JAMES ALLISON, Ph.D.

Specialty: Cancer

Institution: Chairman, Immunology Program; Director, Ludwig Center of Cancer Immunotherapy; David H. Koch Chair in Immunologic Studies; Attending Immunologist, Department of Medicine; Investigator, Howard Hughes Medical Institute, Memorial Sloan- Kettering Cancer Center

Other Titles: Executive Committee, Geoffrey Beene Cancer Research Center, Memorial Sloan-Kettering Cancer Center

Notes : The general area of our research is the molecular immunology of the T cell antigen receptor complex, co-stimulatory receptors, and other molecules involved in T cell activation. We are particularly interested in defining those signaling events that lead to differentiation of naive T cells and those that determine whether antigen receptor engagement will lead to functional activation or inactivation of T cells. The lessons learned in these basic studies are used to develop new strategies for the treatment of autoimmune diseases and for immunotherapy of cancer.

T lymphocytes play a major role in the immune response, performing both direct effector and indirect regulatory roles. T cells develop in the thymus, where gene segments recombine to generate diverse antigen receptors (TCR), and selective processes occur that give rise to a functional repertoire capable of recognizing foreign antigens in the context of self major histocompatibility antigens. We are examining the molecules and processes involved in the differentiation and activation of T cells in the mouse.

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Website: Sloan-Kettering - Immunology: James Allison

JOHANNA JOYCE, Ph.D.

Specialty: Cancer

Institution: Junior Faculty Chair, Geoffrey Beene Cancer Research Center, Memorial Sloan-Kettering Cancer Center

Other Titles: Associate Member int he Cancer Biology Program at MSKCC

Notes :Johanna Joyce is an Associate Member in the Cancer Biology Program at Memorial Sloan Kettering Cancer Center, New York, & an Associate Professor in Cornell University Graduate School of Medical Sciences.  She received her Ph.D. in Biology from the University of Cambridge, England in 1999, & did her postdoctoral training at UCSF.  Dr. Joyce has received career development awards from the Sidney Kimmel Foundation, the Rita Allen Foundation and the V Foundation for Cancer Research, and was named to a Geoffrey Beene Junior Faculty Chair at MSKCC in 2007.  Her group’s research interests are to understand the mechanisms by which stromal cells in the tumor microenvironment regulate cancer development, metastasis, & response to therapy, with a particular focus on the roles of innate immune cells & proteases.

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ROSS L. LEVINE, M.D.

Specialty: Cancer

Institution: Junior Faculty Chair, Geoffrey Beene Cancer Research Center, Memorial Sloan-Kettering Cancer Center

Other Titles: Assistant Member, Human Oncology and Pathogenesis Program

Notes :I am a physician-scientist with a specific interest in the genetics and therapy of myeloid malignancies, including the myeloproliferative neoplasms polycythemia vera, essential thrombocytosis, and primary myelofibrosis.

The focus of the Levine lab is to improve our understanding of the genetic basis for activation of signal transduction pathways in myeloid malignancies, and to use this knowledge to improve therapies for patients with these disorders. In particular, current research is focused on elucidating the role of oncogenic disease alleles in the pathogenesis of BCR-ABL negative myeloproliferative disorders (MPD), specifically polcythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (MF), and on developing molecularly targeted therapies for these disorders. While in the laboratory of Gary Gilliland at Harvard Medical School, Dr. Levine, along with three other groups, identified JAK2 mutations in patients with polycythemia vera, essential thrombocytosis, and myelofibrosis. We subsequently identified gain of function mutations in the thrombopoietin receptor (MPLW515L/K) in patients with JAK2V617F negative ET and PMF, and in collaboration with Linda Scott and Tony Green identified mutations in exon 12 of JAK2 in JAK2V617F-negative PV. Our current efforts are focused on the following areas:

• Identification of somatic mutations which activate signal transduction in JAK2V617Fnegative MPD, using candidate gene, genome-wide, and functional approaches.
• Investigation of the role of different signaling pathways in hematopoietic transformation by activating mutations in JAK2 and MPL.
• Characterization of inhibitors of JAK2 kinase activity with a potential role in the treatment of PV, ET, and PMF using in vitro and in vivo assays, and elucidation of the mechanisms of resistance to JAK2 inhibitors using in vitro systems.
• Development of novel genetic screens to identify additional oncogenic alleles in hematopoietic malignancies with pathogenetic and therapeutic significance.

