymph nodes.

The rub: As these therapies become more adept at obliterating T cells, patients become more vulnerable to infection.

“There’s an increased risk of unintended consequences, including a life-threatening brain infection called progressive multifocal leukoencephalopathy, or PML, which is caused by a virus that about half of us carry,” Sicotte says, noting that the virus is harmless in people with normal immune systems.

Recently, scientists uncovered another key player in the attack on patients’ immune systems: B cells. “We think what’s happening is that B cells are presenting bits and pieces of myelin to the T cells and saying, ‘Here, go find this and get rid of it; it’s a foreign invader,’” Sicotte says. The T cells go in search of myelin and, when they find it, they launch their attack.

Enter B-cell depleters. These drugs are not associated with PML because they don’t affect the number of T cells. Instead, they eliminate only the B cells that activate T cells to go after myelin.

In the past, doctors typically started patients on the safest, most time-tested treatments—the oldest T cell-targeting therapies—and, if those treatments didn’t control the disease, they would gradually work up to more effective but riskier options.

The latter class of drugs interferes with the immune system’s standard operating procedure and can generate side effects like repeated infections, and kidney or heart problems.

“Despite the increased risk of side effects, we have seen a complete 180-degree shift where we sometimes start patients on the most effective treatments from the very beginning, including B-cell depleters,” Kaisey says.

Both Sicotte and Kaisey are part of a team of investigators

exploring which form of therapy is best for newly diagnosed patients through a national, multicenter clinical trial called TREAT-MS. The goal of the trial: to determine whether patients would benefit more from early, aggressive therapy, or from ramping up from less intense medications to more aggressive ones if those initial drugs fail.

“We are not just trying to stall disease progression, we’re also trying to predict what their disease process will look like 10, 20, even 40 years down the line,” Kaisey says.

Historically, about half of relapsing-remitting MS patients would develop secondary progressive MS within 10 years.

Emerging research suggests that disease-modifying treatments allay progression—and the effect seems to be even better with the newer generation of therapies.

Homing in on a treatment strategy is as personal as it is complex. Physicians determine a patient’s risk profile and then examine lifestyle factors like travel habits and fear of needles, and medical issues like the presence of other chronic conditions.

Deciding between the options was easy for Fire. She has a low threshold for big risks and wanted to play it safe. She started with Copaxone but, when it turned out she was allergic to the drug, she and Sicotte selected a similar injectable, Rebif.

“The medication does nothing to minimize my symptoms,” Fire says. “I just want the peace of mind of knowing I’m doing everything possible to stall the progression of the disease.”

THE BIG UNKNOWN

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espite her anxiety, Fire shows no signs of slowing down. She and her husband live in Berkeley with their two children. Every six months, she travels to Los Angeles to check in with Sicotte. “It’s like going to see an old friend,” Fire says. “I really feel like she cares about me and she

cares about my kids.”

In addition to taking medication to keep the disease from progressing, Fire plans family menus around local, seasonal vegetables, tries to manage her stress levels by getting help at home and exercises regularly. “Exercise is a wonder drug for any neurological condition, not just MS,” Sicotte says. “You’re going to do better if you’re in good shape.”

But Fire can occasionally dwell in worry despite her treatment and healthy habits. Her relapse in 2014, after Fenris was born, scared her. “I had to face questions like ‘Am I going to be able to chase my kids around the playground? Or is that not for me with this disease?’”

Fire manages the impact of her condition day by day, often finding it tough to distinguish which symptoms are related to disease progression and which are just part of “midlife mommying.” “I sometimes feel especially tired at the end of a day. Is that because of MS or is it because many moms feel depleted when their kids are finally in bed?” Fire muses. “There’s no definitive answer.”

At the same time, she and her husband savor their work together, both in their careers and in raising their family. She even ran a 5K in 2017. “We sometimes struggle to get through the day, just like any other American couple trying to raise kids,” she says. “So I’m not sure having MS makes a difference in our daily existence. My life is pretty great and I’m grateful that modern medicine has come as far as it has with regard to this disease.”

Meanwhile, scientists keep knocking down preconceived notions about what it means to have MS. With the introduction of new and better therapies, MS has transformed from a diagnosis of despair into a manageable condition.

“Now when I diagnose someone, I’m able to say, ‘You likely will be able to live the life you planned. MS is going to be part of your life, but it’s not going to be your whole life,’” Kaisey says.

“That’s a win!”

DEPRESSED WITH MS A multiple sclerosis (MS) diagnosis can be depressing, and not just because of the psychological and emotional fallout of the diagnosis. Unlike other chronic diseases, such as cancer, diabetes or lupus, with MS, a biological basis explains why patients feel depressed.

“Depression is part of the disease process,” Nancy Sicotte, MD, explains.

“Changes in the brain that are associated with MS disease activity impact structures in the brain that are important for mood.”

That assault on the brain means even

optimistic patients can get hit with the sense that their world is falling apart and may not be worth patching back together.

In fact, at least 50% of people with MS will experience depression at some point during the course of their disease.

But there is some good news: Preliminary research suggests those brain changes may be reversible with appropriate treatment.

“We usually recommend a combination of medication and therapy,” Cedars-Sinai neurologist Marwa Kaisey, MD, says. Cedars-Sinai is one of three

sites in the United States recruiting patients to participate in a study testing whether online cognitive behavioral therapy can improve symptoms of depression among MS patients.

“An online platform is a nice idea because people with MS sometimes have mobility issues or they’re working, raising a family or just busy living life, and it’s hard for them to keep a weekly appointment,” Kaisey says.

The course has already been validated among people with depression who do not have MS.

