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IN THIS ISSUE

Neuroscience + IBD + Cancer + Genomics + Pathology + Immunology + Cardiovascular Disease + Stem Cells + Influenza

FALL 2014

MOUNT SINAI SCIENCE & MEDICINE T H E M AG A Z I N E O F T H E M O U N T S I N A I H E A LT H S Y S T E M

TEAM SCIENCE

Energy • Trust • Challenge • Inspiration


MOUNT SINAI SCIENCE & MEDICINE

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VOLUME V, NUMBER 1

CHIEF EXECUTIVE OFFICER AND PRESIDENT MOUNT SINAI HEALTH SYSTEM

Kenneth L. Davis, MD ANNE AND JOEL EHRENKRANZ DEAN, ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI PRESIDENT FOR ACADEMIC AFFAIRS, MOUNT SINAI HEALTH SYSTEM

Dennis S. Charney, MD CHIEF DEVELOPMENT OFFICER SENIOR VICE PRESIDENT FOR DEVELOPMENT MOUNT SINAI HEALTH SYSTEM

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Mark Kostegan, FAHP EDITOR

Celia M. Regan ASSISTANT EDITORS

Anna Horton Vanesa Sarić CONTRIBUTORS

Travis Adkins Sara Daniels Don Hamerman Andrew Lichtenstein Susan Kreimer

Great minds think...together.

Barbara J. Niss

In this issue, it’s all about teams whose shared goals push

James Nubile

them toward success. And success has many different faces

Sima Rabinowitz

in biomedicine: neurosurgeons launching a moonshot;

Katie Quackenbush Spiegel Neil Webb DESIGN

Taylor Design Mount Sinai Science & Medicine is published twice annually by the Office of Development, Mount Sinai Health System, for an audience of friends and alumni. We welcome your comments; please contact us at a magazine@mountsinai.org or call us at (212) 659-8500. Visit us on the Web at philanthropy.mountsinai.org

two journalists, a group of doctors, a fruit fly, and a brave patient filled with hope; immunologists patrolling the vast nexus of inflammation and disease; pioneers in IBD and their 21st century counterparts; the scientists and mathematicians using massive data sets to pinpoint personalized treatments. Doctors from the spectrum of disciplines bring together their minds and energies to solve the mysteries of cancer, Alzheimer’s, IBD, cardiovascular disease, diabetes— and all the illnesses and conditions that beset humankind. That’s teamwork.

ABOUT THE COVER Leading the Mount Sinai team: Dennis S. Charney, MD and Kenneth L. Davis, MD Photography by Don Hamerman

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CONTENTS

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FEATURES MESSAGE 02 Collaboration is at our core

NEWS 03 A conversation with Dr. Kenneth L. Davis +

08    The Dean on the Team

Record-breaking campaign closes at $1.5 billion

 Why you can’t do it alone.

GIVING

10    Moon Shot

50 Campaign Q & A + By the numbers + Celebrating the Dubin Breast Center, the Council of Advocates, Greening Our Children, the Mirken Family Clinical Neuroscience Institute, the Jaffe Food Allergy Institute, the Children’s Growth Center, and the Crystal Party

ALUMNI 56

Team Science

Profile: Howard Levin + Jacobi Medallion +

Deep brain stimulation may be a game changer for Parkinson’s.

16    Team IBD  Having defined Crohn’s, Mount Sinai leads efforts to tackle it.

22    Triple Negative  The most lethal of breast cancers meets its match.

Reunion 2014 + Society of Alumni Leaders 60 In Memoriam: Six Trustees

26    Next-Generation Sequencing  Pathologists and genomic scientists team to screen for malignancies.

30    On Patrol  Immune cells —and immunologists—keep watch.

36    Going Deep  Stem cells, genetic mutations, and nanoparticles may point the way to preventing heart failure.

40    Cellular Dream Team  Stem cells make up the perfect team.

42    When Pigs Fly  Preventing the next influenza pandemic is the Holy Grail for virologists.

44   Dialogue: Team Stephanie  Fruit flies point the way to personalized cancer therapeutics.

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Mg

MESSAGE

Message from

THE CEO      THE DEAN

&

Anyone familiar with science and innovation knows that discoveries do not happen in isolation. The myth of the lone pioneer in the lab is just that—a myth; the reality is that great scientists and clinicians are part of great teams. The sports metaphor, while perhaps tired, is still apt. As with any athletic team, each member provides an essential component, and together all the players focus their energies on the goals that inspire them and bring out their best. But in science and medicine, even great teams cannot function alone. They need other teams for what they can provide: opposing views, support, insight, perspective. The complex interaction of all these elements is what truly drives brilliance. It can also make for surprises, setbacks, tension, and even disappointment, yet we recognize that crafting new knowledge cannot happen without the delicate balance of challenge and achievement. At Mount Sinai, collaboration is a core value, central to everything we do. As you will read in these pages, we believe deeply in the essential power of team science, and in our own respective roles we facilitate that power every way we can. Each

At Mount Sinai, collaboration is a core value, central to everything we do.

aspect of what Mount Sinai does reflects the importance of collaboration, from the most intricate scientific inquiry, to the strongest network of care for a patient, to the construct of a single leadership board committed to guiding and supporting our work. And, of course, we also respect the model of teamwork beyond science; our recent merger with the former Continuum Health Partners—resulting in the Mount Sinai Health System, an academic medical center comprising seven hospitals and the Icahn School of Medicine at Mount Sinai—has resulted in a new kind of entity that we believe is equipped to handle the challenges and realities of 21st-century American health care.

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

As we celebrate the new Health System and the close of our historically successful

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Campaign for Mount Sinai, we look ahead to the new challenges that await us, confident in the teams—existing, in formation, and not yet dreamed of—that will accomplish our most critical priorities. Kenneth L. Davis, MD CEO and President, Mount Sinai Health System

Dennis S. Charney, MD Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai President for Academic Affairs, Mount Sinai Health System

For individual interviews with Drs. Davis and Charney, please see pp 03 and 08.


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NEWS Merger: The Vision for the Mount Sinai Health System A Conversation with Dr. Kenneth L. Davis

Q

What sparked the merger with Continuum

For example, if you feel responsible for meeting all

Health Partners?

the obstetrical needs, the pediatric needs, and the

dr . davis :

behavioral health needs of your community—which Let me put this in the context of the current

can include not only the major psychiatric disorders,

health care climate. We live in an environment where

but addictions and dementia—you are suddenly

the macroeconomics of health care are forcing

faced with reimbursements for those conditions that

providers to do more with less income: There is simply

simply do not cover costs for patients who come with

not enough money to support the health care demands

Medicaid or Medicare.

of our population—and if we are having trouble with it

So what are the choices? It’s unacceptable to say,

in 2014, we are going to have more trouble as the baby

“We’re not going to do behavioral health or obstetrics.

boomer generation enters its peak use of health care.

We can’t provide all the services that we’d like to

In addition, employers cannot afford benefit

provide.” We have never done that in our health care

packages, and patients increasingly look at their

system, and neither have our new partners. So we

premiums or their copays and say, “This is just too

need to find a business model that will work and not

much.” The burden then falls on the health care

compromise our values.

providers to adjust; it is becoming an environment

Consolidation has, across the country, provided that

where no one can afford services that a lot of patients

model by making corporate services far more efficient,

have demanded in the past, and that physicians

combining some clinical programs in a larger system

thought were necessary.

so that you don’t have to have those same clinical

That problem becomes particularly acute for

programs in every hospital, in every facility, that are

hospitals and hospital systems with a strong social

losing so much money—and still meet the community’s

mission and that are committed to meeting the needs

needs. For instance, Mount Sinai St. Luke’s Hospital

of their community regardless of their ability to pay.

is a mile and a half from The Mount Sinai Hospital;

We are increasingly faced with an equation that doesn’t

ambulances can bring patients from the St. Luke’s

equate. In health care, geography is destiny.

emergency room to the Mount Sinai emergency ➔

“There is simply not enough money to support the health care demands of our population.”

03


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NEWS

room in a matter of minutes: This means we don’t need

Why is teamwork important? Could the health

pediatric ICUs, for example—which are enormously

system have moved forward without it?

expensive—in both places. And not only can we provide more efficient care by putting it all in one place, but we can provide higher quality care. When you deal with rare or complex conditions, outcomes correlate with the quantity of patients you take care of.

dr . davis :

This is not an easy process. Integration of

health care services across multiple hospitals requires teamwork. To begin with, this is a matrix management system—and superimposing that system on a medical school adds even more complexities that require people to work in teams. The faculty and managers who are successful in the Mount Sinai Health System are those

And how will the merger prepare us for the future? dr . davis :

The future of health care is to move away

from fee-for-service medicine, and to move toward population management. What does population

“This is not an easy process. Integration of health care services across multiple hospitals requires teamwork.”

management mean? It means shared risk. It means shared savings. It can mean capitated payments— when we receive a fixed amount of money to take care of a patient, no matter what we do for that patient. Population management changes the focus of care from waiting until a patient is ill (and getting paid to treat every piece of that illness), to getting paid to manage a population and to keep people well. By keeping people well, the money we don’t spend is preserved for other needs.

who understand that autocratic decisions don’t work, that decisions have to be derived by groups, and done so consensually. And processes have to be executed, operationalized, in teams as well. Those teams cut across hospitals and disciplines. Take cancer: Yesterday, we sat down and began to talk about how we can achieve excellence in cancer across all our hospitals, thinking about which programs must be in all the hospitals, and which should only be in a few. We need to engage surgeons, oncologists—the surgeons from different fields, and the oncologists from different areas—and the hospital management teams that will have to facilitate the decisions that are ultimately made. That is an exercise in teamwork.

I s our new health system an appropriate model for others, or is our situation, our profile, more idiosyncratic? dr . davis :

Consolidation and integrated health care

systems are becoming the pattern all over the country. The biggest and most successful integrated health care systems are capable of taking risks, have the best financial performance, and have the best quality. We in New York City have been a little slow to do this. What differentiates us from the others is the significance and excellence of our medical school. If you look at

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

the big models of successful integrated health care

04

What’s Mount Sinai going to look like in five years? In fifty years?

systems, they don’t have at their core a prominent and

dr . davis :

excellent medical school. Because our medical school

nents of the Mount Sinai Health System feel as if they

and our hospital are one, and our culture ensures

are one entity—that they are not separate hospitals

that they work together and our goals are aligned,

or separate clinics, but part of a greater and integrated

we can put an academic medical school—a very,

institution. Our larger identity must trump any

very important medical school for its research and

individual vision. In the longer term, what I see is that,

education missions—at the core of an integrated health

with the continued growth of science, innovation, and

care system. That’s never been achieved. Our hospital

research, and the prominence of our medical school,

is moving towards real integration, and our medical

combined with the robustness of a large, integrated

school essentially reports to the same board as our

health care system, we will be among a handful of

hospital. And that’s unique.

leaders in health care in the world.

Our goal for five years is that all the compo-


Record-breaking Campaign Closes at $1.5 Billion

The Campaign for Mount Sinai: Special Place,

our donors, we are making discoveries that can

Special Time officially closed on December 31, 2013,

revolutionize how we understand and treat the

raising a record-breaking $1.5 billion in philanthropy

major diseases of our time. This is truly a new era

and representing the most successful fundraising

of achievement for Mount Sinai.”

initiative in Mount Sinai’s history.

Launched in 2007, the Campaign has fueled an

“Not only did the Campaign achieve 50 percent

extraordinarily dynamic period in Mount Sinai’s

above our initial goal, but it has been successful

162-year history. It was supported by nearly 40,000

despite the greatest recession of our generation,” said

donors, more than three-quarters of whom were

Mark Kostegan, FAHP, Chief Development Officer

first-time donors to Mount Sinai. The Campaign’s

of the Mount Sinai Health System. “Despite the

historic success reflects a growing philanthropic

economic uncertainty, our Trustee leadership, physi-

community; together Mount Sinai’s supporters have

cians, scientists, and development staff remained

enabled the institution to assemble the infrastructure,

relentlessly devoted to the Campaign’s success. The

technology, and expertise necessary to accelerate

results have been truly remarkable.”

scientific discovery and clinical innovation. Mount

“The Campaign has helped to sustain Mount Sinai’s

Sinai also received unprecedented levels of support

reputation as an outstanding academic medical

from its Boards of Trustees, whose collective gener-

“ All of our donors have given in a way that is important to them and they have propelled Mount Sinai into a position of strength and leadership.”

center,” said Kenneth L. Davis, MD, Chief Executive

osity accounted for nearly half of all giving, as well

– Peter W. May

Officer and President of the Mount Sinai Health

as nearly a third of all gifts over $1 million and more

System. “Because of the remarkable generosity of

than two-thirds of gifts of $10 million or greater. ➔

Pictured above: Dr. Kenneth L. Davis, James and Merryl Tisch, and Peter W. May; Peter W. May, Leni May, and Dr. Dennis S. Charney; James Tisch’s mother, Wilma Stein

05


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NEWS

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Trustee James Tisch, Dr. Dennis S. Charney, and Trustee Richard A. Friedman

06

“All of our donors have given in a way that is

percent. Together, these remarkable accomplishments

important to them and they have propelled Mount

have already begun to produce groundbreaking

Sinai into a position of strength and leadership,” said

achievements in cancer, cognitive, neurodegenerative,

Peter W. May, Chairman of the Boards of Trustees of

and psychiatric diseases, stem cell research, cardiovas-

the Mount Sinai Health System. “In the years to come,

cular disease, genomics, and children’s health, among

the Campaign for Mount

other fields.

Sinai and its supporters

The Campaign also inspired the renaming of the

will be remembered as

medical school as the Icahn School of Medicine at

having played a major role

Mount Sinai, in honor of Trustee Carl C. Icahn, in

in advancing new drugs

recognition of his nearly $200 million in support. In

and therapies for cancer,

addition to vastly expanding its research enterprise,

Alzheimer’s disease, heart

the Icahn School of Medicine continues to attract the

failure, diabetes, and

highest-caliber students and revolutionize medical

countless other diseases,

and graduate education through innovative curricula,

and in helping establish

new admissions standards, and a growing network

a robust platform for

of collaborations with other institutions that provide

addressing continuing

students with one-of-a-kind learning and training

frontiers in medical

opportunities.

research and patient care.”

“The Campaign for Mount Sinai has helped secure

Trustee James S. Tisch, who chaired the Campaign,

our position at the vanguard of medical progress,” said

“The Campaign for Mount Sinai has helped secure our position at the vanguard of medical progress.”

added, “It has been phenomenal to behold Mount

Dennis S. Charney, MD, Anne and Joel Ehrenkranz

Sinai’s metamorphosis and to see up close and

Dean, Icahn School of Medicine at Mount Sinai and

personal the overflowing generosity extended towards

President of Academic Affairs of the Mount Sinai

Mount Sinai during the Campaign, which will enable

Health System. “As a result of the immense generosity

the institution to continue to grow and to excel.”

the Campaign has inspired, we have implemented

Philanthropy powered Mount Sinai’s transfor-

a strategic plan focused on accelerating biomedical

mation over the course of the Campaign, enabling the

research and translating discoveries in the lab to

institution to make crucial investments in intellectual

treatments that change the lives of patients. The

– Dennis S. Charney, MD

capital, state-of-the-art facilities, and technological

urgency of our work and our culture of collaboration

infrastructure. By 2015, more than 275 new recruits

have helped us attract world-renowned scientists and

and 1,000 new postdoctoral fellows in a wide array

physicians who are working together across disci-

of fields will have joined Mount Sinai, energizing the

plines to drive innovation and to make discoveries

institution’s research enterprise and solidifying its

that will advance the way we understand, predict,

reputation as a world leader in academic medicine.

diagnose, and treat human disease. Thanks to our

Mount Sinai has also launched 21 strategic institutes

donors, we have the momentum and the resources

to drive multidisciplinary, translational research

necessary to lead the revolution in biomedicine.”

in key areas, including brain, cancer, and genomics. Mount Sinai’s research budget has grown by more than $82 million, while the Leon and Norma Hess Center for Science and Medicine added nearly 500,000 square feet of new clinical and research space and increased Mount Sinai’s research footprint by 30

To see videos about the Campaign for Mount Sinai and to learn more about its accomplishments, visit philanthropy.mountsinai.org


It takes more than a uniform. Great teams share commitment to a driving vision, a need to bring an idea to fruition, and a powerful recognition: Precious little can happen without the team, fully engaged.

