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GLOBAL IMPACTMount Sinai anesthesiologist Irene Osborn, MD greets

a young patient during a recent service trip to Haiti

T H e M a g a z I n e O f T H e M O u n T S I n a I M e D I c a l c e n T e r

Mount SinaiSCiEnCE & MEDiCinE

IN THIS ISSUE Mount Sinai Around the Globe + Vanquishing Disease + Welcoming an Iconoclast + Helping Hands in Haiti FALL 2011

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Miriam Merad, MD, PhD doesn’t do her father’s — or anyone’s — medicine. Her passion for discovery has the potential to touch millions of lives across the globe.

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“In the lab, we are working to learn more about the tumor-associated immune network and how it could be used synergistically with conventional therapy to cure cancer,” she says. “We focus on the biology of dendritic cells [DC] and macrophages (which are white blood cells present in every tissue). Dendritic cells are a bridge to the outside world, uniquely equipped to sense and inform the immune system when injuries occur and induce immune response to eliminate the injury. DC sense tumor cell proliferation as a tissue injury and can lead to the induction of specific immunity to cancerous cells. It is this unique ability to promote immunity against tumors that could be used as a novel and specific arm against the remaining can-cer cells. Macrophages are cells related to the DC family; their main role is to promote tissue repair and growth and thus in contrast to DC can help tumors grow.”

COLLABORATIVE STUDY

“My lab consists of a mix of basic immunolo-gists, physician scientists, and clinicians. Together we are intent on learning to decipher the processes that regulate DC and mac-rophage ability to modulate tumor growth and progression and come up with novel therapeutic strategies that will synergize with conventional antitumor therapies. Because dendritic cells and macrophages regulate tissue response to all kind of injuries, our work on cancer has implications and potential for a much broader impact on disease: many immune disorders, infectious diseases, autoimmune diseases — including inflamma-tory bowel disease, which is a focus of many investigators at the Mount Sinai Immunology Institute, and brain immune disease.” Over and over, Dr. Merad has success-fully demonstrated the importance of the translational approach and the power of col-laborating across disciplines. Last year, she published a study in Science reporting unan-ticipated and “amazing” findings that resolve a long-standing controversy about the origin of microglia, macrophages of the brain thought to play a key role in the development of many neurodegenerative diseases, such as Alzheimer’s disease, as well as immune diseases, including multiple sclerosis. While much study remains to be done, this result could represent a critical first step toward the eventual discovery of the cause of devastat-ing brain immune and degenerative disease.

By Sima Rabinowitz The little girl rushed to the hospital in the middle of the night was neither ill nor injured. During her childhood in Algeria, Miriam Merad often accompanied her father and mother — a cardiologist and a toxicologist, respectively — to work when they responded, at all hours, to emergencies.

“I came to think of the hospital as my second home,” says Dr. Merad, who grew up to be professor of sciences, medicine, hematology, and medical oncology, and director of the Cancer Immunology Program at Mount Sinai’s Tisch Cancer Institute. “And I was passionate about medicine from a young age. As a heart doctor, my father was always on call, and my mother was developing the first center of toxicology in Algeria. There was endless talk in our house about sci-ence and medicine.” She recalls with great appreciation her parents’ work and commitment to their profession and to improving health in what was then, and remains, a country with enormous unmet medical needs. At the same time, she insists, “We can’t do our fathers’ medicine. They did everything by the book. That is probably what was appropriate in that time and place. But now, we need to constantly innovate. We must do ‘crazy things.’ And we have the capacity to do that here at Mount Sinai.”