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A RACE AGAINST

A PREGNANCY DISORDER CALLED PREECLAMPSIA REMAINS A LEADING CAUSE OF MATERNAL MORTALITY. IT CAN STRIKE LIKE LIGHTNING, ENDANGERING BOTH MOTHER AND CHILD. A DREAM TEAM OF INVESTIGATORS AT CEDARS-SINAI IS DETERMINED TO RENDER THIS MYSTERIOUS DISEASE A RELIC OF THE PAST.

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ady Sybil of Downton Abbey, a rebel who married the family chauffeur, had just given birth to a healthy daughter when the plot of the popular British television series took a shocking twist. The beloved character suddenly fell into convulsions and died.

She suffered from a severe form of preeclampsia, a pregnancy disorder that begins with high blood pressure and can trigger a cascade of other complications—turning what is supposed to be one of life’s most joyful milestones into a devastating health crisis.

By SHERRY ANGEL Illustration by CHRISTINA CHUNG

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Preeclampsia means “before the lightning” in Greek. As Lady Sybil’s fate illustrates, life-threatening seizures can strike with lightning speed.

Set in the early 1900s, Downton Abbey made headlines on both sides of the pond with this heart-rending episode from 2013. It also called attention to the disturbing fact that preeclampsia can be as dangerous today as it was a century ago. In fact, hypertensive disorders of pregnancy like preeclampsia affect nearly 400,000 women in the U.S. each year.

The only cure for preeclampsia is delivery of the baby—and the placenta, where the disease process begins. But what helps the mother could harm the baby. Preeclampsia is a major cause of preterm birth that can put infants in intensive care for months and lead to long-term health and developmental problems. The condition also is responsible for as many as 500,000 infant deaths and 76,000 maternal deaths across the globe annually.

The United States has the dubious distinction of preeclampsia rates that are three to four times higher than that of other developed countries. And African American women face even higher risk: They are three to five times more likely than white women in the U.S. to suffer from the condition.

But change is coming. A dream team of Cedars-Sinai physicians is aggressively pursuing solutions.

THE DREAM TEAM “Preeclampsia has been talked about for hundreds of years, yet it remains a mystery,” says Sarah J. Kilpatrick, MD, PhD, a nationally renowned expert in maternal-fetal medicine and women’s health, and chair of the Cedars-Sinai Department of Obstetrics

ANOTHER PATH TO PROGRESS IN FIGHTING PREECLAMPSIA Sometimes the immune system that is supposed to protect us from disease goes haywire and triggers health problems instead of fighting them off. Richard M. Burwick, MD, assistant professor in the Cedars-Sinai Department of Obstetrics and Gynecology, believes this is what happens with preeclampsia.

As he explains, proteins that help regulate the immune system become overactive during pregnancy. “The body starts reacting against the pregnancy by activating these proteins as if there’s a bacterial infection that it needs to fight,” he says.

He’s preparing to launch a preeclampsia clinical trial this summer to explore the safety and effectiveness of a drug that inhibits these proteins and has been approved by the FDA to treat certain blood disorders. He believes this could be an effective way to prolong pregnancy for preeclampsia patients and to prevent severe side effects such as organ damage and destruction of red blood cells and platelets.

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and Gynecology.

A physician-scientist who has treated more than 1,000 women for preeclampsia, she says each case requires vigilance because no one knows what course this unpredictable disorder will take. “We don’t know why some patients get it and others don’t, or who will develop severe symptoms,” explains Kilpatrick, the Helping Hand of Los Angeles Chair in Obstetrics and Gynecology.

She is now working closely with two leading preeclampsia investigators: Ravi Thadhani, MD, MPH, and Ananth Karumanchi, MD. Both are kidney specialists who came to Cedars-Sinai in 2017 from different Harvard Medical School training hospitals in Boston, where they had collaborated for nearly two decades.

Thadhani is vice dean of Research and Graduate Research Education and chair of Biomedical Sciences at Cedars-Sinai. Karumanchi is the Medallion Chair in Vascular Biology and director of Nephrology. In recent European studies, they jointly developed a test for early detection of preeclampsia as well as an experimental therapy. They see Cedars-Sinai as the ideal place to validate and build on the promising results.

“This institution fosters a drive to make a difference in human lives,” Thadhani says. “We have the support we need to push this work over the finish line.”

Thadhani and Karumanchi say they are excited to have the opportunity to collaborate with Kilpatrick and others at CedarsSinai who are studying links between pregnancy disorders and heart disease later in life. But their first priority is preeclampsia.

The pair joined forces with Kilpatrick to lead a national, 12-site study that aims to win Food and Drug Administration (FDA) approval for a reliable preeclampsia diagnostic test. The study, launched in April, focuses on a critical question: Which patients with preeclampsia are at highest risk of developing severe symptoms that could quickly become life-threatening?

The test could give doctors vital information to guide medical decisions, such as which patients need treatment to prevent seizures, who needs to remain hospitalized before their due date and how long it’s safe to delay delivery. The next step will be to hone a treatment approach that Thadhani and Karumanchi began working on years ago in Boston. They are determined to accelerate progress in a field that has too long been neglected.

CATCH-22 Women with preeclampsia may be hospitalized for weeks so they can be closely monitored for signs of severe disease such as kidney failure, fluid in the lungs and liver damage. During this time, physicians and patients are trapped in a catch-22, trying to manage the health of the woman while protecting her unborn child.

“All we can do is monitor the mother closely, manage symptoms as they arise and try to prolong the pregnancy as long as possible.

It’s a delicate balancing act,” Kilpatrick says.

This balancing act can put mothers-to-be on an emotional roller coaster. Melissa Salama, a Los Angeles mother of three, has

Melissa Salama and baby Ruby are both healthy today despite preeclampisa that led to preterm delivery.

Rachael Porter

been there—twice.