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THE

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

ON THE

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Mount Sinai Science & Medicine recently sat down with Dennis Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine and President for Academic Affairs of the Mount Sinai Health System. The topic is one close to his heart: building outstanding teams to advance innovation. You’re leading Mount Sinai in a direction that relies on putting together special teams, teams that can take us into new areas. Why is this so important for Mount Sinai to do? DR. CHARNEY: Great institutions are essentially made

up of great teams in the areas that are important to that institution. We have a tripartite mission of providing an

outstanding education to the next generation of leaders in science and medicine; discovering breakthroughs that change the way we practice medicine; and providing unprecedented excellence in clinical care. To do that, we need to have great teams—individuals who work together, who synergize, who build on each other’s skills. You can’t do it alone. Science is too complex: The knowledge needed to become a physician and scientist is enormous, and clinical care requires experts from many different disciplines to provide the best care.

As dean, what’s your role in ensuring that the institution keeps and burnishes its great teams? DR. CHARNEY: As dean, I recruit outstanding individuals to

come to Mount Sinai. It’s all about recruitment, and providing the environment for our educators, our scientists, and our clinicians to do the best work they possibly can do. I also have to make sure they fit into our environment, which emphasizes teamwork and collegiality, combined with great ambition.


Cures for complex diseases may require generations of teamwork. How does a team of researchers function at the highest levels of creativity, energy, and optimism, knowing that they are part of a much longer process? DR. CHARNEY: Science does require patience. Sometimes

great findings come from unexpected directions. To create the environment in which breakthroughs occur, we have to emphasize several things. First, innovation must be the norm—and that means that we have to accept failure. In fact, my view is that if people don’t fail, they’re not pushing the envelope enough to see what’s possible. So we strive to create an environment in which failure is part of the learning process. And we want to be entrepreneurial. One of the reasons that companies such as Google and Apple and Facebook have changed our world is that they value energy, creativity, disruptive thinking. At Mount Sinai, at every level, from students to junior faculty to senior faculty and institutional leadership, we have to be open to new ideas that shake the foundations of what we have been used to.

Can a leader lose his or her ability to lead over time? DR. CHARNEY: Leaders must continue to reinvent themselves and

reinvigorate their vision or they will lose the ability to inspire. Understandably, people cannot stay in leadership positions forever. A good leader knows when it’s time to step down and to bring in a new leader with a new vision and a different way of doing things.

Is there a down side to having a strong leader? DR. CHARNEY: Sometimes an institution can take on the persona

of the leader. Is there a danger in that happening? Yes. Institutions defined by a single leader tend to fall back when that leader steps down. Here, the senior leadership is committed to Mount Sinai as an institution, not defining the institution based on who the current leader is. That’s very important.

You have a critical responsibility in empowering leaders to build teams of their own. What do you look for in a leader? DR. CHARNEY: I look for a number of different characteristics:

Why is it sometimes challenging for institutions to move away from the rigidity of the accepted norm? DR. CHARNEY: You are most comfortable when your

environment is predictable. Some people have difficulty when their accepted truths are confronted. It’s an attitude that stunts growth, which we cannot accept. But conflict, in the right environment, can breed forward motion and new discoveries. If people are not open to having their ideas confronted in a helpful and healthy spirit—if there’s not intense discussion and searching for answers—then creativity is stifled and discoveries don’t happen.

Is conflict itself a challenge for a dean? DR. CHARNEY: Yes, the dean has to be comfortable with

conflict and provide an open, transparent, and positive environment. Strong interpersonal relationships built on trust allow one to have the kinds of intense interactions that in some magical way can lead to great new ideas.

to be able to count on your team members to look out for you and for the success of the team. The leader must make sure that every member of the team buys into the team concept, and not tolerate members who are not out for the good of the team—that can bring down the performance of the entire team.

come to Mount Sinai. It’s all about recruitment, and providing the environment for our educators, our scientists, and our clinicians to do the best work they possibly can do.”

What do you see as the future for Mount Sinai over the next three to five years? DR. CHARNEY: Mount Sinai is perhaps at the most transformative

time in its history. The School of Medicine is on the threshold of world leadership in education and scientific breakthroughs in areas such as heart disease, cancer, brain diseases, and others. It is my intention to keep the momentum going to achieve that aspiration. Our environment, our resources for scientists and clinicians, our structure—everything must allow them to function at the optimal level. ❉

SCIENCE

DR. CHARNEY: Trust has to occur at every level. You have

As dean, I recruit outstanding individuals to

TEAM

How do you facilitate trust within teams?

a compelling vision, a roadmap to achieve that vision, and the ability to pick and maintain a team that’s going to be successful. It’s helpful if they have a strong dose of humility and a sense of altruism. The leaders who generate the most loyalty are those who know that it’s not all about their own accomplishments, but about the accomplishments of others around them.

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A team of surgeons, neurologists, psychiatrists, and neuroscientists make deep brain stimulation possible.

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

MOON SH T

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BY TRAVIS ADKINS PHOTOGRAPHY BY ANDREW LICHTENSTEIN ILLUSTRATION BY NEIL WEBB


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he first time it happened, Michael Toscano thought it was the adrenaline. He was a rookie cop with the NYPD, working the midnight shift in Brooklyn and responding to a radio call, when his leg began shaking uncontrollably. The shaking passed, and he chalked it up to a rookie’s nerves and thought no more of it. Then it happened again, and again. Finally, one evening while taking a test at the night school where he was studying mortuary sciences—Mr. Toscano moonlighted as a funeral director for many years—all of a sudden he couldn’t write. “It was just like someone turned a light switch off,” he recalls. “My brain was telling me what to write, but my hand

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

wasn’t working. I knew something was wrong.”

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MR. TOSCANO’S PERCEPTION OF A LIGHT SWITCH being turned off was not far from the truth: He had Parkinson’s disease. In the substantia nigra region at the base of his brain, which plays a central role in motor control, the nerve cells that produce dopamine—the neural chemical that transmits the electrical signals which tell the body to move—were slowly dying. Over the next few years, the disease steadily worsened. A daily regimen of drugs such as L-Dopa controlled the worst of the tics and tremors. Mr. Toscano persevered with the help of his wife and three daughters, who immersed themselves in learning everything they could about Parkinson’s disease, and with friends like his lieutenant at the NYPD, who quietly allowed him to use his left hand to fulfill the requirement of being able to draw and present his gun on command. Most of all, though, what kept him going

was a tenacious spirit and a deep reserve of courage. At last, however, he reached a crossroads. The drugs were no longer effective. “The dyskinesia and dystonia were so bad that just moving every day was impossible,” says Mr. Toscano. “My neurologist told me he couldn’t do anything else.” His last, best hope lay in a revolutionary procedure that is not only changing the way we treat Parkinson’s disease and other movement disorders, but is offering promising new directions in major depression, drug addiction, and many other neuropsychiatric disorders. It’s called deep brain stimulation (DBS), and the team of neurosurgeons, neurologists, psychiatrists, and neuroscientists from Mount Sinai’s Center for Neuromodulation are using it to turn the lights back on for Mr. Toscano and hundreds of other patients like him.


Because of the talented team at Mount Sinai, I can function again.” – Michael Toscano

GETTING INTO A RHYTHM

TEAM

Left: The stereotactic headframe and intraoperative CT scan Right: An example of the brain activity recorded during a DBS procedure

SCIENCE

In essence, DBS works by jolting the brain’s malfunctioning electrical currents back into their natural rhythm through a wristwatch-sized device called a neurostimulator. A neurosurgeon threads a small wire with an electrode at the end through an opening in the patient’s skull until the electrode reaches the target spot. That wire and electrode are then connected, via another small extension wire, to the neurostimulator, which is implanted just under the patient’s skin near his collarbone. In the weeks and months after the surgery, a programming expert finely calibrates the neurostimulator’s settings, such as amplitude and frequency, to deliver just the right “dose” of electrical impulse. The expertise necessary to perform such a technically demanding operation spans multiple disciplines, from the neurologist who makes the initial recommendation for the surgery and manages

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Above and right: Michael Toscano meets Dr. Kopell

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Below right: Dr. Kopell and his assistant, Brendan Sullivan, PA, implanting the DBS electrode

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the patient’s care afterwards, to the imaging experts who ensure that the neurosurgeon has a precise target, to the programmer who adjusts the neurostimulator’s settings to optimize the effect, and many more. “I liken it to launching a moonshot,” says Brian Kopell, MD, the Director of the Center for Neuromodulation, Professor of Neurosurgery, Neurology, Psychiatry and Neuroscience, and a leading neurosurgeon who has performed the procedure more than 800 times. “It takes many different experts to launch a spacecraft. In deep brain stimulation surgery, there’s a lot of work that has to be done from many different disciplines. And it’s often in areas that are not used to working with one another. The Center for Neuromodulation breaks down traditional silos in favor of a therapy-based approach.” In Mr. Toscano’s case, that “moonshot” was not just one giant leap, but two. He first underwent the procedure at Mount Sinai in 2009; although it was a success, two years later he developed a serious infection around one of the electrodes, requiring its removal and re-implantation.

But the setback turned out to be to his advantage. In the interim since his first operation, Dr. Kopell introduced a new intraoperative imaging technology that allowed him to place the electrodes with even greater precision, which in turn meant that the neurostimulator’s settings could be adjusted more effectively. “I thought that was amazing,” Mr. Toscano says.


UNLOCKING THE SECRETS OF THE “BLACK BOX” Dr. Kopell’s pioneering use of the intraoperative imaging technology is just one of the ways that Mount Sinai is advancing the field. Under the leadership of Dr. Kopell and Wayne Goodman, MD, Chair of the Department of Psychiatry, Professor of Neuroscience, and Acting Site Chair of Psychiatry and Behavioral Health at Mount Sinai Roosevelt and Mount Sinai St. Luke’s, the Center for Neuromodulation has won approval from the Food and Drug Administration to use deep brain stimulation to treat patients with severe, refractory forms of Tourette’s syndrome, obsessive-compulsive disorder, and depression, and the group is seeking approval to test the treatment in severe cases of cocaine addiction and anorexia nervosa. A relatively small number of all patients are considered to have a condition dire enough to warrant the treatment, but for those who qualify, the results are transformational. Patients are able to gain control over their lives for the first time in years, and while their outcomes are still being tracked to determine long-term efficacy, the early results indicate that DBS offers a lasting benefit. Furthermore, because DBS enables researchers to test directly which circuits and regions in the brain are involved in certain disorders—a rare opportunity in brain – Dr. Brian Kopell research, which usually must rely on indirect

The Friedman Brain Institute (FBI), the hub for translational neuroscience at the Icahn School of Medicine, and at The Mirken Family Clinical Neuroscience Institute, which coordinates and unites clinical neuroscience activities across the entire Health System. Their work may lead to new therapeutic applications for deep brain stimulation. FBI members Scott Russo, PhD, Associate Professor of Neuroscience, and Ming-Hu Han, PhD, Assistant Professor of Pharmacology and Systems Therapeutics, are each using optogenetics—an emerging research tool that enables neuroscientists to activate the neurons they want to study by genetically modifying them to be susceptible to light—to identify areas of the brain that are involved in depression, which could yield additional targets for deep brain stimulation treatment. Mark Baxter, PhD, Professor of Neuroscience, Anesthesiology, and Geriatric and Palliative Medicine, is studying how DBS may be effective for Alzheimer’s disease and other memory and cognition disorders, as is Matthew Shapiro, PhD, Professor of Neuroscience and Geriatrics and Palliative Medicine, whose laboratory was the first to use DBS to induce specific, coordinated rhythms—theta and gamma rhythms—and improve memory storage and retrieval in an animal model.

I liken it to launching a moonshot. It takes many different experts to launch a spacecraft. In deep brain stimulation surgery, there’s a lot of work that has to be done from many different disciplines.”

SCIENCE

The experts who comprise the Center for Neuromodulation are an impressive collection of talent—and, as with any other team, their success is more than the sum of their individual strengths. It is their shared vision and mutual commitment to improving patient’s lives that drive the Center’s work. “The patients we refer for deep brain stimulation are generally patients we have known for years; we know their families and their social situations and their response to medications and treatments in the past,” says Susan Bressman, MD, Chair of the Mirken Department of Neurology at Mount Sinai Beth Israel, Chair of Neurology at Mount Sinai Roosevelt and Mount Sinai St. Luke’s, and Professor of Neurology, noting that more DBS procedures are performed at Mount Sinai than any other New York City-area hospital. “We have a real understanding of where our patients are coming from.” Michael Toscano couldn’t agree more. Today, thanks to his successful operation, he can enjoy many of the activities that were previously impossible for him, such as riding a bike and driving a car. “Because of the talented team at Mount Sinai, I can function again,” says Mr. Toscano. “I thank them for that.” ❉

TEAM

methods to prove a hypothesis—it can shed light on the structure and mechanics of the brain and provide valuable insight for drug discovery and other non-surgical therapies. “It’s a unique opportunity to learn about these disorders, and to develop less invasive treatments,” says Dr. Goodman. Eric Nestler, MD, PhD, Director of The Friedman Brain Institute, Nash Family Professor of Neuroscience, and Chair of the Department of Neurosciences, echoes Dr. Goodman’s point and explains that while clinicians and researchers know that DBS works, they don’t yet know how or why, and answering those questions could vastly expand its potential. “Right now, deep brain stimulation is like a black box,” says Dr. Nestler. “It might work by activating nerve cell bodies, or by shutting them down. Or maybe it’s not the cells, but the nerve terminals adjacent to those cells; or maybe it’s none of the above and instead it works by stimulating nerve fibers that are passing through a particular region of the brain. Those are big questions.” The Center for Neuromodulation is working to answer those questions through close collaboration with research colleagues at

MORE THAN THE SUM

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BY SIMA RABINOWITZ

Dr. Sands, Dr. Ashish Atreja, Director of I-ROQ (Informatics for Research Outcomes and Quality), and Dr. Carmen Argmann, who is part of the Biological Datamining Group at the Icahn Institute for Genomics and Multiscale Biology, have come together with colleagues across the institution to advance what is perhaps the single largest collaboration ever undertaken at Mount Sinai: a research alliance with Janssen Research and Development and Johnson & Johnson to investigate disease triggers that contribute to IBD and develop, patent, and license new therapies for clinical application.

PHOTOGRAPHY BY ANDREW LICHTENSTEIN

Dr. Bruce Sands, Chief of the Henry D. Janowitz Division of Gastroenterology, and Dr. Jean-Frédéric Colombel, The Leona M. and Harry B. Helmsley Director of The Leona M. and Harry B. Helmsley Charitable Trust Inflammatory Bowel Disease Center, have, with others, described the efficacy of the novel therapy vedolizumab to treat Crohn’s disease and ulcerative colitis.

Dr. Joel Dudley’s partnership with his colleagues is unique— he has Crohn’s disease; Dr. Sands is his doctor.

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Dr. Bruce Sands

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Dr. Ashish Atreja

Dr. Joel Dudley

Dr. Carmen Argmann

Dr. Brian Kidd


“In IBD, everybody is collaborating with everybody,” says Dr. Bruce Sands, who would know: He is leading a big, multidisciplinary investigation into IBD (the standard abbreviation for inflammatory bowel disease), which includes Crohn’s disease and ulcerative colitis. It would take computational technologies nearly as powerful as the ones “Team IBD” at the Icahn School of Medicine at Mount Sinai uses for analyzing their research data to map the team’s extensive network of collaborations and partnerships.

Dr. Colombel and Dr. Jeremiah Faith, Assistant Professor of Genetics and Genomic Sciences, are collaborating on innovative research exploring the relationship of diet to IBD.

Dr. Jean-Frédéric Colombel

Dr. Judy Cho

Dr. Jeremiah Faith

Dr. Inga Peter is collaborating with her colleague, Dr. Judy Cho, Ward-Coleman Chair in Translational Genetics, Dr. Brian Kidd, a biomedical informatics scientist, and Dr. Dudley, Director of Biomedical Informatics, to find potential targets, based on their identification of genes implicated in IBD, for drug discovery and repurposing.

Dr. Noam Harpaz

Dr. Sergio Lira, Director of the Immunology Institute and The Leona M. and Harry B. Helmsley Charitable Trust Professor of Immunology, develops animal models to test genetic findings provided by Dr. Inga Peter and Dr. Judy Cho in the Department of Genetics and Genomic Sciences and collaborates with Dr. Faith to test if these genetic changes can induce disease by interacting with the microbiome (the bacteria, “good” and “bad,” in our bodies).

They consult with Dr. Noam Harpaz, Professor of Pathology, who identifies disease states in humans and in their models’ tissues and organs.

