不良研究所

POSITIONS AND EMPLOYMENT
1979-1980 MRC Postdoctoral Fellow, Weizmann Institute of Science, Rehovot, Israel
1980-1982 MRC Postdoctoral Fellow, Dept. of Anatomy, 不良研究所
1983-1991 Assistant Professor, Dept. of Surgery, 不良研究所
1984-1989 Medical Research Council of Canada Scholar
1990-1993 Chercheur Boursier, Fonds de la Recherche en Sant茅 du Qu茅bec.
1992-2000 Associate Professor, Dept. of surgery and Oncology, 不良研究所
1993-1994 Visiting Professor, Dana Farber Cancer Institute, Harvard Medical School, Boston, Mass
1997-2000 Associate Professor, Dept. of Medicine, 不良研究所
2001- Professor - Departments of Surgery, Medicine & Oncology, 不良研究所
2004-2005 Visiting Scientist - National Institute of Health, Bethesda MD
2005 Visiting Scientist鈥� Technion Institute of Technology - Haifa, Israel
2005 Joels Hebrew University Visiting Professor (on sabbatical leave)
2011- Senior Scientist 鈥� Research Institute of the 不良研究所 Health Center
2013 Visiting Scholar - University of California San Diego, Department of Pharmacology
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Personal Statement
The focus of my research program has been the biology of cancer metastasis. In this context, our work has centered on the role of the microenvironment (ME) in liver metastasis (LM) of GI cancers. Our overarching goal has been translational and our aim has been to identify targets and develop therapeutic interventions to block the spread of malignant disease to, and within the liver. In the course of these studies, our research team was among the first to show that cancer cells entering the liver induce a rapid inflammatory response resulting in a cytokine cascade that enables trans-endothelial migration and liver colonization. We also discovered that in this TNF-飦� rich ME, the metastatic cells can escape death through autocrine IL-6/STAT3 signaling. We identified The TNF receptor 2 (TNFR2) as a survival factor for regulatory T cells and myeloid-derived suppressor cells in the immune-tolerant ME (IME) of colon cancer LM. This work led to the identification of a sexual dimorphism in the control of the liver IME and the discovery of the important role that estrogen plays in this regulation. Our lab was also among the first to document the importance of the IGF-axis to cancer cell invasion and metastasis in general, and LM, in particular. Several strategies for targeting the IGF-axis were developed, leading to the bioengineering of the IGF-Trap - a potent inhibitor of growth and metastasis of several aggressive cancers including pancreatic ductal adenocarcinoma (PDAC). More recently, we discovered that the IGF-Trap affects the innate immune response to metastatic cells in the liver, blocking the polarization of infiltrating neutrophils and macrophages to an immunosuppressive phenotype and profoundly changing the immune landscape associate with LM. We subsequently optimized a combinatorial immunotherapy for the prevention and treatment of PDAC LM consisting of the IGF-Trap and anti PD-1 antibodies. In addition, our work on the biology of PDAC was recently extended to targeting a protein that drives PDAC progression (IMP-1) and our current work focuses on gaining mechanistic insight into its role in PDAC growth and metastasis.