The first time was seven years ago, when she gave birth to her first child in New York at age 34. She developed high blood pressure late in the pregnancy, after experiencing uncomfortable swelling and extreme fatigue for weeks. Her daughter, Molly, was born two-and-a-half weeks early. Both mother and child came through with no health problems, although it took a couple of months for Salama’s blood pressure to get back to normal.

Her second child, Ben, now 4 years old, was born a week past his due date at Cedars-Sinai. Salama’s blood pressure was a bit high at the end so she finished the pregnancy on bedrest as a precaution, but preeclampsia did not become a problem.

Then came Ruby. Salama had the same disturbing symptoms as in her first pregnancy, but they were worse this time and started earlier. “I felt so rundown and had an incredibly difficult time focusing on anything. I was anxious about making it to the end of the pregnancy. I knew it could get very bad,” Salama recalls.

Her doctor, Karyn Morse Solky, MD, clinical chief of the CedarsSinai Department of Obstetrics and Gynecology, advised her to come to the hospital on a Friday morning last December because her blood pressure had been consistently high and her blood platelet count was falling, putting her at risk for internal bleeding. She was treated with medication for hypertension and magnesium sulfate to prevent seizures. It was a month before her due date.

“My husband and I were very worried that it was too early and there could be lasting effects on our baby,” Salama says. “We were also scared about whether I would be OK. And I was worried about my two kids at home. I needed to get back to them.”

PUSH FOR CHANGE One reason mothers like Salama find themselves in such an agonizing position is because pregnancy has often not kept pace as a focus of medical research. Fear of harming the fetus is a formi-

dable barrier to developing scientific evidence to guide clinical care when mothers-to-be develop complications.

Kilpatrick explains: “Most medications we use during pregnancy are classified as Category C by the FDA, which means we don’t have proof they’re safe during pregnancy because they haven’t been studied in humans—yet the potential benefits may outweigh the risks. I almost always recommend taking the medication for conditions such as hypertension, depression or Crohn’s disease because it’s riskier for the mom to stop it, and we know from experience that the risk to the fetus is small.”

Thadhani says he doesn’t know of any pharmaceutical or biotech firm that has made it their mission to develop treatments for preeclampsia, and women’s health issues in general are not a priority. “We’ve pitched our research to more than 30 companies without success,” he says. “One problem could be that 99.9% of the people making the decisions are men.”

But the biggest obstacle to finding industry partners for this research is most likely a ghost from the past.

In the late 1950s, the drug thalidomide was prescribed to relieve nausea and morning sickness in pregnancy. It resulted in a worldwide tragedy: Thousands were born with severe birth defects such as malformed limbs—only 40% survived. “It is still fresh in people’s minds. It still keeps companies from supporting pregnancy studies that could open them up to a lawsuit,” Karumanchi says.

He notes another deterrent to obtaining industry support: The biology of preeclampsia has not been understood well enough to identify clear targets for drug development. He and Thadhani have made major contributions to advancing this knowledge, while pursuing a path to treatment that would not put the fetus at risk.

MAKING THE IMPOSSIBLE POSSIBLE After years of working at different hospitals five miles apart, Thadhani and Karumanchi no longer have to schedule a time and place to meet. “This is the first time we’ve worked under the same roof,” Thadhani says. “It’s great to be able to butt heads with each other in the same lab every day.”

The two investigators feed off each other’s creative energy. While Karumanchi’s demeanor is casual and laid-back, Thadhani has perfect posture and a polished manner. He stands at a whiteboard in his office and writes key points as the two discuss their work.

But appearances can be deceiving. Karumanchi respectfully describes his longtime research partner as “a bit on the edge.”

“You have to be a little crazy when you’re trying to do what’s never been done before,” he says. “Ravi thinks outside the box. He believes nothing is impossible.”

Thadhani appreciates the way Karumanchi helps him “stay grounded.” He adds: “I’ll see a problem in the clinic and he’ll help explain the biology. This is the yin and yang of our partnership.”

In Boston, they often brainstormed at a Borders bookstore about halfway between Thadhani’s lab at Massachusetts General SUMMER 2019 | DISCOVERIES |

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Hospital and Karumanchi’s lab at Beth Israel Deaconess Medical Center. One afternoon in 2008, they braved a blizzard to meet there.

They stayed for hours. And it wasn’t because they were waiting out the storm. They vowed not to leave until they figured out an approach to treating preeclampsia that would help the mother without harming the baby. It turned out to be one of the most productive meetings of their careers.

A LITTLE BIT OF LUCK As an expert in vascular biology, Karumanchi became fascinated years ago with growing evidence that preeclampsia damages the cells that form the lining of blood vessels. He figured the cause had to be one or more of the proteins released into the mother’s blood vessel system by the placenta. But which one?

Finding the culprit could have been a daunting, needle-in-ahaystack undertaking. But he got lucky. He was able to use new technology to examine the entire genome of the placenta in a single snapshot, rather than looking at one protein at a time to determine whether it was elevated in preeclampsia patients.

“I was asking the right question at the right time,” he says. “This technology had just come out. Without it, I might have spent 50 years trying to do this.”

The “brightest signal” came from a “bad” protein called soluble

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fms-like tyrosine kinase 1 (sFlt-1). Also significant was a “good” protein essential to healthy blood vessels: placental growth factor (PIGF). Karumanchi had a hunch that preeclampsia was triggered when the “bad guys” outnumbered the “good guys,” causing blood vessels to constrict instead of relaxing and opening up to support blood flow for a healthy pregnancy.

While Karumanchi was working on this basic biological science, Thadhani was studying high blood pressure in women and caring for preeclampsia patients in the clinic. He found it frustrating not to be able to do more for them. When he heard about Karumanchi’s results, he knocked on his door. The two launched a study using 10,000 tissue samples Thadhani had collected from pregnant women in Boston to validate Karumanchi’s theory.