TEAM

Dr. Sergio Lira

SCIENCE

Dr. Inga Peter

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In addition to all of these, there is a project that plugs the expertise of Team IBD into a national network of IBD research and discovery. Envisioned and directed by the late Dr. Lloyd Mayer [see sidebar, page 35] and supported by The Helmsley Charitable Trust, the aptly named SHARE (Sinai-Helmsley Alliance for Research Excellence) project involves seven premier academic research medical centers across the country dedicated to the study and treatment of IBD. Of specific interest is whether genetic changes in Crohn’s patients promote altered expression of inflammatory molecules. Mount Sinai manages the network, which includes Cedars-Sinai Medical Center, Massachusetts General Hospital, Mayo Clinic, the University of Chicago Pritzker School of Medicine, the University of North Carolina at Chapel Hill, and Washington University School of Medicine. At Mount Sinai, members of the Immunology Institute, including Drs. Colombel and Lira, collaborate with colleagues in the Henry D. Janowitz Division of Gastroenterology and the Department of Genetics and Genomic Sciences, including Drs. Sands, Peter, and Atreja, and Steven Itzkowitz, MD, Professor of Medicine, Gastroenterology, and Director of the Gastroenterology Fellowship Program, to study the inflammatory components of the disease.

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

“Cracking” Complex Human Disease

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The US spends $1.7 billion annually on IBD-related diagnosis and treatment.

Mount Sinai’s commitment to team science, a culture of collaboration, and translational focus can affect an enormous number of patients and their families. More than a million Americans live with IBD: Crohn’s disease, ulcerative colitis, and microscopic colitis—painful, often debilitating conditions. In patients who suffer from IBD, the immune system, triggered by the body’s normal gut bacteria, attacks the digestive system and causes symptoms from mild to extreme abdominal discomfort and distress, as well as diarrhea and many other symptoms. The disease is complex, poorly understood, and costly. The best available therapies achieve remission for only 35 percent of patients and there is currently no way

to predict how an individual patient may respond to a given treatment. The Centers for Disease Control and Prevention estimate that the US spends $1.7 billion annually on IBD-related diagnosis and treatment, including more than 700,000 patient visits, 100,000 hospitalizations— surgery is often required for Crohn’s disease—and disability in 119,000 patients. “To crack complex human disease, team science is essential,” says Dr. Cho, a distinguished classical geneticist (“we collaborate for a living”) and steering committee chair of the National Institute of Diabetes and Digestive and Kidney Diseases’ IBD Genetics Consortium for the last twelve years. “IBD is tough, but at Mount Sinai we have an unprecedented opportunity and we’re making substantial progress through our collaborative efforts.”


“IBD is tough, but at Mount Sinai we have an unprecedented opportunity and we’re making substantial progress through our collaborative efforts.” DR. JUDY CHO

The 10,000-Foot View Team IBD’s effectiveness is due, in great measure, to participants’ willingness to learn from and teach each other, find a common vocabulary, and transparency— free and open sharing of data, results, insights, and plans. To support Project SUCCESS (Sinai Ulcerative Colitis Clinical Experimental and System Studies), for example, Dr. Lira explains that it has been important to use plain language both in meetings and consultations and in written documents, rather than specialized jargon associated with specific disciplines (immunology, microbiology, gastroenterology, genetics, computational biology), and to establish a fundamental ground rule: “There are no stupid questions.” Dr. Lira is enthusiastic about his “dream team” and attributes the ability to move forward with momentum and optimism not only to the willingness to learn from each other,

but to reframe research questions and points of reference to create a different and new understanding of the biological mechanisms underlying disease. His perspective is echoed by every member of Team IBD. “I like to say that we provide the ten-thousand-foot view,” explains Dr. Dudley. Where a geneticist might, for example, request analysis of a single gene, computational biologists, once they possess the genetic data, may suggest analysis of every gene in the genome related to the question at hand, so that the results may have much larger implications, identify more targets, and, consequently, point with great precision to potential and personalized new therapies for multiple diseases. At the same time, “our naïve questions,” says Dr. Sands, may not occur to the experts in a given field, which can also produce new insights and prompt novel approaches to prevention, diagnosis, and treatment.

Startling Images

TEAM SCIENCE

“Here’s what we’re trying to solve!” says Dr. Argmann. At a meeting of the Mount Sinai Janssen Project team, Dr. Colombel eagerly showed graphic images of Crohn’s disease and ulcerative colitis. The computational biologists had not before been so intimately connected to the realities of the disease; and for most it was the first time they had seen the manifestations of these diseases in real-life images, explained by real-life clinicians. “These awful slides were the very image of what we were trying to model through our networks,” says Dr. Argmann. “The disease was no longer an abstraction or an algorithm,” she says. “I came to Mount Sinai because of this opportunity to collaborate and work with all scales of biology, from the clinic to the lab to the computer. Here, we’re able to get a true understanding of what IBD really looks like by developing relationships with clinicians, and having access to diverse patient populations and then capturing vast amounts of data and employing the computational capacities of Minerva [Mount Sinai’s supercomputer and one of the fastest data sequencers in the world], to generate the computational solutions of the networks, with the end goal of getting to the best therapies possible for IBD.”

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MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Physicians and Patients are Partners

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Small is Big

A great team needs to play in a worthy venue, and Team IBD is about to get one. Projected to open at Mount Sinai in the fall of 2014, the eagerly anticipated Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center will bring together the highest quality patient care and innovative research in a unified space. The Center will support clinicians in internal/adult and pediatric medicine, surgeons, nurse practitioners, and research scientists. “To make progress in our work, we need access to a large, wellcharacterized population. We have amassed more than twenty thousand samples related to IBD,” says Dr. Harpaz. “Our hospital has one of the most diverse patient populations in the world.” The Center furthers the connection between patient care and scientific research, facilitating relationships among scientists and clinicians. “Our vision is to have seamless integration of the superb research capabilities at Mount Sinai—supported by The Helmsley Charitable Trust—and our new clinical center, funded by Mr. and Mrs. Feinstein,” says Dr. Colombel. “We have world leaders in IBD research and gifted young investigators dedicated to creating new knowledge to inform clinical care and advance our efforts toward better diagnosis, better quality of life, and eventually cures for IBD.” Dr. Brian Kidd notes that the opportunities for mutual understanding between scientists and physicians are promising, “We can throw on a white coat and shadow a physician in the hospital. We gain understanding of the disease from the doctors’ and patients’ perspectives.” To advance this work, Dr. Atreja is collaborating with Dr. Colombel and faculty partners to develop an Integrated Patient Solution platform (app) to capture patient reported outcomes from patients’ smartphones to be integrated with Electronic Health Record and “-omics” data (characterization and quantification of pools of biological molecules) with the goal of linking patients, physicians, and researchers in a unified effort to improve patient experience and outcomes. The plan is to disseminate the app nationally to contribute to improvement in patient care and outcomes for IBD on a large scale and serve as a model for disease management in a broader way.

“We place a premium on recruiting research leaders and promising young investigators from around the world committed to a team approach who can get along well and seek opportunities to collaborate,” says Dr. Sands. “They come together on one square city block.” Mount Sinai’s institutional resources for collaboration in IBD are vast. Dr. Dudley says Mount Sinai has recruited more than 100 of the nation’s most gifted computational biologists, probably more than any other medical school in the country; most other schools have fewer than a half dozen, he says. Nevertheless, promoting and facilitating team science and advances in IBD are not limited to just the campus: Dr. Colombel has contributed to the launch of the first New York network of IBD researchers and clinicians with

participation from colleagues at Mount Sinai, Columbia Presbyterian, Weil Cornell, and hospitals across the Mount Sinai Health System. Training the next generation of team scientists is important, as well, explains Dr. Peter. “Most of us trained in narrow niches. We’ve created new programs to ensure that the next generation of scientists will be inspired to engage in team science across disciplines early in their careers.” National and international teams are essential, too: Drs. Colombel, Harpaz, Cho, and Peter have undertaken a groundbreaking effort with the participation of several groups from the US and Europe to study the genetics of microscopic colitis; and Drs. Colombel, Faith, and Peter are collaborating with French teams on a study of communities in New York and northern France with an unusually common genetic predisposition to IBD in large families.

THE TEAM Carmen Argmann, PhD, Assistant Professor of Genetics and Genomic Sciences

Ashish Atreja, MD, MPH, FACP, Assistant Professor of Medicine, Gastroenterology; Director, I-ROQ (Informatics for Research, Outcomes and Quality)

Judy Cho, MD, Ward-Coleman Chair in Translational Genetics; Professor, Genetics and Genomic Sciences; Associate Chief of Research; Vice-Chair for Translational Genetics

Jean-Frédéric Colombel, MD, PhD, Director, The Leona M. and Harry B. Helmsley Charitable Trust IBD Center; Professor of Medicine, Gastroenterology

Joel Dudley, PhD, Director of Biomedical Informatics, Icahn Institute for Genomics and Multiscale Biology; Assistant Professor of Genetics and Genomic Sciences and Health Evidence and Policy

Brian Kidd, PhD, Biomedical Software Developer, Genetics and Genomic Sciences


Big is Big If the science of IBD is complex, the logistical and operational aspects of supporting successful cross-disciplinary teams are nearly as challenging. “We’re engaging colleagues from multiple departments, including clinicians who meet with patients every day. The sheer management of schedules is overwhelming,” says Jennifer Walker, Program Manager for the Icahn Institute for Genomics and Multiscale Biology. “Successful team science requires a commitment to adequate administrative support, assistance to manage regulatory requirements, and budgetary considerations.” She is quick to note that team science involves many “invisible” yet indispensable players, as well: lab technicians, graduate students and postdoctoral fellows, and administrative support personnel.

“We’ve created new programs to ensure that the next generation of scientists will be inspired to engage in team science across disciplines early in their careers.” DR. INGA PETER

The IBD Family

Noam Harpaz, MD, PhD, Professor of Pathology and Medicine, Gastroenterology

Sergio Lira, MD, PhD, Director, Immunology Institute; The Leona M. and Harry B. Helmsley Charitable Trust Professor of Immunology; Professor of Medicine, Clinical Immunology

Inga Peter, PhD, Associate Professor of Genetics and Genomic Sciences

A MOUNT SINAI DOCTOR AND RESEARCHER

for more than 60 years, Burrill B. Crohn, MD (center) played a central role in identifying Crohn’s disease—but the name doesn’t reflect that the discovery was very much a group effort. At the direction of the eminent surgeon A.A. Berg, MD, Mount Sinai’s Leon Ginzburg, MD (right), a surgeon, and Gordon D. Oppenheimer, MD (left), a pathologist, began examining bowel disorders and tumors during the late 1920s, while Dr. Crohn pursued his own research and published a text in 1927. Dr. Berg insisted that Drs. Ginzburg and Oppenheimer share their research and a draft paper with Dr. Crohn. When they came together to publish, jointly, their seminal paper, “Regional Ileitis: A Pathologic and Chronic Entity,” in the Journal of the American Medical Association (JAMA) in 1932, Dr. Berg did not want his own name to be included; the other three agreed to an alphabetical listing of authorship. Drs. Ginzburg and Oppenheimer published their own findings in the 1932 AGA Transactions and, expanded, in Annals of Surgery (December 1933). Dr. Crohn’s activities in presenting the diagnosis to a wide audience of physicians, coupled with the fact that his name was first on the JAMA paper, helped make “Crohn’s disease” the name by which regional ileitis was commonly known. But Dr. Crohn and his two co-authors—particularly Dr. Ginzburg—did not get along. “Their towering egos kept them in a state of smoldering animosity for the next fifty years,” write Arthur H. Aufses, Jr., MD and Barbara J. Niss in This House of Noble Deeds. “Nonetheless, as with so many other interdisciplinary efforts at Mount Sinai, Crohn and Ginzburg’s collaboration was incredibly productive and stimulated an unparalleled flow of clinical and laboratory research.”

Bruce E. Sands, MD, Chief of the Henry D. Janowitz Division of Gastroenterology, Dr. Burrill B. Crohn Professor of Medicine, Gastroenterology

Jennifer Walker, Program Manager, Icahn Institute for Genomics and Multiscale Biology

SCIENCE

Jeremiah Faith, PhD, Assistant Professor of Genetics and Genomic Sciences and Medicine, Clinical Immunology

“Sometimes I could wish to have chosen ear, nose, and throat as a specialty rather than the tail end of the human anatomy...” – Dr. Burrill B. Crohn

TEAM

The IBD team thrives on connection. “You need a few key people to propel the work forward,” notes Dr. Faith. “We have weekly, bi-weekly, quarterly, and annual meetings. Some are narrowly focused and others are more broadly focused, with different people at each meeting who have overlapping interests and objectives.” And the team feeling goes beyond essential structures. After he first arrived at Mount Sinai in May 2013, Dr. Colombel invited every colleague across the institution involved in IBD for a Sunday brunch where they explored potential collaborations and tasted some French pastries. One year later, the

group met again to share their progress. “I will always associate our IBD team with delicious French food,” says Dr. Faith. “I met many of the IBD clinicians that Sunday, and I’ve been interacting with them ever since.” “We’re the IBD family now,” says Dr. Colombel with clear pride and warmth. He says he is amazed by the friendships that have developed among the members of Mount Sinai’s vast network of IBD scientists and clinicians, and he is optimistic about the potential to radically improve predictive strategies for IBD and approaches to earlier, more effective treatments. “Our goal is to cure patients, not disease,” concludes Dr. Peter. “This is the greatest benefit of a team approach.” ❉

NAMESAKE

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TRIPLE NEGATIVE BY SUSAN KREIMER

PHOTOGRAPHY BY ANDREW LICHTENSTEIN


On a spring afternoon, a new patient consulted with Amy Tiersten, MD, Associate Professor of Hematology and Medical Oncology and a member of The Tisch Cancer Institute, about the best plan of attack for a devastating diagnosis: metastatic triple-negative breast cancer. Right now, there’s not much hope she can offer, because this is an aggressive malignancy with a limited response to traditional chemotherapy once the disease has advanced to a late stage. “The tumor shrinkage lasts only a short period of time,” Dr. Tiersten explains. DR. TIERSTEN IS PART OF A MOUNT SINAI TEAM of physicians and scientists striving to improve outcomes for patients who must battle a disease that is notoriously resistant to conventional chemotherapy agents. Triple-negative is perhaps the most virulent of breast cancers, multiplying and metastasizing more rapidly, with higher recurrence rates. A triple-negative tumor lacks three common types of receptors that stimulate most breast cancer growth: estrogen, progesterone, and the HER-2/neu gene. As a result, it won’t react to drugs that target these receptors. But soon Dr. Tiersten hopes to present another option to this patient and others in her predicament. As principal investigator, she plans to embark on a clinical trial testing a novel regimen, combining a specific type of chemotherapy with a particular biologic agent that shows promise for prolonging progressionfree survival in patients with triple-negative breast cancer. The multi-center randomized trial is expected

to enroll a total of 144 patients at Mount Sinai and a few other academic medical centers in New York City. It will evaluate whether the oral biologic agent Afinitor (everolimus) would extend progression-free survival when used in combination with Carboplatin, a chemotherapy drug that is particularly active in triple-negative breast cancer. While reluctant to hypothesize, Dr. Tiersten estimates a four-month improvement in survival for patients on the combined regimen. Median survival for patients with triple-negative breast cancer is less than two years. A few additional months may not sound significant, but it’s “our initial signal that there may be some activity and that treatments look promising in the metastatic setting,” Dr. Tiersten says. Such an outcome would encourage researchers to design trials into earlierstage disease with the goal of potentially curing more patients.

CANCER CELL

TRIPLE-NEGATIVE CANCER CELL

PROGESTERONE PROGESTERONE

P

P

Receptors Receptors

P

P

H

H

ESTROGEN PROGESTERONE HER-2/NEU GENE ESTROGEN PROGESTERONE HER-2/NEU GENE

E

E

ESTROGEN ESTROGEN

A triple-negative tumor lacks three common types of receptors that stimulate most breast cancer growth: estrogen, progesterone, and the HER-2/neu gene. As a result, it won’t react to drugs that target these receptors.

E

E

ESTROGEN ESTROGEN

National Breast Cancer Foundation, Inc.