DRIVEN TO CUREDoing “crazy things,” Dr. Merad explains, means embracing the unexpected and acting on novel ideas and new ways of approaching complex problems. By “we,” she is referring to physician scientists in academic medicine who are not constrained by the limitations and preoccupa-tions of the pharmaceutical industry, where drug

discovery often happened in the past. “We are driven by one principal concern,” she adds,

“To cure disease.” “Driven” captures Dr. Merad’s nature and career perfectly. Trained as a physician (she received her medical degree in oncology from the University of Algiers and then specialized in hematapoetic cell-blood stem cell-trans-plantation at a hospital in France) and as a scientist (she received her PhD in immunology through a joint program at Stanford University and the University of Paris VII), she is dynamic and enthusiastic, enormously productive, and intensely dedicated to understanding some of the most complex questions of human biology. Great innovation and creativity will continue to arise, she is convinced, from the collabora-tion of researchers and physicians from diverse disciplines who bring distinct knowledge, expertise, and perspectives to their common work. Clinicians must identify patients’ unmet medical needs, help researchers understand what diseases and disorders require attention, and share information about how existing treat-ments affect their patients, and basic scientists must help decipher the biological mechanisms underlying disease. The process of understand-ing and treating disease depends, much like the body itself, on intricate networks and support systems. Together, scientists and doctors must strive to translate breakthroughs in the labora-tory to effective therapies with the potential to prevent, diagnose, treat, and cure disease.

SUPPORT SYSTEMS

The complex support systems and networks that both sustain healthy cells and contribute to their injury and subsequently to disease is precisely the focus of Dr. Merad’s work. For a long time scientists believed, she explains, that cancer resulted solely from cell prolifera-tion (uncontrolled growth). We now know that all cells need “to be fed.” They require the right niche to grow, an environment provided by stromal cells that consist of numerous cell types, including immune cells, which exist in high number in tumor lesions. Indeed, patients who die from their cancer always die of tumor relapse: No matter how efficient conventional therapies — such as chemotherapy and radia-tion therapy — can be at eliminating big tumor masses, they always fail to eliminate all of the tumor cells. Studying the support systems that help remaining tumor cells to grow and develop can lead to the cure of tumors, explains Dr. Merad.

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THE BIG PICTURE — AND THE SMALLWith focus on — and success in — identifying some of the key causes of illness and disease, Dr. Merad’s research can have a critical impact, influencing the understanding of multiple diseases and conditions affecting countless patients around the world. Nonetheless, she is committed to the plight of patients with rare diseases, as well. She is currently engaged in identifying the cause of a rare disease called Langerhans cell histiocytosis, characterized by the accumulation of abnormal dendritic cells in tissues. This disease affects mainly children. Dr. Merad serves on the board of a consor-tium organized by the parents of a child who suffers from this disease. Once a year the consortium organizes a workshop where basic scientists, clinicians, and patients meet. A child afflicted with Langerhans histiocytosis speaks to the group and clinicians introduce patients with difficult or refractory cases. “Basic scien-tists are always very touched and inspired by

the patient session,” Dr. Merad notes, “because no matter how basic or clinically oriented scien-tists are, we all strive to have an impact on human disease.” It is this concept of deep and continuous interactions among basic scientists, physician scientists, and clinicians that Dr. Merad enjoys and wants to expand further at Mount Sinai. She initiated a cancer immunotherapy focus group where basic immunologists and oncologists meet monthly to discuss how promising data on animal models can be translated into cancer patients. She also serves as an assistant director of the MD/PhD program and continuously preaches the importance of translational research. Dr. Merad and Ross L. Cagan, PhD, Mount Sinai’s vice dean of graduate studies, are collaborating to start a new graduate course for first-year PhD students called “Translational Science”; the goal of the course is to expose students to the clinical world and teach them principles of translating basic research into medicine.

At a time of great uncertainty in the world in so many regards, when obtaining funding for even the most worthwhile projects can be a challenge, Dr. Merad is optimistic about the prospects for success and achievement in academic medicine in general and at Mount Sinai in particular. Her colleagues clearly agree. It’s hard to find an investigator or an MD/PhD student at Mount Sinai who, in the course of talking about translational research, does not mention the importance and influ-ence of Dr. Merad’s work. “It’s a wonderful time to be in academic medicine, a pioneering time,” she affirms. Mount Sinai’s Institutes model is a productive and effective one, she says, and the medical center’s history, support, and appreciation for the “crazy” and creative work of collabora-tion, and the innovation that ensues, have the potential for the great and lasting impact that is every scientist’s, physician’s — and patient’s — dream.

“Dendritic cells are a bridge to the outside world, uniquely equipped to sense and inform the immune system when injuries occur.” – Miriam Merad

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