This led them to the diagnostic tool that is now the focus of a clinical trial at Cedars-Sinai. The study seeks to identify a ratio between the “bad” and “good” proteins that would help identify patients most likely to develop severe symptoms of preeclampsia.

Once they confirmed the role of the “bad” sFlt-1 protein in preeclampsia, they knew they had a critical building block for a treatment as well as a diagnostic test. Anyone who observed them on that stormy day in the bookstore in Boston might have thought they were arguing. “We sat there for hours trying to figure out the best approach. It was a cognitive wrestling match,” Thadhani says.

Their expertise as kidney specialists led them to an answer.

Rachael Porter

Drs. Karumanchi, Kilpatrick and Thadhani have joined forces to seek FDA approval for a reliable preelampsia diagnostic test.

What helps the mother could harm the baby. “It’s a delicate balancing act.”

—Sarah Kilpatrick, MD, PhD

Salama says. The only issue that continued after they got home was that Ruby was too weak to nurse. Salama reluctantly stopped breastfeeding far earlier than she had planned.

Overall, dealing with preeclampsia was “an incredibly stressful experience for the whole family,” she says.

“Dr. Solky was very understanding about how nervous we were,” Salama says. “She acted quickly, and we’re thankful it was an excellent outcome. Ruby is healthy and I feel good now.”

‘DON’T GIVE UP’ “Our predecessors in nephrology realized that, rather than taking out whole blood, we can tinker with it to take out what’s bad and leave in what’s good,” Thadhani says. “Nephrologists have been pioneers in selective removal strategies.”

A light bulb went on: Instead of developing a drug targeting sFLt-1 that might cross the placenta and damage the fetus, why not remove the offending protein from the mother’s bloodstream?

Three years later, Thadhani and Karumanchi launched their first treatment study in Europe. Using a process similar to kidney dialysis, they modified existing technology to develop a device that removes blood through a catheter, runs it through a machine that eliminates sFLt-1 and then returns the blood to the mother.

Thadhani says they’ve been able to extend pregnancy for about two weeks, a significant period for development of the fetus. The findings of their first pilot study on this potential treatment method were published in 2011 in Circulation. A follow-up study published in 2016 by the Journal of the American Society of Nephrology confirmed the initial findings and set the stage for the next step—validating these results in larger U.S. studies.

In 2006, a lengthy article by Jerome Groopman in The New Yorker featured Karumanchi’s effort to identify the proteins released from the placenta that trigger preeclampsia. Karumanchi says the article helped increase awareness of this disease at a time when it was much less understood than it is today.

However, he adds, “The most important thing that came out of the article was the many emails I received from patients.”

He will never forget the gist of these messages: “Keep going.

Please don’t give up.”

Karumanchi and Thadhani have no intention of giving up. They are committed to continuing their work with Kilpatrick and other research partners until they change the trajectory of this disease.

Meanwhile, Kilpatrick continues to deliver an important message to patients: “They may feel they did something to cause this, so I always tell them, ‘It’s not your fault.’ There’s no reason for a woman to feel guilty about getting this disease. It’s just bad luck.”

“This disease keeps you very humble,” Karumanchi says. “Women’s lives are at stake. We have to change that.”

A MOTHER’S HOPE FOR THE FUTURE

BY THE NUMBERS

When Salama was admitted to Cedars-Sinai a month before Ruby’s due date, she knew every day would make a difference in her baby’s health. Fortunately, she was already in a safer zone at 36 weeks than many other mothers-to-be in her situation.

Kilpatrick says standard practice is to deliver at 34 weeks when the mother’s symptoms are severe, because “babies do well after this point.” Decisions get tougher when severe symptoms of preeclampsia appear earlier in the pregnancy.

In Salama’s case, her symptoms were getting worse and time was short. But she was relieved to learn that she would receive a steroid injection to help the baby’s lungs develop, and they would wait 48 hours to induce labor. While her husband, Evan, alternated between supporting her at the hospital and reassuring the kids at home, she did deep-breathing exercises to calm herself.

Five days after Salama entered the hospital, Ruby was born. She weighed 4 pounds, 15 ounces, and was stable enough to be held by her mom for two hours before she began a five-day stay in the NICU. Ruby didn’t have severe problems, but needed to “mature a bit,”

Hypertensive disorders of pregnancy impact an estimated 5–8% of all pregnant women—including 400,000 in the U.S. annually.

Preeclampsia causes as many as 76,000 maternal deaths and 500,000 infant deaths across the globe each year.

Preeclampsia typically occurs after 20 weeks of pregnancy, in the late second or third trimester, and postpartum eclampsia may occur up to six weeks after delivery.

At least a third of deliveries involving mothers with preeclampsia occur before babies come to term at 37 weeks.

About 25% of preeclampsia cases involve severe symptoms.

The average amount of time between diagnosis of preeclampsia and delivery of the baby is seven days.

Preeclampsia is on the rise, with incidence in the U.S. increasing 25% over the last two decades—another puzzle for investigators to solve.

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NOT L O S T

IN TRANSLATION

COMMUNITIES MOST AT RISK FOR CANCER ARE AMONG THOSE RECEIVING THE LEAST MEDICAL ATTENTION. CEDARS-SINAI INVESTIGATORS ARE USING A CULTURALLY TAILORED APPROACH TO REDUCE DISPARITIES IN CANCER PREVENTION AND TREATMENT—FROM KOREATOWN TO LGBTQ POPULATIONS.

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ntil her Medicare coverage kicked in five years ago, Myong Shim Lee visited her family doctor only when she was really sick. She lacked health insurance for most of her adult life, so she never considered mammograms, colonoscopies or gynecological exams. Her doctor, who also treated her extended family, did not discuss preventive care and never mentioned the possibility of cancer. Basically, she says, she had no clue.