SCIENCE

PICTURED The Triple-Negative team, clockwise from upper left: Hana Yoko Irie, Amy Tiersten, Elisa Port, Ramon Parsons, and Hank Schmidt

E

TEAM

E

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Triple-negative breast cancer constitutes about 15-20 percent of breast malignancies

CRITICAL COLLABORATION

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Dr. Schmidt with Dr. Irie (top and center) and Dr. Port

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But triple-negative is a formidable foe, requiring collaboration among different disciplines: Newly diagnosed patients typically require the expertise of radiologists and surgical oncologists, and in many cases, medical and radiation oncologists as well as plastic surgeons and genetic counselors. Although the breast surgeon “mixes and matches” these disciplines for each patient’s needs, other medical team members play a pivotal role in delivering comprehensive care, says Elisa Port, MD, Chief of Breast Surgery, Director of the Dubin Breast Center of The Tisch Cancer Institute, and Associate Professor of Surgery. “When you sit in a room and discuss cases in a multidisciplinary fashion, you can always be surprised by new ideas,” Dr. Port says. “We bounce off of each other different aspects of treatment, so it’s all for a patient’s benefit to have many different aspects of their care really thought out ahead of time.” An open dialogue and offices within close proximity facilitate teamwork at the Dubin Breast Center. Intent on presenting patients with the best possible options, Dr. Port can approach her colleagues informally and say, “She’s thinking of doing XYZ; how would this affect the treatment you would give?” One of the new paradigms for breast cancer is administering chemotherapy before surgery. Because some tumors may shrink in response to treatment, patients could benefit from consulting with a medical oncologist sooner rather than later. But triple-negative breast cancer plays by its own rules. “We don’t have a targeted therapy for it as of yet,” says Ramon Parsons, MD, PhD, Professor and Chair of the Department of Oncological Sciences and the Ward-Coleman Professor in Cancer Research. Patients “often relapse after surgery, radiation, and chemotherapy. That’s why we need to try to understand the disease better, to identify new ways of attacking it.”

DISPROPORTIONATE IMPACT Triple-negative breast cancer constitutes about 15-20 percent of breast malignancies, occurring more commonly in young women and those with BRCA-1 genetic mutations, thus disproportionately affecting African-Americans and women of Ashkenazi Jewish descent—two groups residing in large concentrations within nearby communities that Mount Sinai serves, including East Harlem. Mount Sinai’s top-notch facilities—from imaging to medical and surgical areas—offer complete care, augmented by strong research. And that research has shown that triple-negative breast cancer acts differently from other breast cancers. A response to the chemotherapy agent Cisplatin indicates that it may have more in common with ovarian cancer, and studies suggest that clinicians should consider using Cisplatin more frequently in triple-negative breast cancer.

TUMOR BANK Enter Mount Sinai’s Bio Bank, a repository of tissue collected from consenting patients. By preserving specimens from every breast surgery—including many triple-negative tumors—the team has created a great research asset. “This resource didn’t exist until about two years ago, when we embarked on this effort,” says Hanna Yoko Irie, MD, PhD, Assistant Professor of Medicine, Hematology and Medical Oncology, and Oncological Sciences. “All of the breast surgeons, medical oncologists, and radiologists at Dubin contribute to this banking effort, so it represents the best of teamwork.” Dr. Irie has written a protocol for collecting and storing tumor specimens in conjunction with two other Mount Sinai team scientists—Hank Schmidt, MD, Assistant Professor of Surgery, who focuses on breast cancer, and Michael Donovan, MD, Professor of Pathology, and Director of Experimental Pathology, Biorepository and Pathology Core. As a physician-scientist, Dr. Irie splits her time between caring for patients at the Dubin Breast Center and supervising a research laboratory that aims to identify novel therapeutic targets for triple-negative breast cancers. “I study how specific ‘driver’ genes propel triple-negative breast cancer cells to grow, divide, and metastasize,” she says, while noting that triple-negative “is a very biologically aggressive subtype of breast cancer that is genomically heterogeneous.”


Dr. Ramon Parsons and a member of his lab team

PIONEER IN A CAREER THAT SPANS MORE THAN six decades, James F. Holland, MD has pioneered

NOVEL STUDY

nary, life-saving discoveries in cancer treatment. Distinguished Professor of Neoplastic Diseases, Professor of Medicine, Hematology and Medical Oncology, and Professor of Oncological Sciences, Dr. Holland is also a master team player. Beginning in 1963, he chaired one of the country’s first collaborative group trials (Acute Leukemia Group B) which included investigators from the US, Canada, and Europe and resulted in some of the first cures of acute lymphoblastic leukemia in children using high-dose methotrexate. Because of his innovative work in combination therapy, the disease went from being previously incurable to having more than an 80 percent survival rate. And today, the survival rate is more than 90 percent. With this same pioneering team of researchers, Dr. Holland established the “7 and 3” treatment regimen for myelogenous leukemia—a treatment that yields significant outcomes for patients and remains the standard induction therapy regimen today; its success has supported the use of intensive chemotherapy in other cancers. He also first identified Cisplatin to treat testicular cancer, improving survival rates from about 10 percent to 80 percent. Dr. Holland’s recent research is centered on determining the cause of certain types of breast cancer. “Jim is a phenomenon,” says Steven J. Burakoff, MD, the Director of The Tisch Cancer Institute. “His work in combination therapy transformed the way we treat patients. He is really one of the giants.” A past-president of both the American Association for Cancer Research and the American Society of Clinical Oncology, Dr. Holland has received

TEAM

numerous awards from the American Cancer Society, the American Society of Clinical Oncology, and the Leukemia Society of America. In 1972, he was the recipient of an Albert Lasker Clinical Medical Research Award, one of the most respected science prizes in the world. — Anna Horton

SCIENCE

In addition, Drs. Irie and Port are co-principal investigators of a compelling new study, an interdisciplinary collaboration including Champions Oncology. Creating novel animal models bearing the tumor of a patient’s triple-negative breast cancer, the team will evaluate responses to specific chemotherapeutic agents, hoping to “extend the boundaries of current knowledge about triple-negative breast cancer and translate that knowledge into actionable therapeutic strategies.” In triple-negative breast cancer, several major cancer pathways are activated, explains Boris Reva, PhD, Associate Professor of Genetics and Genomic Sciences. “These are well-known pathways, and there are some drugs available or in the process of approval.” The main challenge that scientists face is analyzing and organizing the results of their testing to assign specific drugs that will target these pathways. “We make predictions, and sometimes we feel that this is very exciting. It is big, significant work, but Mount Sinai has a big patient pool, and doctors who can do research from the very beginning to the very end.” “The laboratory component is equally important,” Dr. Schmidt says. As a surgeon, he hopes to pair information about a patient’s response to treatment with the tumor’s different molecular features. “We know that no two tumors are the same, even though they both may be triple-negative breast cancers,” he says. “We will be able to find out how patients respond over time. It’s an investment in the future.” ❉

groundbreaking research and made extraordi-

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Teams of Mount Sinai geneticists and pathologists work together on

NEXT-GENERATION SEQUENCING

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

BY SUSAN KREIMER

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PHOTOGRAPHY BY ANDREW LICHTENSTEIN

Like a Venn diagram, the work of these clinicians and scientists— already considered “a cancer hot spot” that is generating a flurry of excitement—overlaps and intersects, fueled by passion and common goals.


Dr. Carlos Cordon-Cardo, Dr. Nina Longtine, and Dr. Michael Donovan

SCIENCE

ogy, and Director of Experimental Pathology, Biorepository and Pathology Core. “A tumor sample can be identified for the presence or absence of specific mutations to guide therapeutic decision-making.” While still in development, the test panel is already “a cancer hot spot,” Dr. Longtine says, generating a flurry of excitement in the scientific community. “It’s one of the next-generation sequencing tests that people are always talking about. It allows us to look at mutations that are known to be present in cancer across fifty different genes all at the same time. And it can be applied to all different types of cancers.” Previously, scientists would screen for each gene mutation with a separate sequential test. “The ‘multiplexing’ capabilities increase the number of mutations interrogated at less cost and in less time,” she explains. But next-generation sequencing tests are complica ed. A team of experts in diverse scientific and clinical fields must rely on each other—just one person can’t >

TEAM

By working together, we can create something much better for our cancer patients than one of the teams could do alone,” says Nina Longtine, MD, Professor of Pathology and Vice Chair of Molecular Pathology and Genetics. Dr. Longtine is part of a specialized group of pathologists and geneticists who are preparing to launch a promising cancer test panel, which will harness the latest technology to analyze tumors in cancer patients and help determine treatments. In her estimation, this genetic screening tool “is poised to put our patients at the cutting edge of contemporary care.” With the use of similar innovative equipment, scientists from two departments—pathology and genomic sciences—can propel research forward at a swifter pace. Traditionally, geneticists focused on inherited diseases, while pathologists concentrated on blood and tissue diagnostics. More recently, their focal points became complementary. “The idea behind personalized medicine and the focus of this panel is to identify specific DNA alterations, which are known as mutations,” says Michael Donovan, MD, PhD, Professor of Pathol-

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I T ’S ON E OF T H E N E X T-G E N E R AT ION S EQ U E NC I NG T E STS T H AT PEOPL E A R E A LWAYS TA L K I NG A B OU T. I T A L LOWS US TO LO OK AT M U TAT IONS T H AT A R E K NOW N TO B E PR E S E N T I N CA NC E R AC ROS S F I F T Y DI F F E R E N T G E N E S A L L AT T H E SA M E T I M E .” – Dr. Nina Longtine

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

possibly be well-versed in the molecular underpinnings of a disease, innovative technologies and instruments, bioinformatics for interpreting the vast amount of data generated by multiplexed tests, and communication skills necessary to convey laboratory results to physicians and patients. Adhering to the concept that all cancers originate at the DNA level, the test panel searches for biomarkers typically found in cancers of the breast, colon, ovaries, and other organs. Its objective is to identify specific biological pathways altered in the cancer, so that the most appropriate drug or treatment plan can be delivered to a patient. When a patient undergoes a biopsy or resection of a mass, the sample is preserved with a fixative to maintain the architecture of the tissue. A pathologist ensures that the sample is processed properly and examines it carefully under a microscope to identify the tumor cells, Dr. Donovan explains. The DNA extracted from the tumor cells is amplified and screened across the test panel “to evaluate which mutations are present in the tumor,” he says. “It’s fairly straightforward whether the mutation is present or not. The technology is quite sensitive.” In scientific circles, this process is known as Polymerase Chain Reaction (PCR). And in simpler terms, it means amplifying a single molecule one times 10 to the tenth fold— exponentially beyond what the naked human eye can see.

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Such test panel platforms have flexibility, and their applications may be extrapolated to a number of diseases other than cancer in the near future. For instance, Dr. Donovan says, they could help researchers understand the mechanisms behind the plaque buildup that occurs in the arteries and results in cardiovascular disease—a process driven by the proliferation of particular cells. “Our department and institute are really focused on launching personalized medicine and precision medicine for our hospital,” says Daniela Starcevic, PhD, who is an Assistant Professor in Genetics Genomics as well as Pathology and Director of Diagnostic Sequencing. “We provide some essential molecular information as a first step, so the physicians can make better treatment decisions.” For example, in colon cancer, experts are already aware that certain treatments would be ineffective in patients who have carcinomas harboring specific mutations. “We are looking for molecular signatures that will tell us what will work and what won’t work,” Dr. Starcevic says, “so we know up front that putting a particular patient on a specific therapy won’t be successful.” Carlos Cordon-Cardo, MD, PhD, Professor and Chair of Pathology, concurs with this assessment, voicing the Mount Sinai team’s optimism about managing a


DISCOVERER

Dr. Daniela Starcevic (above and top)

TEAM SCIENCE

malignant diagnosis in a more individualized fashion. This is happening, he says, as scientists and clinicians enter a new era of the intersection between pathology and genomics to boost the patient’s possibilities for a cure and a better quality of life. Science is progressing beyond the conventional nature of microscopic evaluation, and Mount Sinai investigators have positioned their team at the forefront of this innovation. New optical microscopes with high-resolution images are enabling Dr. Cordon-Cardo and other researchers to examine alterations of proteins and genes by drilling down to the single cell level and finding the root cause of an affliction. While cancer is the first target of the Mount Sinai team, they hope their joint efforts will lead them to decode the genetic underpinnings of inflammatory bowel disease, neurodegenerative disorders, and other chronic conditions—further extending the concept of Venn overlapping that distinguishes the work of this Sinai team. The results are expected “to have a real translation into the clinic because we can act upon the mutations that are being identified,” says Dr. Cordon-Cardo, who is also Professor of Oncological Sciences and Professor of Genetics and Genomic Sciences. “This is definitely a new paradigm.” ❉

A GROUND-BREAKING HUMAN GENETICIST and pediatrician, Robert J. Desnick, MD, PhD has provided significant and enduring contributions to the field of genetic diseases since he first joined the Mount Sinai faculty in 1977. Dr. Desnick’s research has had a life-changing impact on the lives of patients suffering from a variety of inherited metabolic disorders, particularly those afflicted with Fabry disease. Fabry disease is a rare and underdiagnosed genetic disorder in which a specific enzyme deficiency leads to the storage of lipids in the blood vessels, heart and kidneys; this in turn can lead to renal failure, heart disease, stroke, and early demise. Until 1985 there was only symptomatic treatment for the disease—and then everything changed. Dr. Desnick’s research led to the isolation of the gene and its use to produce the normal enzyme deficient in Fabry patients. His team’s groundbreaking scientific studies provided the rationale for clinical trials of enzyme replacement therapy (ERT) that have conclusively proved effective in treating Fabry disease. Bi-weekly administration of the enzyme (Fabrazyme) corrects the metabolic defect, clears the accumulated lipids, and improves symptoms. This watershed discovery guided the development of ERTs for a broad spectrum of lysosomal storage diseases including Niemann-Pick disease, for which ERT is in clinical trials. In addition to this key work, Dr. Desnick runs the only comprehensive DNA testing laboratory for all of the porphyrias in the Western Hemisphere, and his group started the multi-gene, multi-disorder prenatal carrier screening program, particularly for the prevalent genetic diseases in the Ashkenazi Jewish community. These patented treatments and prenatal screenings now cover some 100 different genetic diseases. “We are proud that our research has led to effective genetic disease prevention and treatment for the many people who suffer from these genetic diseases,” says Dr. Desnick, who has published more than 700 articles, chapters and edited books. “That’s the value of the research.” — Anna Horton

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ON PATROL When the immune system is in good working order, immune cells circulate throughout the body like soldiers on patrol, keeping careful watch for pathogens or other harmful threats and mounting an appropriate response to any danger they detect.

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

BY SARA DANIELS PHOTOGRAPHY BY DON HAMERMAN IMAGES FROM THE LIRA LAB

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A “CT scan” of a T cell being infected by HIV (courtesy of Benjamin K. Chen, MD, PhD)


The intestine is home to a large collection of immune cells and bacteria. Epithelial cells in the intestine (green) separate the immune cells from bacteria.

Tumor cells in the intestine (green) express inflammatory factors (red).

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Sergio Lira, MD, PhD, The Leona M. and Harry B. Helmsley Charitable Trust Professor of Immunology, Professor of Medicine, Clinical Immunology, and Director of the Immunology Institute at the Icahn School of Medicine at Mount Sinai, is the internationally renowned immunologist who has his own eye fixed on the immune system, devoting his career to understanding the complexities of the immune response. “Modern immunology involves three primary areas of investigation: immunodiscovery, immunodiagnostics, and immunotherapy,” Dr. Lira says. “We’re working to understand the pathways in disease processes that involve immune genes so we can improve immunodiagnostic approaches that allow us to identify diseases early on and monitor their progress and response to therapies. And as we reveal important immune targets, we are collaborating with colleagues to develop new drug therapies that will have an impact on these diseases.” Under Dr. Lira’s leadership, the Immunology Institute has assembled a community of nearly 200 scientists, including an elite roster of 40 principal investigators (PI), to power this vision. Collectively, their research explores almost every aspect of immunologic processes: how immune cells are produced, traffic, and communicate among one another and with other cells; how immune cells mount responses to pathogens or cancerous growths; and how the immune system identifies pathogens and “remembers” previous encounters with these organisms. Though their work is perhaps less familiar and accessible to the average person, it holds extraordinary promise for patients living with a wide range of autoimmune and immune-mediated diseases, from the rarest forms of immunodeficiency to the most severe gastrointestinal disorders and allergic reactions, to the most common cancers. Immunologists may just be the unsung heroes of 21st century medicine.