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JOAN MASSAGUÉ, Ph.D.

Specialty: Cancer

Institution: Chair, Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center

Other Titles: Executive Committee, Geoffrey Beene Cancer Research Center, Memorial Sloan-Kettering Cancer Center

Notes :We are interested in how growth factors, signaling pathways, and gene expression programs control normal cell proliferation and cancer cell metastasis. The development and maintenance of multicellular organisms requires tight control over the proliferation, differentiation, movement, organization and death of their constituent cells. Intricate molecular communication networks have evolved to control these processes. Our work is focusing on how cells receive, read and relay such signals, and how disruptions in these processes lead to tumor formation and cancer metastasis. We are approaching these questions through the rich venue provided by the transforming growth factor- (TGFb) pathway, as well as through the direct identification of metastasis genes and functions.

With nearly forty related members in the human genome, TGFb represents one of the most prominent and functionally versatile families of cytokines. This family -the TGFbs, nodals, activins, bone morphogenetic proteins (BMPs), myostatins, and anti-Muellerian hormoneexert profound effects on every aspect of cell behavior. Produced by many cell types or restricted to just a few, different TGFb family members guide early stages of embryo development and tissue homeostasis throughout life. We uncovered key steps in this signaling pathway by identifying the TGFb and BMP receptors and elucidating their mechanism of activation . These receptors are serine/threonine kinases and their substrates are the Smad transcription factors. We showed that Smad C-terminal phosphorylation by TGFb and BMP receptor kinases, and Smad linker phosphorylation by MAPK, GSK3 and other protein kinases, are key events in Smad regulation. We are identifying Smad interactions with transcription cofactors and ubiquitin ligases that are supported by these phosphorylation events. These findings are paving the way for new discoveries on the function and network integration of the TGFb and BMP pathways.

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LARRY NORTON, M.D.

Specialty: Cancer

Institution: Deputy Physician-in-Chief, Breast Cancer Programs; Medical Director, Evelyn H. Lauder Breast Center; Norna S. Sarofim Chair in Clinical Oncology, Memorial Sloan-Kettering Cancer Center

Other Titles: Executive Committee, Geoffrey Beene Cancer Research Center, Memorial Sloan-Kettering Cancer Center

Notes : I am a board-certified medical oncologist with broad interests in cancer prevention, diagnosis, and treatment. In my clinical practice I care for women with breast cancer, and I am now Deputy Physician-in-Chief for Breast Cancer Programs at Memorial Sloan-Kettering and Medical Director of the Evelyn H. Lauder Breast Center.

My research concerns the basic biology of cancer; the mathematics of tumor causation and growth; and the development of approaches to better diagnosis, prevention, and drug treatment of the disease. I am involved in many areas of research including identifying the genes that predispose people to cancer or that cause cancer, developing new drugs, monoclonal antibodies that target growth factor receptors, and vaccines. A major milestone in my research career was the development of an approach to therapy called "dose density," or "sequential dose density." This is a new and more effective way of using anticancer drugs, based on a mathematical model I developed with my colleagues, which maximizes the killing of cancer cells while minimizing toxicity.

I am currently the principal investigator of a program project grant from the National Cancer Institute (NCI) that is aimed at better understanding breast cancer in the laboratory and in bringing these advances into clinical practice.

On a national level, I was formerly the Chair of the Breast Committee of the NCI's Cancer and Leukemia Group B. I was President of the American Society of Clinical Oncology (ASCO) from 2001 to 2002, and was appointed by President Clinton to serve on the National Cancer Advisory Board (the board of directors of the NCI).