“The only time people in my community talk about cancer is if a friend has a pain and the doctor finds something wrong,” says Lee, 70, who emigrated from South Korea to Los Angeles in 1977. Health information trickles down secondhand, she says, if the friend survives the disease. “People gossip about someone having cancer, but it’s very hard to get correct information before an actual diagnosis.”

By DIANE WEDNER Photography by MISHA GRAVENOR

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Myong Shim Lee has become an advocate for cancer prevention, encouraging peers in her Korean American community to seek out screening tests.

That culturally ingrained health behavior is common in many underserved populations—groups defined by race, ethnicity and socioeconomic status. Its toll is high. Fear and embarrassment as well as a lack of financial resources, health insurance, information and transportation act as barriers to accessing care. These populations exhibit higher rates of cancer, chronic illnesses and deaths compared with their peers in other groups, says Robert Haile, DrPH, MPH, the Cedars-Sinai Chair in Cancer Population Health Sciences. The Research Center for Health Equity, which he directs, is tackling the problem in Southern California communities, neighborhood clinics and Cedars-Sinai’s laboratories.

HEALTHCARE JUSTICE Narrowing the health disparities gap has taken on particular urgency as the U.S. population has become more diverse. In 2016, 4 in 10 people living in the U.S. were people of color. That number will jump to more than half the population by 2050, according to the U.S. Census Bureau. The underserved make up a disproportionate share of uninsured people, highlighting the urgency for action.

“There is a tremendous need to bring current, accurate information about health risks and prevention to underserved communities,” says Haile, a national leader in population studies. “Once we determine why certain groups don’t get screened for colon and other cancers, for example, we can be smart about how to address that problem.”

“That people lack information, understanding and access to cancer care is deeply unjust,” says Zul Surani, associate director of the research center. He lost his mother to cancer, prompting his career commitment to reach those most in need of cancer information.

“For me, correcting those inequities is a matter of justice.”

Closing the health-disparity gap also has economic benefits.

The Kaiser Family Foundation recently reported that healthcare inequality accounts for about $93 billion annually in excess medical care costs and $42 billion in lost productivity in addition to the economic losses due to premature deaths.

Cedars-Sinai’s research center already has sprung into action in Koreatown, Pico-Westlake, and other communities in Los Angeles County and across Southern California. Surani and his outreach team hold educational health workshops for neighborhood groups in churches and community centers. The team also arranges cancer screenings at free clinics.

GOSPEL OF MEDICINE The timing of the research center’s efforts comes not a minute too soon for Lee and her husband, Ki Tae Lee, 82. Concerned about their health—particularly about cancer, as they age and as friends confront the disease—the pair is eager to gather all the accurate health information they can. And then share it.

“We spent most of our lives not talking about cancer with anyone,” says Myong Shim Lee, now an information warrior. “My

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primary care doctor always says, ‘You’re okay, you’re okay,’ rather than discussing test results and answering my questions. I wanted answers.”

So she got them. In November, the Lees headed to Los Angeles Onnuri Church in Koreatown where, Myong Shim Lee says, the research center’s cancer-education workshop changed her life.

She and her husband assiduously took notes as Dong Hee Kim, a research center community outreach coordinator, talked frankly— in Korean—about cancer risks, prevention, treatments, screenings and clinical trial enrollment. The attendees also got one-on-one advice about health insurance.

The Lees now get regular cancer screenings, and Myong Shim Lee preaches the gospel of cancer prevention to others in her senior social groups. She also continues to educate herself about the benefits of nutritious foods and exercise.

Once her health enthusiast’s engine was revved, she and her husband decided to enroll in a three-month program to get certified as home healthcare providers, from which they graduated in May. “In my whole life, this is the most important decision I’ve made:

CANCER PREVENTION IN K-TOWN Los Angeles County is home to the nation’s largest Korean and Korean American population. This growing community faces distinctive medical challenges—from increased cancer rates to lower-than-average screening levels. The new Research Center for Health Equity at Cedars-Sinai aims to close the healthcare gap for this and other underserved groups.

THE NEED

RISK FACTORS

Several types of cancer have become more prevalent among the U.S. Korean population.

Between the 1990s and 2005, prostate cancer, breast cancer and colorectal cancer all increased sharply in this group.

Disparities among Koreans have become more pronounced, especially among those who are foreign-born, of lower socioeconomic status and living in areas with high ethnic concentration. Some 67% of the 226,000 Koreans in Los Angeles County are foreign-born.

Koreans have the highest rate of stomach cancer of any ethnic group in the U.S. and are experiencing rising liver cancer rates. These disproportions are greater among first-generation immigrants.

Health behaviors linked to increased cancer risk among the U.S. Korean population include: Mammography rates that lag behind that of the general population Lower colorectal cancer screening rates Smoking cigarettes

•

• •

health information, she says. That’s why she ignored a lump in her breast for months, until finally asking a friend to examine it.

“She screamed at me to go to the doctor,” says Terry, now 59.

Still, one biopsy, two surgeries, several rounds of chemotherapy and radiation, and one attempted breast reconstruction later, Terry was determined to forget her cancer. She skipped follow-up appointments, steered clear of support groups, which made her feel uncomfortable, and learned only minimally about cancer. “If I had pain,” she says, “I took a Tylenol.”

Then, 12 years later, in 2016, struggling to breathe during a short walk, Terry checked into a local emergency room. Following tests, the doctor revealed that the cancer had returned, at stage 4, igniting worry and anguish all over again. Additional tests showed the cancer had spread to her chest, esophagus, several lymph nodes in her underarm and other sites.

Like Myong Shim Lee, Terry visited doctors only when she was ill. But after her second breast cancer diagnosis, Terry joined a support group. At the suggestion of one her friends there, she attended a joint Research Center for Health Equity/Susan G. Komen educational event at Cedars-Sinai in January.