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MNIPRESENT, THE IMMUNE system affects not just one organ or organ system, but all of them. Similarly, its complex network of molecules and cell receptors is not localized to a single area; rather, an immune cell found, say, in the eye may play a role elsewhere in the body. When the immune system is working properly, no one is really thinking about it—except, of course, immunologists, who are as fascinated by the immune system’s normal functioning as they are by its malfunctions. And, of course, as in all systems—even the most brilliantly designed— there is sometimes a glitch. The immune system can overreact—as it does in food allergy and autoimmune diseases such as lupus and multiple sclerosis (MS)—causing immune cells to attack healthy cells in the body without restraint. It can also underreact, as it does when faced with tumors that suppress the immune cell responses so that the immune system doesn’t recognize or attack cancer cells, allowing them to proliferate and spread relatively unchecked. In still other cases, as in primary immunodeficiency, the immune system contains a genetic defect that causes it to make too much or too little of a necessary cell or molecule, leaving the body vulnerable to infection and chronic illness. Like the nervous system, the immune system learns and remembers— yet unlike the hard-wiring that characterizes the nervous system, the immune system is in constant motion, patrolling the body. And

Inflammatory cells (red) invade and destroy the thyroid gland in autoimmune thyroiditis.

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Dr. Andrea Cerutti, Dr. Sergio Lira, and Dr. Charlotte Cunningham-Rundles

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Putting the “Brakes” on Inflammation

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In recent years, immunology has proven to be an increasingly powerful tool for understanding, preventing, and treating a number of human diseases. Indeed, there is a growing body of evidence that inflammation—a natural response of the immune system as it reacts to a physical, chemical, or biologic insult—plays a key role in almost all disease states. Like the immune system itself, inflammation—“an attempt to heal, to restore normalcy to the body,” explains Dr. Lira—can become dysregulated; when it is too intense (acute) or fails to turn off (chronic), inflammation becomes damaging to the very organs it is trying to heal. Indeed, unresolved inflammation contributes to the development of an astonishing array of diseases, including Crohn’s and colitis, cancer, diabetes, cardiovascular disease, asthma and allergies, lupus, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s, among others. “For every immune function, including inflammation, there are built-in controls: something that says ‘go’ and something that says ‘enough,’” says Charlotte Cunningham-Rundles, MD, PhD, David S. Gottesman Professor of Immunology and Director of Mount Sinai’s Immunodeficiency Clinic. “It’s like a brake. If the brake fails, the car can’t stop. Of the more than 200 genes we’ve identified as being involved in immune defects, some of those control the accelerator and others control the brakes.’” Understanding and identifying mechanisms involved in putting the “brakes” on chronic inflammation is thus a crucial aspect of many Immunology Institute investigations, from IBD to cancer. And Dr. Lira, whose own work focuses on the mechanisms controlling inflammatory

cell migration to the tissues and the role of microbiota in inflammation and cancer, leads a team that is among the best equipped in the country to do so. Indeed, Mount Sinai has a powerful institutional understanding of many of the mechanisms underlying inflammation, an expertise dating back to 1932, when Mount Sinai gastroenterologist Burrill B. Crohn, MD first described Crohn’s disease. Drawing on this legacy, Dr. Lira and his team are deploying Mount Sinai’s robust expertise and resources to drive ongoing studies of inflammation and its role in disease in order to discover new inflammatory molecules—and novel therapeutic targets.

The Mechanisms of Teamwork Ask Dr. Lira why teamwork is important to breakthroughs in immunology and you may be met with surprise. And no wonder: As he talks about the many formal and informal configurations that the Immunology Institute’s collaborations can take, it quickly becomes apparent that teamwork is not just important to immunology—it’s inextricable, reflecting the complexity and dynamism of the immune system itself. “Teamwork is crucial to the kind of science that we do,” says Dr. Lira. “We have a very interactive community and we benefit tremendously from this approach. It’s no longer possible for any single person to do this work.” Like the system they study, Mount Sinai’s immunologists transcend traditional organ system-specific boundaries—which means collaborating with colleagues who have complementary expertise is a matter of course.


Immune cells travel through small blood vessels called capillaries.

Moreover, nearly all of the Immunology Institute’s members hold cross-appointments in other departments or institutes throughout Mount Sinai. Core members of Dr. Lira’s team specialize in the intersections between immunology and cancer, food allergy, and IBD, among others. Miriam Merad, MD, PhD, Director of the Human Immunology Center, Assistant Director of the MD/PhD Program, and Professor of Oncological Sciences and Medicine, Hematology and Medical Oncology, is an expert in the development and function of macrophages, cells critical for the inflammatory process, and a leading investigator in the biology of dendritic cells and their potential as a basis for therapeutic cancer vaccines. She also leads Mount Sinai’s immunomonitoring platform, which allows investigators to quickly evaluate the efficacy of a therapeutic intervention by monitoring a patient’s immune response. “We are extremely proud of this effort,” says Dr Lira. “The Immunology Institute is among the first centers in the country offering state-of-theart immune monitoring, a technique that has revolutionary implications for patient care and research.” Hugh Sampson, MD, Kurt Hirschhorn, MD/Children’s Center Foundation Professor of Pediatrics, Director of the Elliot and Roslyn Jaffe Food Allergy Institute, Dean for Translational Biomedical Sciences, and Director and PI of the National Institutes of Health (NIH)-sponsored CTSA program, Conduits, is a world leader in developing novel treatments for the inflammatory conditions associated with allergic responses. Star recruit Andrea Cerutti, PhD, Professor of Medicine, Clinical Immunology, a basic scientist who studies immune responses at the level of mucosal tissues, including the GI tract and the lung, collaborates closely with Dr. Cunningham-Rundles, who has a robust immunodeficiency clinical practice with close to 1,000 patients as well as an active NIH-funded laboratory. “We’re all studying the same molecules,” says Dr. CunninghamRundles. “We have to work as a group.” Synergies abound, uniting these and other immunologists with experts throughout Mount Sinai: Patient blood samples and biopsies from the Department of Surgery are accessed, scored, and diagnosed with the help of pathologists. Clinical immunologists share biological

material from their own patients with colleagues conducting basic science investigations in the laboratory. An antibody made by one lab is shared and examined among several. Immunologists join forces with clinicians, gastroenterologists, cancer researchers, geneticists, computational biologists, and a host of other experts to study a problem through myriad lenses. Scientists gather at monthly meetings and pop across campus—or across the hall—to share ideas, discuss hypotheses, and develop new directions for investigation, ensuring a constant pipeline of translational, patientcentered scientific questions. In the laboratory, immunologists validate the significance of gene targets and attempt to validate the findings identified through the analysis of large gene sets by colleagues in the Icahn Institute for Genomics and Multiscale Biology. Promising targets are explored with the team in the Experimental Therapeutics Institute to identify and develop novel therapeutic interventions.

“We’re very fortunate to be working so closely with investigators who have diverse expertise,” Dr. Lira says. “We’re constantly learning from each other. It’s very exciting.” ❉

A Joint Effort: How the Team Process Works TEAM

Clinical immunologists share biological materials with colleagues.

Immunologists join forces with other scientists to study a problem.

Scientists gather to share ideas and discuss hypotheses.

Findings are vaildated in the laboratory.

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Patient blood samples and biopsies are collected from the Department of Surgery.

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Team: Immunology Teams of experts within the Immunology Institute are joining forces with colleagues across Mount Sinai to take on some of the most promising areas of study, with the greatest potential for life-changing results. Here’s a look at how team science is amplifying efforts to deepen the scientific understanding of immune processes and identify new targets for therapeutic intervention. Inflammatory Bowel Disease

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

With more than 80 years of expertise in Crohn’s disease at its disposal, it is no surprise that the Immunology Institute’s collaborations in inflammatory bowel disease are among its most advanced and productive. Here are three of the most promising projects underway:

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SUCCESS (Sinai Ulcerative Colitis Clinical Experimental and Systems Studies) The team unites the skills and expertise of clinicians and scientists in immunology, genetics, microbiology, and gastroenterology to better understand the biological basis for ulcerative colitis (UC), a form of IBD, and to imagine new pathways to treatment and cure. Together, they are working to identify faulty genes that may contribute to the development of UC and using mouse models to replicate genetic mutations that can help establish whether these mutations make animals more susceptible to disease, how faulty genes may be connected to the microbiome (the ecosystem of microorganisms that reside in the human body), and whether transplanting specific microbiome can have beneficial properties for patients. the team » Dr. Sergio Lira; JeanFrédéric Colombel, MD, PhD, The Leona M. and Harry B. Helmsley Charitable

Trust IBD Center Director and Professor of Medicine, Gastroenterology; Judy Cho, MD, Ward-Coleman Professor of Translational Genetics, and Professor of Genetics and Genomic Sciences and Medicine, Gastroenterology, Associate Chief of Research, and Vice-Chair for Translational Genetics; Jeremiah Faith, PhD, Assistant Professor of Genetics and Genomic Sciences and Medicine, Clinical Immunology; Jose Clemente, PhD, Assistant Professor of Genetics and Genomic Sciences and Medicine; Inga Peter, PhD, Associate Professor, Genetics and Genomic Sciences

Industry Partnership: Icahn School of Medicine & Janssen Biotech Researchers from Mount Sinai’s Icahn Institute for Genomics and Multiscale Biology, Immunology Institute, and Department of Gastroenterology have combined forces with scientists at Janssen Biotech in a first-of-its-kind IBD translational research alliance. The team is drawing on a wide range of investigative tools including fundamental human disease biology, clinical study data, animal models of disease, and robust modeling and data mining. Their goal is twofold: to provide the world’s best understanding of the molecular mechanisms underlying ulcerative colitis and Crohn’s disease, and to advance the discovery and development of next-generation therapeutic solutions. the team » Eric Schadt, PhD, Jean C. and James W. Crystal Professor of Genomics, Director of the Icahn Institute for Genomics and Multiscale Biology,

and Chair of the Department of Genetics and Genomic Sciences; Dr. Sergio Lira; Huabao Xiong, PhD, Associate Professor of Medicine, Clinical Immunology; Stephanie Dahan, PhD, Assistant Professor of Medicine, Clinical Immunology; Dr. Jean-Frédéric Colombel; Carmen Argmann, PhD, Assistant Professor of Genetics and Genomic Sciences

SHARE (Sinai-Helmsley Alliance for Research Excellence) A national, multicenter program supported by The Leona M. and Harry B. Helmsley Charitable Trust and conceived by the late Lloyd Mayer, MD, an internationally renowned immunologist who co-directed the Immunology Institute with Dr. Lira for six years, SHARE unites researchers and research centers from across the country to advance the study and treatment of IBD. Mount Sinai’s team draws on a vast array of multidisciplinary expertise to study the inflammatory components of IBD. the team » Dr. Sergio Lira; Dr. JeanFrédéric Colombel; Bruce Sands, MD, Dr. Burrill B. Crohn Professor of Medicine, Gastroenterology; Dr. Inga Peter; Ashish Atreja, MD, MPH, Assistant Professor of Medicine, Gastroenterology, and Director of Informatics for Research Outcomes and Quality; and Steven Itzkowitz, MD, Professor of Medicine, Gastroenterology, and Director of the Gastroenterology Fellowship Program

Food Allergy Led by Dr. Sampson, the Jaffe Food Allergy Institute is studying the genetics of food allergy and the mechanisms underlying food allergy and how food allergens are processed by the immune system in order to develop novel diagnostic

tests and immunotherapeutic strategies for treating food allergies. Likewise, Dr. Berin’s lab is focused on understanding the mucosal immunology of food allergic disorders and finding methods to modify the allergen-specific T cell response for therapeutic purposes. Dr. Sampson’s team has numerous clinical trials in process, including a trial of an IgE-based vaccine for peanut allergies and another of a compound formulated from traditional Chinese medicine that shows promise for blocking anaphylactic reactions. the team » Dr. Hugh Sampson; Dr. Miriam Merad; Dr. Andrea Cerutti; M. Cecilia Berin, PhD, Associate Professor of Pediatrics

Cancer Co-led by Drs. Miriam Merad and Nina Bhardwaj, the Cancer Immunology and Immunotherapy program is identifying mechanisms of immune dysregulation in the tumor micro-environment and developing a broad spectrum of immune-based interventions that bolster the ability of the body’s immune system to recognize and destroy cancer cells. The study of inflammation plays a key role in the team’s work as well. Dr. Lira is using mouse models to better understand how inflammatory cells and molecules interact in cancer development—and has seen the first examples of highly effective therapeutic intervention using immune molecules that may promote the development of better cancer therapies.


Lymph nodes are collections of immune cells called lymphocytes (green) which traffic through lymphatic vessels (red).

the team » Dr. Sergio Lira; Dr. Miriam Merad; Nina Bhardwaj, MD, PhD, Director of the Cancer Immunology and Immunotherapy Program, WardColeman Professor in Cancer Research, and Professor of Medicine, Hematology and Oncology, and Dermatology; Shu-hsia Chen, PhD, Professor of Oncological Sciences and Surgery; Brian Brown, PhD, Associate Professor of Genetics and Genomic Sciences, Dr. Huabao Xiong; and Julie Blander, PhD, Associate Professor of Medicine, Clinical Immunology, and Director of the Innate Immunity Research Program

Mucosal Immunology Established five years ago and supported by the National Institute for Diabetes and

Digestive and Kidney Diseases, the team is exploring how the mechanisms of mucosal immunology affect the development of the immune response and of inflammatory diseases in the intestine. Together they’re investigating different approaches—using human cells as well as genetically-engineered mouse models—to better understand the function of Th17 cells, which have been proven to be important in the development of IBD and in MS, psoriasis, and other autoimmune diseases, as well as how Th17 cells are made and how they traffic into the gut.

the team » Dr. Sergio Lira; Dr. Julie Blander; Adrian Ting, PhD, Associate Professor of Medicine, Clinical Immunology; Dr. Huabao Xiong; Noam Harpaz, MD, PhD, Professor of Pathology and Medicine, Gastroenterology

Immunodeficiency About 70 percent of all immune deficiencies that have been described relate to antibodies produced by B cells, cells which normally produce protective antibodies. Drs. CunninghamRundles and Cerutti have teamed up to study one such antibody, immunoglobulin A (IgA), which is found in the mucosal surfaces

of the body including the nose, throat, and digestive tract—and which one in 500 people lacks. Together they are exploring big-picture questions: Why is IgA made in such quantities if the immune system can do without it? What might be substituting for it? Sharing data and biological material from Dr. CunninghamRundles’ patients, the team seeks to understand why some patients who lack IgA are relatively healthy, while others suffer. the team » Dr. Charlotte CunninghamRundles; Dr. Andrea Cerutti

LEGENDARY IMMUNOLOGIST

L L O Y D F. M A Y E R , M D

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those that regulate systemic immunity played a crucial role in developing highly effective anti-inflammatory drugs for IBD. In addition to his scientific achievements, Dr. Mayer challenged traditional approaches and championed interdisciplinary collaboration and translational medicine. As a result, he had a major influence on building Mount Sinai’s immunology research enterprise and establishing national and international networks to advance the study of mucosal immunology and IBD. “Lloyd had an uncanny ability to bring people and ideas together,” says Dr. Sergio Lira, who co-directed the Immunology Institute with him. “One of his greatest legacies has been to infuse us with the understanding that collaborating is essential.”