Among many awards over the course of my career, I was honored to receive ASCO’s highest honor, the David A. Karnofsky Award, and was McGuire Lecturer at the San Antonio Breast Cancer Symposium. I am an author of more than 350 articles and many book chapters, have served as a visiting professor throughout the United States, Canada, South America, Europe, Israel, and Asia, and also have trained many cancer doctors and researchers.

CHARLES L. SAWYERS, M.D.

Specialty: Cancer

Institution: Chair, Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center

Other Titles: Dr. Sawyers is past President of the American Society of Clinical Investigation, serves on the National Cancer Institute's Board of Scientific Councilors, and is a Member of the Institute of Medicine, National Academy of Sciences. He has received numerous honors and awards, including the Richard & Hinda Rosenthal Foundation Award (American Association of Cancer Research), the David A. Karnofsky Award (American Society of Clinical Oncology), the Dorothy P. Landon-AACR Prize for Translational Cancer Research, and in 2009, the Lasker~DeBakey Clinical Medical Research Award.

Notes : Dr. Sawyers is investigating the signaling pathways that drive the growth of cancer cells, with an eye toward designing new treatment options for patients with chronic myeloid leukemia, prostate cancer, and glioblastoma. Our laboratory is focused on characterizing signal transduction pathway abnormalities in various cancers with an eye toward translational implications. One example is chronic myeloid leukemia (CML) which is caused by the BCR-ABL fusion gene, expressed as a consequence of the Philadelphia chromosome translocation. In collaboration with Brian Druker at Oregon Health Sciences University, we developed the ABL kinase inhibitor imatinib/Gleevec as primary therapy for patients with CML. Shortly thereafter, my group discovered that resistance to imatinib is caused by BCR-ABL kinase domain mutations. We worked closely with John Kuriyan's group to examine the structural consequences of these mutations on the ABL kinase domain and postulated that second generation ABL kinase inhibitors that bind to ABL differently from imatinib might retain activity against imatinib-resistant mutants. In collaboration with scientists at Bristol Myers Squibb, we showed that the dual Src/Abl inhibitor dasatinib has such properties in preclinical models, then co-led the clinical development of dasatinib as treatment for imatinib-resistant CML. Subsequently, we found that dasatinib resistance occurs through additional, novel BCR-ABL mutations, some of which remain sensitive to imatinib, making a strong case for combined ABL kinase inhibitor treatment to prevent the emergence of resistant subclones.

A second project in my group is explores the molecular basis of prostate cancer and mechanisms of resistance to hormone therapy. This work is currently focused on the role of the androgen receptor in disease progression, even when tumors progress to the hormonerefractory stage. After demonstrating that higher levels of androgen receptor are necessary and sufficient to confer resistance to current antiandrogens, we collaborated with UCLA chemist Michael Jung to discover a small molecule inhibitor that targets the increased levels of androgen receptor found in hormone refractory disease by a novel mechanism. A phase I-II trial of this compound (MDV3100), now underway at MSKCC and other sites, has shown impressive clinical responses in men with castrate-resistant prostate cancer, including those who have progressed on chemotherapy. MDV3100 will undergo phase III clinical testing beginning in 2009. Current projects are deciphering mechanisms of resistance to MDV3100, dissecting AR function using RNA interference screens and examining crosstalk between AR and other common molecular lesions in human prostate cancer such as PTEN loss and TMPRSS2-ERG gene fusions.

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DAVID SCHEINBERG, M.D., Ph.D.

Specialty: Cancer

Institution: Chair, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center

Other Titles: Executive Committee, Geoffrey Beene Cancer Research Center, Memorial Sloan-Kettering Cancer Center

Notes : The overall goals of this laboratory are to develop novel targeted immunotherapies based on effectors of the immune system and to understand their mechanisms of action as well as the mechanisms of resistance to them. This includes passive agents (antibodies, targeted nano-devices, and ligands) and active agents (vaccines). An important goal is to take these new therapies into human clinical trials for testing. We have developed alpha particle therapies, targeted beta emitters, oncogene product peptide vaccines, and are presently developing prototype targeted nano-machines. Recently, our lab developed a molecular nanogenerator that releases alpha particles inside cancer cells. This is now being tested in humans.