“I immediately felt more comfortable with my own situation after hearing the Cedars-Sinai experts talk about helping myself with a good diet, exercise and supportive care, which I’m doing now,” Terry says. “It gave me a good feeling to talk to other women with breast cancer. We laughed a lot and shared information.”

Myong Shim Lee and husband Ki Tae Lee pause outside a flower shop near Los Angeles Onnuri Church in Koreatown, where a Cedars-Sinai cancer-education workshop gave them a new perspective on healthcare.

to learn about wellbeing, aging well and even dying well,” she says.

The Koreatown seminars were arranged by Surani along with Jeong Yup Lee, senior pastor of Onnuri Church. Pastor Lee’s father, who died of lung cancer in 1995, wasn’t screened for it, nor did he talk about the risk of lung cancer with his family, despite a lifelong smoking habit, the pastor says.

Now in his Sunday sermons, Pastor Lee talks openly about the reasons for his father’s late-stage diagnosis and emphasizes a holistic approach to medicine. He tells congregants that both their physical and spiritual wellbeing are necessary to maintain good health. “The church looks to restore a person’s heart and soul, while the medical center looks to restore the person’s physical needs,” he says. “When we collaborate with Cedars-Sinai, we make something better than what we can do individually.”

EDUCATION AND EMPOWERMENT Doris Terry regrets the information vacuum that surrounded her before her breast cancer diagnosis 15 years ago. To the busy, single, working parent, regular physical exams and health screenings meant time away from her kids and her job as a teacher’s aide.

Women in her African American community rarely seek or share

A PRECISE PATH FORWARD Surani says that his team’s mission is to share reliable, culturally tailored information about cancer so participants “can feel they’re in control of their futures and their health.”

In December, the team arranged for Latinas to receive free breast cancer screenings at Clínica Romero in Downtown Los Angeles. In addition to its work with L.A. County’s Korean, Filipino, Latino and African American populations, the research center also plans to partner with the Los Angeles LGBTQ community, “which is deeply underserved,” Haile says.

The team analyzes environmental, cultural and genetic factors to understand disparities in cancer rates. For example, it is conducting scientific studies to find out why the incidence of liver cancer is increasing sharply in the Latino population and breast cancer rates are climbing significantly among Korean American women.

To detect early-stage colorectal and other cancers, they are also working on blood-based or “liquid” biomarkers that don’t rely on invasive procedures. The biomarkers may be useful for monitoring cancer recurrence and patient response to therapies. And the team is developing technologies to reach more people in multiple cultural settings and in a number of languages.

As for Myong Shim Lee, she remains dedicated to educating her peers. “My kids are grown, and I don’t have to fight with them anymore!” she jokes, and then turns serious. “I just want to fight cancer.”

SUMMER 2019 | DISCOVERIES |

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Schedule an appointment now at cedars-sinai.org/donateblood or call 310-423-5346.

Faculty News Summer 2019

Richard N. Bergman, PhD, was named to Clarivate Analytics’ 2018 list of Highly Cited Researchers. The citation analysis identifies influential researchers as determined by their peers around the globe and by records that position them in the top 1% of citations for their field during the year.

Bergman is the Alfred Jay Firestein Chair in Diabetes Research.

Neurosurgery residents Drs. Lindsey Ross, Julie Chan and Angelique Do

Women on the Verge Three female residents forge futures in the historically male-dominated specialty of neurosurgery.

Rachael Porter

By STEPHANIE STEPHENS

Even after decades of progress, women still only account for about 17% of neurosurgery residents in accredited programs nationwide. As recently as 2018, the Journal of Neurosurgery lamented that the goal of gender parity in the field seems “remote.”

But not at Cedars-Sinai, where the number of female residents in neurosurgery recently reached an all-time high. Out of a total number of 1,424 female residents nationwide, three are being trained at Cedars-Sinai: Julie Chan, MD, PhD, Angelique

Do, MD, and Lindsey Ross, MD. While this number—which keeps rising—may seem small, these women’s contributions in operating rooms, to patients and even in the foreign countries where they volunteer are immense.

“They are among the best and the brightest attracted to the field,” says Keith Black, MD, chair of the Department of Neurosurgery, director of the Maxine Dunitz Neurosurgical Institute, and the (continued on page 43)

Jonathan Braun, MD, PhD, a pathologist and pioneering researcher in inflammatory bowel disease (IBD), has joined the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute as director of Enterprise Operations. He is a member of the Scientific Advisory Board for the International Early Onset Pediatric IBD Cohort Study, and chair of the Scientific Advisory Board for the Milieu Intérieur Consortium of Institut Pasteur in Paris. Braun previously spent three decades at the David Geffen School of Medicine at UCLA. Susan Cheng, MD, MPH, MMsc, has been named the Erika J. Glazer Chair in Women’s Cardiovascular Health and Population Science.

Cheng, who joined the Smidt Heart Institute in 2018 as director of

SUMMER 2019 | DISCOVERIES |

41

Faculty News

Cardiovascular Population Sciences in the Barbra Streisand Women’s Heart Center and as director of Public Health Research, is a cardiologist, echocardiographer and clinician-scientist who leads research aimed at uncovering the drivers of cardiovascular aging in women and men.

Sumeet Chugh, MD, received the 2019 Douglas P. Zipes Lectureship Award from the Heart Rhythm Society. The honor is bestowed annually to a scientist or clinician who has made a significant and unique contribution to the field of cardiac electrophysiology. Chugh is the Pauline and Harold Price Chair in Cardiac Electrophysiology Research.