At Mount Sinai, Dr. Mayer helped establish the Immunobiology Center, the nucleus of today’s Immunology Institute. He also recruited many of Mount Sinai’s preeminent immunologists, including Dr. Lira, Dr. Charlotte Cunningham-Rundles, and Dr. Hugh Sampson— all of whom are now world leaders in their own right—and was a passionate mentor and educator to generations of young physicianscientists. “Lloyd led by example and friendship,” says Dr. Lira. “Whether for patients, first-year medical students, or practicing clinicians, he always had a way of making complex material accessible.” Dr. Mayer also played a key role in creating the Helmsley Inflammatory Bowel Disease Center and establishing the Sinai-Helmsley Alliance for Research Excellence (SHARE), a national network of seven academic medical centers dedicated to leading-edge IBD research, led by Mount Sinai and supported by The Leona M. and Harry B. Helmsley Charitable Trust. “He was an extremely generous person, a rare person,” says Dr. Lira. “Our whole community loved and misses him dearly.” ❉

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FEW HAVE HAD SUCH AN INDELIBLE impact on the study of immunology and inflammatory bowel disease (IBD)—at Mount Sinai, especially—as the late Lloyd F. Mayer, MD. “Lloyd was a pioneering clinical immunologist and gastroenterologist whose fierce intelligence and deep empathy made him equally beloved by patients, colleagues, students, and trainees,” notes Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean. Dr. Mayer was a pillar of Mount Sinai’s immunology program for more than 30 years. Until his death in September 2013, he served as the Dorothy and David Merksamer Professor of Medicine, Chief of the Division of Clinical Immunology, and Co-Director of the Immunology Institute; and he led an internationally renowned and National Institutes of Health-funded laboratory that focused on mucosal immunoregulation, IBD, and cytokine regulation of human B-cell differentiation. An insightful and groundbreaking investigator, Dr. Mayer dramatically advanced our understanding of primary immunodeficiency disease and IBD; his team’s discovery that the epithelial lining cells of the intestine are active regulators of mucosal immune responses distinct from

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GOING

DEEP

How teams from a wide range of disciplines

are tackling heart disease together at Mount Sinai

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

BY KAT IE Q UACK E N BUSH SPIEGE L

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PHOTOGRAPHY BY ANDREW LICHTENSTEIN

HE HEART IS THE STRONGEST AND MOST COMPLEX muscle in the human body, pumping blood with just the right amount of force and at the right tempo. Put your head on someone’s chest and you can hear its perpetual, unique sound. It never rests. But sometimes the heart weakens and can’t pump blood as hard, as far, or as well: heart failure. Usually, this occurs in older people with complicating health issues, such as coronary artery disease or uncontrolled diabetes; in some otherwise healthy families, a specific genetic mutation also causes heart failure. Heart failure is a slow, progressive disease but—with no known cure— within 10 years of a diagnosis, only a quarter of patients are still alive. More than 6 million Americans have heart failure today. ➔


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MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Dr. Roger Hajjar ( in jacket and tie) with members of the Heart Team (clockwise from lower left): Drs. Francesca Stillitano and Ludovic Benard; Drs. Martin Schwarz and Changwon Kho; Drs. Sima Tarzami, Kevin Costa, Jason Kovacic, Kenneth Fish, Djamel Lebeche, Fadi Akar, and Thomas Weber; Drs. Ahyoung Lee and Changwon Kho

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Under the direction of Roger Hajjar, MD, Director of the Cardiovascular Research Center and The Helmsley Moelcular Research Center and the Arthur and Janet C. Ross Professor of Medicine, teams of experts in a wide range of scientific fields—tissue engineering, gene therapy, stem cells, cardiology, electrophysiology, and molecular engineering, to name a few— are coming together to go deep with heart failure. Like special teams within a football squad, these talented groups are bringing leading-edge consulting and expertise to develop and test new therapeutic approaches to tackle this deadly condition. “You can imagine this is a multidisciplinary effort; this is not something any of us could do on our own,” says Kevin Costa, PhD, Director of Cardiovascular Cell and Tissue Engineering and Assistant Professor of Medicine, Cardiology, whose lab collaborates on Dr. Hajjar’s heart failure effort. “But Mount Sinai has an environment where you can be immersed and work together to understand the important diseases, like heart failure, use the new therapies being developed, and have direct access to things like gene therapy and stem cell engineering. It’s different here, and it’s genuine.”

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HEY SAY PRACTICE MAKES PERFECT. “There are families with mutations in a specific protein that cycles calcium, which is necessary for the heart to work,” says Dr. Hajjar, who is also Professor of Gene and Cell Medicine and Director of the Cardiology Fellowship Program. “Patients with these mutations develop overt heart failure, and die from sudden death.” Dr. Hajjar and his team are using these families and their genetic mutation to study that result, with the goal of developing new therapies that work for all patients with heart failure. Here is a simplified version of their game plan: The team worked with the affected families to obtain skin samples. Together with the team in Mount Sinai’s stem cell core, Dr. Hajjar and his researchers have used the samples to generate induced pluripotent stem cells (IPSCs), which are exact replicas of each participating patient’s own stem cells; they can be used to grow any type of cell in their body—including heart


 You can imagine this is a multidisciplinary effort; this is not something any of us could do on our own.” – DR. KEVIN COSTA

Dr. Hajjar, like some of his colleagues, has successfully completed clinical trials and has launched companies to bring this type of idea to patients. He says that this expertise with developing intellectual property, together with Mount Sinai’s infrastructure (including rich experience in developing animal models, the technology to screen potential drug compounds and validate them) is the team’s power play. “If you go to a drug company and say, ‘We have an interesting target, but you guys have to find the drug and develop everything,’ it’s not going to be the company’s biggest priority regardless of how promising the target is,” says Dr. Hajjar. “The fact that we can work together, as a team, at Mount Sinai means we can go to drug companies and say, ‘We have one molecule, we know where it is, what it does, how to screen for it, and we already did the pre-clinical screening,’ The risks go down for the company and they’re interested—or you can start your own company. At Mount Sinai, we work together, in teams, to advance our therapeutic approach to deal with things like heart failure.” And because Mount Sinai is a medical school embedded in a hospital, patient care—and actual heart failure patients—are at the center of every scientific effort, no matter how deep the research goes. “Very basic science is important, but we have a translational, therapeutic focus; this is really the blood of the institution,” Dr. Hajjar says. “My team here is always looking for cutting-edge technologies, cuttingedge science, to be incorporated into our work because we want patients to benefit from it.” ❉

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Near infrared imaging during gene vector delivery

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Dr. Changwon Kho (top); Dr. Kevin Costa (bottom)

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muscle cells that bear the exact genetic mutation that caused the family member’s heart failure. Dr. Hajjar’s team then turns to Dr. Costa and his tissue engineering group, who, in a dramatic improvement over muscle heart tissue cells in a Petri dish, can actually build a 3-D replica of the heart muscle cells that beat and pulse exactly as heart muscle cells should—and with the specific genetic mutation that causes heart failure in each individual patient. “We’re using these engineered tissues as screening tools to see if Dr. Hajjar’s new gene therapy delivery method is going to be effective,” says Dr. Costa. “It’s nifty that you can grow cells in 3-D, but this is also fundamentally different biology than cells in a Petri dish and they better predict whether or not a given therapy will work in humans.” Dr. Hajjar’s new gene therapy method harnesses the power of a particular gene, called stem cell factor, which seems to have the unique ability to attract other healing stem cells circulating in the body to home to damaged locations in the heart muscle and begin to repair it. To create a therapy, Dr. Hajjar and his team have tried using a virus bearing the gene therapy injected into the diseased heart. This viral vector technique, which, with the help of scientists in Mount Sinai’s Translational and Molecular Imaging Institute, can be visualized as it is injected, proved to be very effective at delivering the gene therapy. However, it couldn’t be “turned off”: The healing stem cells wouldn’t stop homing to the damaged locations, even after the problem areas in the heart muscle were healed. Time for a different play. Now, together with Changwon Kho, PhD, of the Cardiovascular Research Center, Dr. Hajjar and his team are using a nanoparticle which allows them to create a sort of “time-release” version of the stem cell factor gene therapy. “Our results indicate that this pathway may be a new therapeutic target at the earliest signs of heart failure development,” says Dr. Kho. “It may be beneficial in preventing its progression, which is a much-needed advance for the millions suffering from heart failure.”

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CELLULAR

DREAM TEAM CONSIDER STEM CELLS THE ULTIMATE TEAM PLAYERS. BY K AT IE Q UACKENBUSH SPIEGEL

PHOTOGRAPHY BY DON HAMERMAN

In the human body, our stem cells have the unique ability to differentiate into specialized cells and divide to produce more stem cells. Stem cells recruit each other—or even create more of themselves, their own perfect cellular “teammates”— to tackle a given problem within the body, whether it’s repairing damage caused by disease or injury or building new

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

tissue. They are the cellular dream team. And at Mount Sinai, they’re in the hands of a different kind of dream team.

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The scientists working in the Induced Pluripotent Stem Cell Core, under the leadership of Ihor Lemischka, PhD, Director of The Black Family Stem Cell Institute, Lillian and Henry M. Stratton Professorial Chair of Gene and Cell Medicine, are harnessing the power of stem cells and building teams of stem cells in revolutionary new ways. These researchers are also forming exciting partnerships with disease-focused and genomic medicine teams at Mount Sinai to deliver new strategies for tackling tough diseases and conditions. One novel technique being employed by the stem cell team sounds kind of like science fiction. “We take a patient’s own skin cells, and introduce several gene products that turn on and off groups of genes,” says Dr. Lemischka, who is also Professor of Development and Regenerative Biology and Pharmacology and Systems Therapeutics. This kick-starts the process of cell population, where cells begin to

reproduce. The combination begins to generate a type of cell called hematapoetic stem cells—the kind of stem cells that, ultimately, can make all the cells in the blood. Dr. Lemischka says his team is currently in the process of publishing an article about this groundbreaking work. “For patients, we can basically take a skin sample and make cells that can be used in lieu of, say, a bone marrow transplant. It can be hard to find a bone marrow donor sometimes, particularly for minority populations, and this way we can grow a patient’s own bone marrow cells to transplant.” The stem cell team is also partnering with Mount Sinai’s Icahn Institute for Genomics and Multiscale Biology—a pioneering collaboration between two leading-edge scientific groups—to make stem cells for a cohort of 300 patients with insulin resistance. Together, the team is completing deep


genomic sequencing for those cells, which is exciting news problems, distinct physical characteristics, and, sometimes, for the millions of Americans struggling to control their diabetes leukemia. with existing therapies. “In Li-Fraumeni syndrome, we’ve been able to make induced “Our teams are looking at fat and vascular cells from these stem pluripotent stem cells from one affected family and successfully cells. The idea is that we will be able to model the insulin resistant model many of the features of the osteosarcoma, a bone cancer, condition, and then correlate it with global gene expression that members of the family have had,” says Dr. Lemischka. profiles from these stem cells,” says Dr. Lemischka. In Noonan syndrome, some mutations predispose patients He says that the teams have already colto juvenile myelogenous leukemia, while othlected samples, generated patient-specific stem ers do not. “With Bruce Gelb’s lab, we’ve been The collaboration, cells, and generated genomic profiles for 100 able to recapitulate some of the features of this collegiality, and study participants. “It’s quite an ambitious leukemia in vitro with induced pluripotent multidisciplinary project, but it’s potentially quite significant; our stem cells,” says Dr. Lemischka. goal is to develop platforms for patient-specific Unlimited opportunities to team up interactions are very diabetes drug discovery.” with a diverse range of disciplines on impormuch part of the The stem cell team is also working with tant medical problems is rare, Dr. Lemischka Bruce Gelb, MD, Director of The Mindich Child says, but it is one of the characteristics that culture at Mount Sinai. Health and Development Institute, Director Mount Sinai is renowned for. He says this – DR. IHOR LEMISCHKA of the Center for Molecular Cardiology, and commitment to teamwork drew him, and Professor of Genetics and Genomic Sciences and Pediatrics, the scientists working in his lab, away from peer institutions Cardiology, and his research team. Together, the groups are and industry. tackling two genetic diseases that affect children: Li-Fraumeni “The collaboration, collegiality, and multidisciplinary syndrome, a rare disorder that greatly increases the risk of young interactions are very much part of the culture at Mount Sinai,” patients’ developing several types of “old-age” cancer early in he says. “It’s the main reason I really enjoy being here, and life, and Noonan syndrome, a relatively common genetic disorder why I think stem cell science—and my own work—is more that results in problems such as congenital heart defects, learning productive than it’s ever been before.” ❉

Dr. Lemischka and his team

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WHEN PIGS FLY Mount Sinai’s Peter Palese, PhD and Adolfo García-Sastre, PhD are collaborating with scientists around the world to study influenza pandemics while they develop a “universal” flu vaccine BY K ATI E Q UACKEN BUSH SP I EGEL

EVERY YEAR, THE INFLUENZA VACCINE FIGHTS A TOUGH fight. It has to be configured to the previous year’s viruses, and some years there is not enough to go around. And for a variety of reasons—mainly based on erroneous information—some of us submit to the seasonal vaccinations only with misgivings, or even refuse altogether to be vaccinated. But getting a flu vaccine, most health professionals agree, is an important civic duty that promotes public health, while also helping us avoiding the miseries of seasonal flu infection for the year. If we skip the vaccine and come down with the flu, there is a chance of developing severe complications, even though we have some built-in natural immunity since similar strains of seasonal virus circulate every year and, inevitably, we have been exposed in our past. To complicate matters, the flu vaccine doesn’t always match circulating flu viruses; when this is the case, vaccine efficacy is greatly diminished. Take a look at the swine flu pandemic of 2009, or at the alarming bird flu headlines that pop up in the news from time to time: These are vivid reminders of what’s at stake when animal strains of influenza take novel, perhaps lethal forms that pose a new kind of threat

P H OTOGRA P H Y BY DON H A M ERM A N

to humans, and which current flu vaccines do not match. While physicians have tools to control seasonal influenza infection, animal flu viruses, like swine flu and avian flu—that somehow jump from their animal hosts into humans—remain unpredictable threats. “It’s impossible to predict which is going to be the next pandemic virus, and it’s impossible to predict when it’s going to happen,” says Adolfo García-Sastre, PhD, Director of the Global Health and Emerging Pathogens Institute and Professor of Microbiology and Medicine, Infectious Diseases at the Icahn Schoolof Medicine at Mount Sinai. “There are flu strains that started and are circulating in nature in different hosts—a bird, a pig, a horse—and they usually don’t jump into humans. But when they do, if they transmit well from human to human, we have no immunity against them— and this is when we see a pandemic.” Such pandemic viruses originate every 10 to 40 years—evidence has emerged that indicates the 2009 swine flu was a virus related to the deadly flu pandemic of 1918—and are worrisome to the medical community, to governments, and to the global community: Exactly how animal viruses are transmitted to humans is not fully understood and, currently, there are no vaccines to prevent them. Fortunately, Dr. García-Sastre and Peter Palese, PhD, Chair of Microbiology at Mount Sinai, are working together on a multi-year, multi-disciplinary, multi-institutional project. Talk

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Animal flu viruses— that somehow jump from their animal hosts into humans—are the cause of the flu pandemics that take the biggest toll on humans.

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Dr. Peter Palese, PhD (left) and Dr. Adolfo Garcia-Sastre (right)

“A universal flu vaccine would replace annual vaccination, and would be given to a patient every twenty years, or maybe even once, for lifetime protection against all influenza strains.”– Dr. Peter Palese

about teamwork: the two investigators have been collaboratively tackling influenza in the laboratory since Dr. García-Sastre started as a junior researcher in Dr. Palese’s lab more than two decades ago. And just this spring, Dr. García-Sastre was named one of the principal investigators for an inter-institutional, international collaboration funded through a multimillion-dollar contract with the National Institutes of Health that drives explorations into why and how this happens, starting at the molecular level. The effort, called the Centers of Excellence for Influenza Research and Surveillance (CEIRS), involves the participation of multiple research institutions and the collection of flu viruses through swabs from animals around the planet, from Argentina to Australia to Japan, and the study of their properties. “It is still unclear what makes a virus transmissible for humans—that is one of the Holy Grail questions in influenza,” says Dr. García-Sastre. “That’s what we’re trying to accomplish with our research. We want to figure out why particular strains are transmissible for a particular host, why others are not, and then use that to come up with better ways to help prevent animal influenza from becoming transmissible in humans.” Mount Sinai’s participation in the effort, through the Center for Research on Influenza Pathogenesis, contributes the collaborative work of some of the greatest minds in biomedicine, including Mount Sinai’s experts in genomics, epidemiology,

virology, pathology, ecology, bioinformatics, biostatistics, molecular biology, and in animal models, among others. But, Dr. García-Sastre says, once they figure out how a pandemic starts, the Mount Sinai team is going to keep going, and figure out how to prevent its happening in the first place. “There are two ways to prevent pandemics: one is to understand how they originate, which we are studying with CEIRS,” says Dr. García-Sastre. “The other way is to come up with vaccines that will cover not only seasonal flu strains, but also any other potential strain that exists in nature, something we call universal vaccines.” The laboratories of Dr. Palese and Dr. García-Sastre are collaborating to develop a universal flu vaccine that would not only cover the usual seasonal strains, but also any pandemic strains that might crop up in the future. For example, it would protect against equine influenza, which currently only occurs in horses, if somehow the virus passed into humans and began circulating. “A universal flu vaccine would replace annual vaccination, and would be given to a patient every twenty years, or maybe even once, for lifetime protection against all influenza strains. It would also be a more effective vaccine than what we have right now,” says Dr. Palese. “This is a very important collaborative effort and is a good example of how we can muster different laboratories in a collaborative effort to achieve a major breakthrough. “Something that is fostered here at Mount Sinai is an awareness that one cannot really achieve breakthroughs alone anymore.” ❉

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DIALOGUE

TEAM STEPHANIE TEAM PHOTOGRAPHY BY JAMES NUBILE AND GONZALO VILLOTA

In June 2013, Stephanie Lee (right) received a diagnosis of stage 4 metastatic colon cancer from her Mississippi hospital. That was the beginning of a story that brought together “Team Stephanie”: Journalists Tom Junod and

Mark Warren wrote about her in Esquire, connecting her with Mount Sinai scientists and physicians who are moving into uncharted waters to save her life. Earlier this year, a panel held in Palm Beach, Florida brought Ms. Lee,

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Mr. Warren, and Mr. Junod face-to-face with some of the doctors on her case:

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Eric Schadt, PhD and Ross Cagan, PhD, who are combining their unrivalled expertise, leveraging Big Data, genomics, and bioscience breakthroughs to identify uniquely personalized treatments for her cancer; Daniel Labow, MD, whose surgical insights into Ms. Lee’s case are defining the new parameters of her care; and Kenneth L. Davis, MD, Mount Sinai’s CEO and President, whose encouragement of innovation set the stage for this novel work.