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CRAIG B. THOMPSON, M.D.

Specialty: Cancer

Institution: President and Chief Executive Officer, Memorial Sloan-Kettering Cancer Center

Notes : Dr. Thompson, 57, a renowned cancer researcher and clinician, has served since 2006 as Director of the Abramson Cancer Center at the University of Pennsylvania and Associate Vice President for Cancer Services of the University of Pennsylvania Health System.

As director of the Abramson Cancer Center, Dr. Thompson oversaw the work of several hundred cancer researchers as well as more than 300 full-time physicians and faculty across the University of Pennsylvania Health System involved in cancer prevention, diagnosis, and treatment. During his tenure, his accomplishments included the opening of a new multidisciplinary cancer outpatient facility; the development of the first proton therapy center in the Mid-Atlantic region; and the expansion of Abramson’s translational research effort.

Dr. Thompson’s current research focuses on the role that metabolic changes play in the origin and progression of cancer. He has also done pioneering research on the genes that control programmed cell death and how the misregulation of such genes can contribute to cancer. In earlier work he contributed to the development of innovative treatments for autoimmune diseases and leukemia.

In 1999, Craig Thompson joined the University of Pennsylvania as the founding scientific director of the Abramson Family Cancer Research Institute (the basic science arm of the Abramson Cancer Center), the University’s first chair of the Department of Cancer Biology, and a professor of medicine.

Dr. Thompson attended Dartmouth College and completed his studies at Dartmouth Medical School. He received his MD degree from the University of Pennsylvania in 1977 and completed his residency at Harvard’s Peter Bent Brigham Hospital in 1979. Following his residency, he spent two years as a senior resident at Boston University while serving as a medical officer in the US Navy assigned to the Naval Blood Research Laboratory. He spent a total of eight years as a Navy medical officer, including two years at the Naval Blood Research Institute, three years at the National Naval Center/Naval Medical Research Institute, and three years as a clinical research associate at the Fred Hutchinson Cancer Institute, in Seattle, Washington.

In 1987, Dr. Thompson joined the University of Michigan’s Department of Medicine. And in 1993, he was recruited by University of Chicago as the first director of the Gwen Knapp Center for Lupus and Immunology Research and professor in the departments of medicine and molecular genetics and cell biology.

In addition, from 1989 through 1993, Dr. Thompson was a Howard Hughes Medical Institute (HHMI) associate investigator, and an HHMI investigator from 1993 to 1999.

Dr. Thompson is a board-certified internist and medical oncologist, and has extensive research experience in cancer, immunology, and translational medicine. In 2003, he was elected to the Institute of Medicine and in 2005 was elected to the National Academy of Sciences. He currently serves as chair of the HHMI Medical Advisory Board. He is also a member of the Board of Directors of the Association of American Cancer Institutes and the American Association for Cancer Research, and is a member of the Lasker Prize Jury. Dr. Thompson has been a member of the advisory boards of several cancer centers including St. Jude Children’s Research Hospital and the University of Texas MD Anderson Cancer Center.

ANDREA VENTURA, M.D., Ph.D.

Specialty: Cancer

Institution: Junior Faculty Chair, Geoffrey Beene Cancer Research Center, Memorial Sloan-Kettering Cancer Center

Other Titles: Assistant Member, Cancer Biology & Genetics Program

Notes : Our lab studies cancer-associated microRNAs (miRNAs).MiRNAs constitute a family of small non-coding RNAs that modulate the expression of protein coding genes in a sequence-specific manner. They are found in all bilateria and account for a significant fraction of vertebrate genes. The human genome, for example, contains over five hundred miRNAs. Despite the intense scrutiny they have recently received, the exact biological function of most miRNAs is still largely unknown.

A small, but relevant, number of human miRNAs have been recently shown to participate in the pathogenesis of human cancers, acting as oncogenes or as tumor suppressor genes, or affecting the metastatic process. The goals of our lab are to investigate the biology of this subclass of miRNAs, understand their normal functions in development and tumorigenesis, and determine whether they can be used as effective novel anticancer targets.

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