Timothy Daskivich, MD, received the American Urological Association’s Rising Stars in Urology Research Award, which is presented to two junior investigators each year and includes a grant of up to five years of supplemental salary support to encourage career development in biomedical, behavioral and patient-oriented research.

Neal S. Elattrache, MD, was installed as the 47th president of the American Orthopaedic Society for Sports Medicine in July 2018. He is head team physician

42

for the Los Angeles Dodgers and Los Angeles Rams, and an orthopaedic consultant to the Los Angeles Angels, Los Angeles Clippers, Los Angeles Kings and Anaheim Ducks.

Robert A. Figlin, MD, was named 2018 Educator of the Year by Physicians’ Education Resource. The award highlights the accomplishments of oncology leaders and honors their efforts to advance the field through innovative and collaborative education. Figlin is the Steven Spielberg Family Chair in Hematology-Oncology.

James D. Grant, MD, MBA, has joined Cedars-Sinai as chair of the Department of Anesthesiology and physician-executive in Perioperative Services.

He was previously chief of the Department of Anesthesiology at Beaumont Hospital in Royal Oak, Michigan, and professor and chair of Anesthesiology at the Oakland University William Beaumont School of Medicine. In 2018, Grant was elected as the 100th president of the American Society of Anesthesiologists.

Irene Kim, MD, has been promoted to co-director of the Comprehensive Transplant Center. Over the past six years since she joined Cedars-Sinai from Stanford, she has assumed a growing

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portfolio of responsibilities, including leading the Paired Kidney Exchange Program for four years and directing the Abdominal Transplant Surgery Fellowship program for the past three years.

Under her leadership, national interest in the training program has grown significantly. In January 2018, she was appointed surgical director of the Kidney Transplant Program.

Asher Kimchi, MD, received the Lifetime Achievement Award in Cardiovascular Science, Medicine and Surgery from the International Academy of Cardiovascular Sciences, an organization he founded that promotes global sharing of research and education in heart health.

Andrew Klein, MD, MBA, began his term as the 2019 president of the International College of Surgeons, U.S. Section, on Jan. 1. One of his priorities will be to help underserved communities through the organization’s global outreach efforts. Klein is the Esther and Mark Schulman Chair in Surgery and Transplantation Medicine.

Jon Kobashigawa, MD, received the 2018 Paul I. Terasaki Clinical Science Award from the American Society for Histocompatibility and Immunogenetics. The

award honors an individual, group or institution that has made significant contributions to the fields of clinical transplantation, histocompatibility and immunogenetics.

Kobashigawa is the DSL/Thomas D. Gordon Chair in Heart Transplantation Medicine.

Milton Little, MD, was one of three orthopaedic surgeons to win the 2018 Orthopaedic Research and Education Foundation’s Young Investigator Award from the Western Orthopaedic Association. The award honors assistant professors and clinical instructors for their efforts to advance the science of orthopaedic surgery through research and mentorship. Little was recognized for his paper on using 3D virtual reality for pain control in orthopaedic patients.

Patrick D. Lyden, MD, received the American Stroke Association’s 2019 William M. Feinberg Award for Excellence in Clinical Stroke to recognize his contributions to stroke research. He is the Carmen and Louis Warschaw Chair in Neurology.

David R. Marshall, JD, DNP, RN, has been appointed senior vice president and chief nursing executive. Most recently, he served as the system chief nursing and

patient care services executive for the University of Texas Medical Branch at Galveston (UTMB Health), where he worked in nursing roles for 36 years. He holds National Healthcare Disaster certification and was instrumental in leading UTMB Health and the Gulf Coast region back from the devastation of 2008’s Hurricane Ike. His many leadership roles include a 2017 appointment to a four-year term on the American Nurses Credentialing Center’s Commission on Magnet Recognition Program.

Marshall earned a doctor of nursing practice degree from Texas Tech University Health Sciences Center School of Nursing, and a law degree from South Texas College of Law Houston. Marshall succeeds Linda Burnes Bolton, DrPh, RN, FAAN, who is transitioning into the new role of chief health equity officer.

Pamela Roberts, PhD, received the Distinguished OT Program Alumni Award from Washington University School of Medicine’s Program of Occupational Therapy. The award honored her for her work in shaping rehabilitation services, policies and practices in healthcare systems, and for her dedication to providing high-quality, data-driven services.

(continued from page 41) Ruth and Lawrence Harvey Chair in Neuroscience.

“If we didn’t recruit women into our program, we’d be missing half of the talent. My colleagues across the country see a similar trend.” It’s a trend that Cedars-Sinai continues to foster.

Meet the Residents Julie Chan, MD, PhD

Her father’s death from a traumatic brain injury sparked Chan’s “passion for studying neurosciences in hopes of discovering new ways to treat traumatic brain and spinal cord injury and prevent others from suffering his fate,” she says.

Chan believes that neurosurgery’s challenges are similar whether the doctor is male or female. “I find the central nervous system fascinating: It is the one organ system whose inner workings we know the least about, yet it is truly integral to who we are as individuals and can’t be artificially replaced.”

Her dedication was quickly spotted by Tiffany Perry, MD, assistant professor of Neurosurgery. “Her patients love her, even when she wakes them up early,” she says.

“I see a lot of me in Dr. Chan—she has nonstop energy.”

Chan thinks it’s remarkable that she gets to have such a visible impact on human life. “It’s all about the patients and their families,” she says. No matter how challenging the day or week has been, she sees those moments of connection as the greatest gifts.

Angelique Do, MD

When Do contemplated studying neurosurgery, she recognized its “boys’ club” reputation and the time commitment required but determined she wouldn’t be happy doing anything else.

She says that being a woman probably contributes to the empathy she brings to

patient interactions.