E

TEAM

SCIENCE

45


Stephanie meets the fly: Flanked by Mark Warren (far left) and Tom Junod, Ross Cagan introduces Stephanie Lee to “the Stephanie Fly.”

Tom Junod: Stephanie, we’re here today to talk about personalized cancer treatment. When you received your diagnosis, did it feel in any way personalized? Stephanie Lee: I didn’t feel any compassion, hope, or love when I received my diagnosis—I felt like I’d been cut with a knife, and when you get cut with that knife you feel like you’re alone, you’re separate. Dealing with cancer is like you’re in prison. You’re limited in what you can do and it’s scary, so scary. Junod: When you asked the doctor in Mississippi what your diagnosis was and how much time you had, he gave you, I believe, a statistic. Lee: He said six months if the chemotherapy didn’t work and between twenty-four and twenty-eight months if the chemotherapy worked.

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Junod: Dr. Labow, Stephanie is receiving the standard of care from her facility; can you explain to us what that entails?

46

Daniel Labow: The avenues we can take to control this disease are very different in different people. I feel the standard of care is to look at each case individually and use all of the different aspects of care and apply them when appropriate to the patient. Cancer care has to be multi-disciplinary; genomics is now part of that multi-disciplinary care, in addition to surgery,

chemotherapy, and radiation. If you look at a line in a textbook, and you read “stage four colon cancer,” then chemotherapy is the standard of care. But when we looked at the data, clearly employing surgery, chemotherapy, and—in parallel—all these other avenues are what I would call the standard of care for treatment for Stephanie. Junod: So even in the current standard of care, there is some room for personalization. Labow: Absolutely. I think personalizing care and truly tailoring it towards the patient is standard when it comes to cancer. Junod: Dr. Schadt, how is big data helpful in personalizing care? Dr. Schadt: Think about this: During every lap around the Indianapolis 500 racetrack, they’re collecting three gigabytes of data to monitor every aspect of each of those cars. In the America’s Cup, Oracle’s boat collects 300 gigabytes every single day. They’re dropping servers off the boat into the water so that other boats can take those servers and analyze the data to really understand what’s going on in that boat. Now take a look at what happens to a newborn. Medical centers collect maybe ten to twenty variables of information on this very complex living being, not even a minor fraction of what is collected on a race car or a big sailing

boat. But technology has now enabled us to take the same kinds of snapshots used on race cars and boats—on people. Our aim is to acquire all that information for Stephanie’s tumor. What’s going on in the normal cells of Stephanie’s body? All the different genes that are in play, how are they interconnected? What’s being disrupted? How is that changing over time? Just like the Indy race cars, we can apply high-end analytics to that monster amount of information to better diagnose and treat. So if we use all of the big data we can generate on individuals and identify specifically in each individual what’s actually going on—here

“The problem with cancer is that everybody is trying to simplify a complex problem. But I embrace complexity.” – Dr. Ross Cagan


Why fruit flies?

are the pathways that are disrupted and here are the different types of drugs that can target those pathways—then we can tune the treatment to the given individual. Junod: Mark, tell us how you heard from Stephanie.

Junod: I was actually writing a story about Google and I went down to see Eric because he is a one-man social network. I mentioned to him that there was somebody I had written about in the past whom I cared about and that she had a terminal diagnosis for colon cancer. And Eric looked at me and said, “That’s exactly the kind of patient we take.” It was an electric moment because I could see these two worlds and the possibility of them colliding for the good. Shortly after that, Stephanie received a phone call.

Schadt: We immediately started to coordinate our work with Stephanie’s care provider, getting tissue and blood samples so that we could

SCIENCE

Lee: Eric called me and told me I’d been accepted into the program. I was ecstatic—I felt honored. It put life back into me.

“They allow us to capture the complexity of the patient’s tumor—as identified by Eric Schadt’s team—in the context of a whole animal. We can screen them readily, quickly, and cheaply; they’re very good at making more of themselves. We use the fly as a surrogate for the patient, looking for drugs that work, and then come back to the patient with those drugs, for treatment. Each patient’s tumor is truly different from any other—and the fly allows us to capture all of that.” – Dr. Ross Cagan

TEAM

Mark Warren: On May 7th Stephanie wrote me a Facebook note out of the blue saying, “Mark, I found out today I have colon cancer, have to go for surgery, please keep me in your prayers.” So we began to correspond. Within a couple of weeks we had begun to talk and much to my surprise, and very irregular in journalism, we were talking every day. I had already begun to hear the despair in her voice about the darkness that she felt she was being cloaked in, how she wasn’t being given options. Fairly quickly, within about five weeks, her diagnosis went from bad to worse because her cancer had metastasized to her liver. June 17th was the day she was told she was going to die. A few days

later, Tom, you came to New York to interview Eric Schadt for a different story. And it was your idea to talk to Eric about Stephanie.

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understand her tumor and her germ line—what DNA was she born with. Then we did a wholegenome sequence, including her RNA, the active components of the DNA. Our supercomputers help us generate all of that information and then interpret it. And then we handed it off to Ross Cagan to do his magic. Ross Cagan: The problem with cancer is that everybody is trying to simplify a complex problem. But I embrace complexity—in this sense, Eric and I are really parallel thinkers. And I had a system that could embrace complexity, could embrace Stephanie’s complexity—and that is the fruit fly. My lab has spent the last year working with Eric and his team. In fact, we have weekly meetings, every Wednesday morning; it’s the most amazing meeting you can imagine, where we all get together and we put our various styles of thinking together. We can now build a fruit fly that embraces the genetic complexity of

Stephanie. This doesn’t have one little mutation in it; instead, our fly reflects the multiple mutations her cancer contains and encompasses everything we can find in the tumor that’s wrong with it. Then we start applying novel drug combinations to the fly; the individual drugs are FDA approved but most combinations haven’t been used before for cancer. And just to be clear on this, I could not do this elsewhere and I absolutely couldn’t do this without Eric and the big data. Junod: When you think of academic researchers, you think of massive egos, of turf battles, but that did not happen. Dr. Davis, is that typical of academic researchers? Davis: The reality is that competition in science happens all the time, but with the right values and good people and with the right goals in mind, you can put competitive thoughts aside. And in this case these people were able to do that because it was for a greater good. The

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Top, left to right: Dr. Kenneth Davis, Tom Junod, Dr. Eric Schadt, Stephanie Lee. Insets: Tom Junod, Dr. Daniel Labow, Stephanie Lee, Mark Warren; Dr. Daniel Labow

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brilliance of your article in Esquire is that it points out the rewards for this collaboration. Schadt: Individual efforts are the old way and just not how, in my view, the medicine of the future is going to operate and be successful. Mount Sinai is really a breath of fresh air, one of the few places that encourage this sort of cross-disciplinary, integrative approach. Junod: I don’t think that anything demonstrates that as much as Stephanie’s reception when she traveled from Ocean Springs, Mississippi to New York City. You met Dr. Labow and he said something very different from what your doctors had said. Lee: He said a doctor has to have the imagination to see past the impossible. And that just changed my whole outlook on everything. If you can see past the impossible, anything is possible in my book. That was a world-changer for me.


“If you can see past the impossible, anything is possible in my book.” – Stephanie Lee Warren: Stephanie was due to have surgery on her liver in a week and she didn’t know if it was even a good idea, if it was even advisable. She came away from her meeting with Dr. Labow knowing from one of the great experts in the country that the chemotherapy had presented the opportunity for surgery—and it changed her entire outlook. Then in the afternoon we went to Eric’s lab, which is like traveling to a different century in the future—a part of the lab that they called Greenland, because all the cubicles are green. The brain power assembled in Greenland is probably unprecedented. Eric said, “Come over here, I want you to meet the guys who did the deep analysis on your data, Stephanie.” Then he said, “Hey guys, I would like you to meet Stephanie Lee.” Up till then, she had been only a mass of data to them. But the seventy-three mutations that they had detected in her data, that worked in network to cause her cancer, had just walked into the room. And one of them, Andrew, stood up slowly, clutching her hands and he was speechless. He could only say, “You’re the person. You’re the person.” His eyes filled with tears. I’ve been doing this for twenty-five years, and I’ve never experienced such a moment in my life. The nexus of the science and the human being was so profoundly demonstrated in that moment. Afterwards, we walked up Madison Avenue, not saying much to each other, and finally I stopped and said, “Stephanie, what do you think?” And she said, “I think I’m going to live.” The hope that this process has given her, no drug conceived by man can produce—it’s because of the presumption to see past the impossible.

Labow: You know, we hear about the press—the negative, the positive—but this would not have started without your out-of-the-box thinking.

Junod: What really needs to happen for personalized cancer treatment to become the standard of care?

Junod: Dr. Labow, tell us about the next steps with the Tumor Board.

Schadt: One important thing on the clinical side is to make sure that everyone taking care of a patient thinks that way and understands what options are there.

Labow: We invited Ross and Eric to come present their data, and we discussed Stephanie’s case in the traditional clinical sense, thinking innovatively and imaginatively as to how we could operate on the liver and thinking about the different modalities we could apply—surgery, chemotherapy—depending on where the tumors were. In fact, it was a wonderful marriage of science and clinical care; one without the other would not be successful. It was so simple, yet so profound: We could give the science time by following the traditional standard of care. Cagan: Eric and I had no idea what to expect when we walked into the Tumor Board meeting— Labow: —at seven AM! Cagan: They didn’t just listen to what we had to say; they embraced our suggestions and actually were quite excited about what we were presenting to them. This really was a first, at least in my world.

Davis: It’s important to keep in mind that what you’re looking at is the future. But we must also understand that the revolution in genomics has spawned a lot of false hopes. You can have your genome sequenced and think that’s going to tell you everything you need to know. But what Eric is telling you is that’s not anything close to what you need to know. You need to know your DNA, your RNA, some of the proteins—it’s a very complex business. So what we’ve all got to do is get behind science, get the NIH to be funded adequately, so that we can begin to make these advances on a nationwide level. What we do can become standard of care around the country in ten years. But there’s a horrible paradox: The opportunities are enormous—yet the question is, does the country have the will, have the direction? We’ve got to rally our Congressmen and Senators to understand that to take advantage of this revolution, we have to put our foot on the gas. This is no time for retrenchment. ❉ As of publication, Stephanie Lee had completed her standard of care treatment; Stephanie Fly 2.0 was nearing completion.

Ross Cagan, PhD is Associate Dean of the Graduate School of Biomedical Sciences, and Director of the Center for Personalized Cancer Therapeutics.

Daniel Labow, MD is Chief of the Surgical Oncology Division and Co-Chair of the Gastroenterology Disease Management Team.

Mark Warren is Executive Editor of Esquire, where he has worked since 1988, directing much of the political writing.

Kenneth L. Davis, MD is CEO and President of the Mount Sinai Health System.

Stephanie Lee is an Iraq War widow who has been diagnosed with stage 4 colon cancer.

Tom Junod has been a writer at large for Esquire since 1997 and the recipient of two National Magazine Awards from the American Society of Magazine Editors.

Eric Schadt, PhD is Jean C. and James W. Crystal Professor of Genomics and Director of the Icahn Institute for Genomics and Multiscale Biology.

TEAM

Labow: It’s really the epitome of how great care means putting all the different pieces together.

THE PARTICIPANTS

SCIENCE

To  view video excerpts of the panel, and to read the original “Patient Zero” article, visit philanthropy.mountsinai.org

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Gv

GIVING Exploring Success: Campaign Q&A areas of research were added. That kind of dedication was at the heart of our success. Other key differences: Our President, Ken Davis, and Dean, Dennis Charney, embraced the plan with an equal amount of passion—and they inspired our Trustees with a bold vision. As a result, our Trustees contributed at an unprecedented level. Trustee involvement was markedly different from most other institutions: A board might be expected to provide fifteen to twenty percent of the total campaign; our Trustees provided nearly fifty percent. Q: What does that level of support indicate about an institution? A: It speaks to the Trustees’ faith and confidence in the leadership. It also speaks to the extraordinary commitment by our Board Chair, Peter May. Q: What was the biggest challenge for the Campaign for Mount Sinai?

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Mark Kostegan, FAHP, Mount Sinai’s Chief Development Officer and Senior Vice President for Development, weighs in on the completed Campaign for Mount Sinai—and why an international economic disaster can actually be helpful to philanthropy.

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A: It was the timing of the Campaign. It was conceived in 2007; I arrived early in 2008—on the threshold of the Great Recession. Launching a campaign in a city as hard-hit as New York was especially challenging. However, the Trustees were committed to its success. We had to take a step back—a giant step back—from asking for most large gifts, but we used that time to deepen our Board’s understanding of the strategic plan and its potential impact. We spent time discovering what aspect of our plan was most relevant to the

Q: You have a distinguished history of directing

interests of each Trustee. Our hope and our expectation

successful campaigns in the health care field.

was that when the economy got better, we would be in

How did this one differ?

a better position to make a strong case for support for

A: We had a well-defined strategic plan that specifi-

an area that resonated with a donor.

cally mapped what was needed for success. The President, the Dean, and our Trustee leadership

Q: But the economy took a while to recover.

stayed true to that plan. In fact, it became even more

A: It did, so there was an ongoing level of uncertainty

powerful over the campaign years as new, compelling

as we moved forward. Many campaigns elsewhere were


put on hold or delayed. We persevered. In many ways,

Q: What is the philosophy that

we can be especially proud of our accomplishment

guides you as a development

because of the period of uncertainty in which it was

officer, and that you

conducted. In 2009, few would have thought that we

believe drives a successful

would achieve $1.5 billion against our $1 billion goal.

fundraising team? A: It is the importance of being

Q: Who were some of the pivotal players

donor-centric. You need to listen

in the Campaign?

to what each donor and their

A: Individual Trustees did so much to ensure that we

family wants to accomplish. This

kept the momentum going. The Campaign Steering

takes patience and persistence.

Committee—led by Jim Tisch—really “got it” and

We need to be tolerant of the

helped to educate others. Rich Friedman was also a

ambiguity that often surrounds

key member of that committee. He is a great example

the timing of a gift. A successful

of a volunteer leader who took the time to find an

team is one that is stimulated

area that he and wife, Susan, and their family could

by a mission, competitive, and

devote their time and resources to. The result was

stubbornly devoted to achieving a

the creation of The Friedman Brain Institute. I also

goal. It is a team that is informed

have to mention Fred Klingenstein, a true philan-

by metrics, but not paralyzed by

thropist. Fred saw that the recession was a potential

them. And one that finds real

game-changer for our Campaign, and he gave what

enjoyment in this work.

was at that point the largest gift ever made to Mount Sinai. Fred just wanted to make it all happen, and his

Q: What’s next?

commitment energized the Campaign.

A: Mount Sinai is now a large health care system. In the months ahead, a strategic plan will be

Mark Kostegan and Dr. Elisa Port

formulated that will define the direction of the System. Just as philanthropy efforts were guided by the strategic plan during our campaign, so, too, will the new plan guide us again. I can’t wait

CAMPAIGN BY-THE-NUMBERS

$1.5 billion RAISED

38,500

CAMPAIGN DONORS

29,620

FIRST-TIME MOUNT SINAI DONORS

215

GIFTS OF $1 MILLION +

275+

NEW RECRUITS BY 2015

21

STRATEGIC INSTITUTES LAUNCHED

$82 million+

ADDED TO RESEARCH BUDGET

500,000+ sq ft

IN LEON AND NORMA HESS CENTER FOR SCIENCE AND MEDICINE

to see what unfolds.

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Gv

GIVING

Celebrations Over the past year, Mount Sinai has held 40 events in New York City, the Hamptons, Florida, and at the Aspen Ideas Festival, attended by nearly 6,000 guests. Here is a look at some that celebrated our community of dedicated, committed partners.