“Women do pay particular attention to details, like those little hints patients give you when they talk to you,” Do notes. “We are usually sensitive to important emotional needs, and sympathetic with patients. I remember a patient telling me during my morning rounds, ‘You’re always smiling at 4 a.m. You must really love your job.’ And I do.”

As Perry mentors Do and her fellow residents, she regards them as full-fledged colleagues rather than just as trainees. For example, Perry collaborated with Do on a paper about what she calls “an interesting but rare spinal cord tumor.”

Like her colleagues, Do has earned her status in Perry’s eyes. “If Dr. Do says she’ll do something, you know it will be done in a timely manner because she’s passionate about her work,” Perry says. “She’s also trustworthy, honest and has exceptional follow-through skills.”

Do is well-aware that in some professional situations, empathetic traits such as caring and kindness must take a back seat to decisiveness and authority, lest she be labeled in a manner a male might not.

“When it’s stressful, and there are lots of things coming at you, you may say something in an irritated kind of way, like anyone would, and be perceived as ‘difficult’,” she says. Although she says she’s never been treated differently than her male colleagues, she remains vigilant about her self-expression. “I just remember to check myself.”

Lindsey Ross, MD, Chief Resident

Arriving at Cedars-Sinai in her early 20s as a Pauletta and Denzel Washington Family Gifted Scholar in Neuroscience inspired Ross to pursue the field of neurosurgery.

“When we created the program, we hoped it would attract and retain talented doctors,” Pauletta Washington says. “It is now instrumental and successful in

identifying women such as Dr. Ross. I’m happy to know she and other women residents are shattering the glass ceiling.”

Ross had considered surgical oncology or even a career in health policy before she found her home at Cedars-Sinai.

“That summer, one of my good friends was struck by a vehicle and suffered from traumatic brain injury and broken cervical spine,” she says. “Daily, I woke up early to shadow Dr. Black, and in the evening sat in the intensive care unit with my friend and his family. When something like that happens in life, it’s like you’re being called in a certain direction.”

Ross noticed few women in neurosurgery. “Then Dr. Black said, ‘This is something you can do,’ and it changed my career outlook,” she says.

“With Dr. Ross, I see a great daughter, mom, humanitarian and neurosurgeon,” says Perry, who performed spine surgeries—accomplished without the aid of imaging or routine instruments—alongside Ross on a medical mission in Uganda earlier this year. “It’s been beautiful to watch her grow and transition to being so balanced in all her roles.”

Ross says other female physician leaders have modeled polished professionalism. “Women in this specialty have to be very dedicated but also prepared when a patient asks, ‘Are you here to clean the room?’” she says. “They don’t do it with mal intent, and fortunately the culture is changing.”

That change has unwavering support from both Black and Perry. “These women distinguish themselves extremely well, rise to the top and perform in an exemplary way as residents and faculty,” Black says.

“In medicine now, patients shop for not only the phenomenal physician, but also someone to connect with and comfort them,” Perry says. “It’s who we are and what we do, and we’re showing you can have it—and do it—all.”

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What’s in Your Office?

From Iron Man to Anchorman

1.

2.

When he isn’t performing pioneering procedures on some of Cedars-Sinai’s tiniest and most vulnerable patients, interventional cardiologist Evan Zahn, MD, might be found on a medical mission in Tanzania, lecturing in China or conducting research in Ireland.

His family helps ground Zahn, director of the Guerin Family Congenital Heart Program at the Smidt Heart Institute. Here, he offers Discoveries a glimpse into his inner sanctum in the Advanced Health Sciences Pavilion, shares treasures from his travels— and explains his admiration for Ron Burgundy.

2. Animation lighting artist Cheryl Davis was the world’s first patient to receive an implantable device to repair congenital heart defects without open surgery, with Zahn as her surgeon. As a thank-you, she had world-renowned Disney animator John Musker draw this caricature of her and Zahn.

3. Today’s 3D printing technology allows Zahn and his team to practice surgeries on exact replicas of patients’ hearts before the actual procedures.

4. Bringing this cowhide shield and spears—made by the Maasai people—home to Los Angeles was “an event,” recalls Zahn, who received the gift following a presentation in South Africa.

4.

3.

5. A photo of the Golden Gate Bridge under construction provides a daily reminder of the importance of building relationships.

6. A former endurance athlete, Zahn no longer participates in Iron Man challenges, but this memory of his 2011 feat spurs him through long days of surgery.

7. Shortly after the fall of the Berlin Wall, Zahn—then a U.S. Air Force major—swapped hats with a major in the Russian military on a mission trip to St. Petersburg.

5.

7.

6.

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Rachael Porter

1. Zahn and several colleagues from around the country share an affinity for Ron Burgundy—Will Ferrell’s iconic character. “We think Anchorman is a monumental movie,” Zahn says. “As a running joke, we give each other little gifts, like this bust.”

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In This Issue 24 Not Lost in Translation

18 The DNA Decoder

28 No Time for MS

22 Frontline Care

Communities most at risk for cancer are among those receiving the least medical attention. Now, Cedars-Sinai investigators are using a culturally tailored approach to reduce disparities in prevention and treatment—from Koreatown to LGBTQ populations.

Scientists don’t know what causes multiple sclerosis or how to stop its attack on the nervous system. But more sensitive diagnostic tools and powerful new medications are helping patients like Amy Fire thrive.

Genetic counselor John Lee of the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute discusses game-changing advances related to genes, the proactive power of DNA testing—and why consumers may be buying bad science.

Cedars-Sinai trauma surgeons share what it’s like to treat gunshot victims, their medical perspectives on the increase in gun-related deaths and how they maintain objectivity as they address this growing public health problem.

34 A Race Against Lightning

The pregnancy disorder preeclampsia can strike in a flash, endangering both mother and child. A dream team at Cedars-Sinai is determined to render this disease—a leading cause of maternal mortality—a relic of the past.

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