1

Dubin Breast Center Fact vs. Fiction Luncheon and Symposium WHEN: September 30, 2013 WHERE: 320 Park Avenue WHO: 1. Eva Andersson-Dubin, MD, Trustee; Cynthia Besteman, Elisa Port, MD, FACS, Karen Adelson, MD, Sheryl Green, MD, Phillip Landrigan, MD, MSc, Guy Montgomery, MD, Laurie Margolies, MD, Carlin Vickery, MD, Perri Peltz Ruttenberg. 2. Woodson Merrell, MD, Chair, Department of Integrative Medicine, Mount Sinai Beth Israel. 3. Caryn Zucker, Perri Peltz Ruttenberg, Carolyn Schenker. 4. Vivian Fisher, Nina Wexler, Laura DeMare. 5. Jana Happel and guests. 6. Gabrielle Beacon, Chris Mack, Lisa Evans, Susan Kessler.

For more about the panel, visit philanthropy.mountsinai.org.

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5

2

3

6


1

2

3

Dubin Breast Center Third Annual Gala WHEN: December 9, 2013 WHERE: Mandarin Oriental WHO: 1. Curtis Schenker and Glenn Dubin, Trustee. 2. Dr. Elisa Port. 3. Sonia Jones, Dr. Eva Andersson-Dubin, Ramon Parsons, MD, Perri Peltz Ruttenberg. 4. Angela Hunte, Beatrix Miller, Carolina Jones. 5. Dr. Eva Andersson-Dubin, David Reich, MD, Sonia Jones.

4

5

Council of Advocates Breakfast WHEN: November 13, 2013 WHERE: Harlow Restaurant WHO: 1. Kenny Dichter. 2. Corby Kummer (moderator) with Peter May, Chairman of the Boards of Trustees, and President Kenneth L. Davis, MD.

Seventh Annual Greening Our Children Benefit WHEN: May 16 WHERE: Hyatt Regency, Greenwich, Connecticut

1

2

WHO: Ken Cook, Jennifer Beals, Dr. Phillip Landrigan

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Gv

GIVING

The Naming of the Mirken Family Clinical Neuroscience Institute WHEN: April 9 WHERE: The May Faculty Practice Associates, The Mount Sinai Hospital WHO: Richard Zenker, Jane Zenker, Alan Mirken, Joan Mirken, Andrew Zenker, Leslie Rubin, Susan Bressman, MD, Mitchell Rubin, Stuart Sealfon, MD

Children’s Growth Center Dedication WHEN: June 25 WHERE: The Hall Family Center for Pediatric Endocrinology and Diabetes, The Mount Sinai Hospital WHO: Shane Harrison Carley and Karen N. Clarke

Today’s Food Allergy Research/ Tomorrow’s Innovations and Cures WHEN: March 12 WHERE: The Carlyle Hotel, New York City WHO: Trustee Eric Lane and Scott Sicherer, MD, Elliot and Roslyn Jaffe Professor of Pediatrics, Allergy and Immunology and a clinician and researcher in the Jaffe Food Allergy Institute

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1

2

3

4

The 29th Annual Mount Sinai Crystal Party WHEN: May 8 WHERE: Central Park Conservancy Garden, New York City WHO: 1. Stacy Mindich and Eric Mindich, Trustee. 2. Carolyn Sicher and Aaron Woolf. 3. Joan Picket and Joel Picket, Trustee. 4. Lisa Blau and Jeff Blau, Trustee. 5. Steve Hochberg, Senior Vice Chairman of the Boards of Trustees, and Hillary Hochberg. 6. President Kenneth Davis, Steve Hochberg, Peter May. 7. Alice Netter, Trustee and Ken Wyse. 8. Carla Harris, Trustee, and Victor Franklin.

5

6

7

8

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Al

ALUMNI “Old-School” Innovator “We’re basically dinosaurs,” Howard A. Levin, MD,

“We don’t develop widgets to develop widgets.” – Howard A. Levin, MD

CPR by automatically contracting and expanding and a

ISMMS ’86 says, referring to himself and his business

blood-filtration device that helps alleviate symptoms of

partner, Mark Gelfand, co-founders of a successful

congestive heart failure.

medical device incubator called Coridea, Inc.

But Dr. Levin and Mr. Gelfand are perhaps best

Dr. Levin considers himself an “old-school” physi-

known for developing the concept of renal denervation.

ologist. “Mark and I are among the few people left

The pair invented a device, currently in US clinical

who can do systems-level integrated physiology,” he

trials, that can be threaded through a catheter during

says. Though trained as both a

a minimally invasive surgical

biomedical engineer and a heart

procedure to sever the renal

failure transplant cardiologist, Dr.

nerves that transmit information—

Levin has consistently resisted

sometimes erroneously—between

trends in the medical community

the brain and the kidneys. Thus

toward ever more precise

far, renal denervation has proven

specialization, instead preferring

successful in dramatically reducing

to apply his expertise to devising

hypertension in patients whose

technology-based solutions for

disease cannot be successfully

diseases that affect multiple

reduced or controlled by drug

organ systems.

therapies alone—with few

But “dinosaur” is an unlikely

significant side effects.

word to describe Dr. Levin, an

author on 67 issued U.S. patents

destined to be an inventor. In fact,

and a prolific inventor whose innovative medical devices are

HOWARD A. LEVIN, MD

transforming treatment for

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

patients with cardio, pulmonary, and or renal condi-

56

Dr. Levin was not always

after earning his medical degree from Mount Sinai, he was on track for a career in academic medicine.

He spent three years at New York Hospital completing

tions for which drug therapies have failed.

his internal medicine training before beginning a cardi-

Dr. Levin is quick to point out that he and Mr.

ology fellowship at Johns Hopkins School of Medicine.

Gelfand place less emphasis on the technology than

It was at Johns Hopkins that he met Mr. Gelfand and

on identifying a clinical need that they can help meet.

his future as an inventor and entrepreneur began to

Technology is the tool, not the endpoint.

take shape.

“We don’t develop widgets to develop widgets,” says

In 1992, Dr. Levin joined Columbia University Medical

Dr. Levin. “We start with an unmet clinical need, where

Center, where he accepted a position on the faculty

medical and surgical therapies have failed. From

in the Division of Cardiology and became medical

there we look for a known, but unexploited, physi-

director of the ventricular assist program. But in 1996,

ological target and we develop a device to help us take

Dr. Levin left academia to join his first start-up, Cardio

advantage of that target.”

Technologies, Inc., where he served as chief medical

Coridea, Inc. is Dr. Levin and Mr. Gelfand’s umbrella

officer and vice president of research and development.

incubator, which has launched four venture-funded

In 1999, Dr. Levin and Mr. Gelfand teamed up to launch

start-up companies since its inception in 2003. Among

their first start-up, CHF Solutions, where Dr. Levin

their successful inventions: a vest that administers

served as president and chief scientific officer.


“I enjoyed clinical medicine immensely but the

now had an opportunity to learn from Dr. Levin’s

primary reason I left academics was that I felt

experience first-hand: In Fall 2013, he began teaching

limited to a certain extent,” Dr. Levin recalls. “I really

a one-month-long, elective course “Innovation in

wanted the opportunity to look at a number of

Medicine.”

different disease areas and see if I could come up with

“The basic tenets we teach are applicable whether

therapies for them across the board that would help

you’re going into academic medicine or business or

more patients.”

running a private practice,” he says. “Identify the most

The difficulty, he says, comes in designing

important issues, figure out the best way to make

technological interventions that are marketable

what you’re doing successful and attractive, and make

and profitable enough to attract investors who will

sure you achieve your deliverables. The deliverables

finance further research and development. Together,

are different, but the concepts are the same.”

he and Mr. Gelfand evaluate each idea against an

According to Dr. Levin, it’s all about paying forward

array of risks on paper before moving forward.

the unparalleled education he received at Mount

“Most start-ups fail because they’re not good for all

Sinai. “Mount Sinai started me on my career in an

of the different constituents,” Dr. Levin says. In his

amazing way,” he recalls. “I would love to increasingly

case, he says, “A device has to be good for the patient,

be able to give back and help the next generation of

good for the hospital, good for the insurer, good for

physicians achieve their goals.”

the physician.”

Perhaps not surprisingly for an old-school,

Despite these inevitable challenges, he has never

big-picture physiologist, Dr. Levin urges medical

looked back.

students to ground themselves in the fundamentals:

“We discard about 90 percent of ideas we initially

“Take advantage of the outstanding opportunity

come up with based on the paper evaluation,” he

that Mount Sinai gives you to learn about medicine,

estimates. “That’s the problem in developing devices

empathy, compassion. There will always be changes

that actually sell: You’re down in the 5 percent range

in the business of medicine. The one thing you can do

of ideas. For me, I enjoy that. It’s a real challenge.”

is learn to be the best physician you can. All the rest

Students at the Icahn School of Medicine have

will come in time.” – Sara Daniels

DID YOU KNOW?

Founded in 2003, Coridea, Inc. is a medical device incubator that takes a translational health care approach to delivering innovative solutions for cardio, pulmonary, and renal patients who have failed existing drug treatments. Coridea has launched four cardio and renal-focused companies/devices in the past 10 years, and has an impressive IP “hit rate” with 66 total U.S. patents issued, 58 of which have been successfully translated into devices in clinical use or clinical trials.

57


Al

ALUMNI

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Mount Sinai Honors 2014 Jacobi Medallion Recipients Mount Sinai welcomed nearly 500 guests for an evening of celebration for this year’s Jacobi Medallion recipients. The Jacobi Medallion, the highest honor Mount Sinai can bestow, was awarded to seven Mount Sinai doctors; guests also witnessed the passing of the Gold-Headed Cane, a prestigious honor awarded only ten times since 1942. The cane was passed by the previous holder, Harry Spiera, MD, to Jerome Waye, MD, MSH ’63, in recognition of his lifetime of dedication to educating physicians in

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the field of gastroenterology and his stature as one of the world’s leading endoscopists. For more about the distinguished recipients of the 2014 Jacobi Medallion, please visit http://blog.mountsinai.org/blog/2014-jacobi-medallion-honorees PICTURED: 1. Scott L. Friedman, MD, ISMMS ’79, Barbara Murphy, MD, Lynne D. Richardson, MD, Dennis S. Charney, MD, Adrian Greenstein, MD, David L. Reich, MD, MSH ’87, Martin S. Goldstein, MD, MSH ’71, Lester Silver, MD. 2. Guests enjoy the reception at The Plaza Hotel. 3. Jerome D. Waye, MD, MSH ’63. 4. Dr. Lynne D. Richardson with students and staff. 5. Dr. Scott L. Friedman with students and staff. 6. Lyris A. Schonholz, MD, Martin S. Goldstein MD, MSH ’71 and Susan Goldstein.

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

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Raising the Standard at the Icahn School of Medicine at Mount Sinai A new giving society for alumni is in formation and will be growing in the coming months, according to the Office of Alumni and Development. The Society of Alumni Leaders comprise Mount Sinai alumni who are committed to raising the standard of alumni engagement and philanthropy at the Icahn School of Medicine, while supporting scholarships for the School’s students. “Members of the Society serve as ambassadors and advocates for philanthropy,” says David

Muller, MD, Dean for Medical Education and the Marietta and Charles C. Morchand Chair in Medical Education. “Their demonstrated commitment and leadership is set to inspire fellow alumni within the institution and externally.” There are five leadership levels within the Society, and members will receive distinct benefits keyed to the level of their support, including exclusive access to select Mount Sinai events. To learn more about the Society of Alumni Leaders, please contact Mackie Spadaccini at (212) 731-7487 or maclean.spadaccini@mountsinai.org.


RETURN, RECONNECT, REDISCOVER Highlights from Reunion 2014

On Friday, May 9th more than 100 alumni came together at Reunion 2014 to celebrate their time spent at the Icahn School of Medicine and The Mount Sinai

1

Hospital. This year’s reunion paid special tribute to ISMMS graduates from 1974 and 1989, who, along with alumni from many other years, got a glimpse of the future direction of Mount Sinai. The backdrop for this year’s event was the Museum of the City of New York, where guests enjoyed cocktails and a presentation near a newly opened exhibit of photography by artist Aaron Rose, followed

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by dinner on the rotunda balcony overlooking the grand staircase. PICTURED: 1. Members of the Class of 1989: Iris Kopeloff, MD, Berklee Robins, MD, Peter Goldstein, MD, Neil Herbsman, MD, Jamie Fortunoff, MD, Mark Schwartz, MD, Hilary Gleekman-Greenberg, MD, Diana Dorfman Deutsch, MD, Eugene Segall, MD. 2. Lyris A. Schonholz, MD and Theodore Pak, ISMMS MD/PhD Candidate. 3. Benjamin Cohen, MD, ISMMS ’05, Alyson Fox, MD, ISMMS ’04, and Govind Nandakumar, MD, ISSMS ’04. 4. Members of the Class of 1974: Robert Lautin, MD, Guest of Dr. Lautin, Michael Billett, Mark Pruzansky, MD, Henny Billett, MD, Sheila Pruzansky, PhD, Marianne Goodman, MD, Ellen Melvin, MD, Marie Keith, MD. 5. Ira Eliasoph, MD, MSH ’58, and Jose Clemente, PhD. 6. Laure Kahn, MD, ISMMS ’89, MSH ’92, Guest of Dr. Ward, Wendy Ward, MD ISSMS ’89 MSH ’93. 7. Theodore Pak, ISMMS MD/PhD Candidate.

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In Memoriam Mount Sinai Science & Medicine salutes six Trustees who died since the publication of our last issue. We extend our deepest condolences to their family and friends.

Clifford H. Goldsmith, a member

Alan B. Mirken, a Trustee Emeritus

of the Mount Sinai Boards of

of the Mount Sinai Boards of Trustees,

Trustees since 1980, co-founded

established the Alan and Barbara

the Corinne Goldsmith Dickinson

Mirken Department of Neurology at

Center for Multiple Sclerosis in

the Beth Israel Medical Center, where

2000 in memory of his daughter.

he had served as Chair of the Board

He cared very deeply about eradicating multiple

of Overseers. The Mirken Family Clinical Institute at

sclerosis, and was a passionate and generous

Mount Sinai was established due to his longstanding

supporter of such research at Mount Sinai for

support and his efforts to unite the Mount Sinai

many years.

Health System neuroscience programs by encouraging partnership and collaboration throughout the system. Andrew D. Heineman was a longtime supporter of scholar-

Donald Schnabel served for more

ships for the Icahn School of

than 30 years as a Trustee of both

Medicine at Mount Sinai. He

Continuum Health Partners and at

served with distinction as a

St. Luke’s-Roosevelt Hospital. During

Mount Sinai Trustee since 1975,

his tenure, he was an ardent supporter

and was actively involved on the Student Affairs and Mount Sinai Alumni committees. Carol R. Maslow gave many

MOUNT SINAI SCIENCE & MEDICINE / FALL 2014

Alfred R. Stern served on the Mount

years of service on the boards of

Sinai Boards of Trustees since 1963, and

the Beth Israel Medical Center and

was a past Chairman. He was an integral

of Continuum Health Partners.

part of the founding of the Icahn School

She was a past chairman of the

of Medicine as well as the construction

Breast Service Luncheon as well

60

of the Division of Hematology-Oncology and the Medical Ethics Program.

of The Mount Sinai Hospital’s

as a chairman of the Board of Beth Israel’s Robert

Guggenheim Pavilion, both of which greatly expanded

Mapplethorpe Treatment Facility.

Mount Sinai’s teaching, research, and clinical capabilities.

Reunion 2015 will be held Friday, May 8th, 2015 We would love to see you there. If you’d like to be kept up-to-date on the latest information about Reunion 2015, as well as other Sinai events, please send us your current contact information at alumni@mssm.edu.


ARE YOU PART OF

THE CIRCLE?

If you are not, now is the time to join the Mount Sinai Leadership Circle and be part of our exclusive membership events. Members of the Mount Sinai Leadership Circle advance Mount Sinai’s mission: patient care, research, and medical education. Circle members receive invitations to special events during the year—such as a lecture series featuring noted experts discussing the latest medical breakthroughs and other opportunities keyed to your level of giving. For more information on the Mount Sinai Leadership Circle, please contact Al Seminsky at (212) 731-7428 or albert.seminsky@mountsinai.org.

www.philanthropy.mountsinai.org


Non Profit Org. U.S. Postage

PAID Mount Sinai Health System Office of Development One Gustave L. Levy Place, Box 1049 New York, NY 10029-6574

S. Hackensack, NJ Permit No. 897

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