Various functions within the Immune System The laboratory is currently involved in research investigations that deal with tumor cell induction of apoptosis in cytotoxic anti-tumor effector cells, and on the mechanism of resistance of tumor cells to immunotherapy. In the first project, we have demonstrated that interaction of tumor target cells with natural killer (NK) cells resulted in the induction of apoptosis in the sensitive target cells and thereafter the induction of apoptosis in the cytotoxic effector cells. This project investigates the underlying biochemical and molecular mechanisms by which the tumor target cells trigger programmed cell death in the cytotoxic cells. The role of MHC-killer inhibitory receptors (KIR) and killer activating receptors (KAR) as well as the role of the FC-receptor in intracellular signaling pathways that result in NK apoptosis are being investigated. The second project examines the resistance of tumor cells to cytotoxicity and apoptosis by cytotoxic lymphocytes. The mechanism of resistance to Fas-ligand, TRAIL and TNF-a (effector pathways in cytotoxic lymphocytes) are being examined. In addition, we have demonstrated that resistant tumor cells can be sensitized by various agents to killing by these cytotoxic effector mechanisms. The underlying mechanisms of immunosensitization are being examined. Aside form the in vitro studies, translational in vivo studies to enhance gene/immunotherapy strategies against resistant tumor cells are also being evaluated.

tumor cell induction of apoptosis in cytotoxic anti-tumor effector cells,

Dr. Karin was born in Tel Aviv, Israel and received the Bachelor of Science degree in 1975 from Tel Aviv University, with a major in Biology. In 1975 he arrived in the US and in 1979 received a Ph.D. degree in Molecular Biology from the University of California, Los Angeles. Dr. Karin followed his graduate studies with postdoctoral fellowships at the Fox Chase Institute for Cancer Research, working in the laboratory of Dr. Beatrice Mintz, and the laboratory of Dr. John Baxter at the University of California, San Francisco. Dr. Karin joined the faculty at the University of California, San Diego in 1986, where currently he is a Distinguished Professor of Pharmacology.

Protein Kinases, Oncogenes, Transcription Factors, Signal Transduction, Gene Expression

Dr. Mane completed his PhD at the age of 28 years from The University of Bombay and postdoctoral studies from The Johns Hopkins University School of Medicine. He is the director of Yale Center for Genome Analysis, one of the most scientifically productive and accomplished Genome Centers. He has published more than 100 papers in reputed journals and has served as an ad hock reviewer of several journals. He is also one of the principle investigators of a $12 million grant from NIH/NHGRI to establish the Yale Center for Genome Analysis.

Cell Differentiation; Cell Lineage; Hematologic Diseases; Hematopoiesis; Neoplasms

Dr. Amy Hong Zhang, M.D., Ph. D., is currently an Assistant Professor in the Department of Pathology in University of Texas-M.D. Anderson Cancer Center in Houston, TX, specializing on breast cancer pathology. Prior to joining UT-MDACC, Dr. Zhang was an Assistant Professor in the Department of Pathology in the Baylor College of Medicine from 2006 to 2009. Dr. Zhang is an American Board certified practicing pathologist since 2003. Dr. Zhang has expertise in diagnosing breast cancer and the interpretation of the biomarkers relevant to breast cancer for patient care. Dr. Zhang is also actively participating in clinical teaching for the residents/fellows on surgical pathology. As an independent laboratory researcher, Dr. Zhang supervises research scientists and trainees on translational and laboratory research working on the characterization and development of new molecules significant for breast tumorigenesis. Her academic activities in recent years have led to a series of first author, co-author and senior author publications in recognized peer-reviewed journals.

As a practicing pathologist and an Assistant Professor in the Department of Pathology at M. D. Anderson with a focus on breast cancer, I have expertise in diagnosing breast cancer and the interpretation of the biomarkers relevant to breast cancer. In addition, my Ph.D. training background provided me with broader experience and interest. As an independent laboratory researcher, I work with trainees in my laboratory on the characterization and development of new molecules significant for breast tumorigenesis.

Jose Costa, M.D., is Professor of Pathology and Medicine at Yale University School of Medicine. A graduate of Barcelona Medical School, Dr. Costa trained in Anatomical Pathology at Colorado University (G.B. Pierce) and Washington University (P. Lacy; L.V. Ackerman). He went on to do research as a Fogarty International Fellow (1973) in the laboratory of A.S. Rabson at NCI, were he stayed to eventually become the Anatomical Pathology Branch Chief at the Clinical Center, NIH Bethesda, MD. Elected to a Chair in Pathology at the University of Lausanne (1982), he directed between 1983 and 1993 the Institut Universitaire de Patologie, developing a program of advanced diagnostics and collaborating both with the ISREC and the Lausanne Branch of the Ludwig Institute.

Bone Neoplasms; Medical Oncology; Musculoskeletal Diseases; Orthopedics; Pathology; Molecular Diagnostic Techniques; Translational Medical Research

Dr. Mane completed his PhD at the age of 28 years from The University of Bombay and postdoctoral studies from The Johns Hopkins University School of Medicine. He is the director of Yale Center for Genome Analysis, one of the most scientifically productive and accomplished Genome Centers. He has published more than 100 papers in reputed journals and has served as an ad hock reviewer of several journals. He is also one of the principle investigators of a $12 million grant from NIH/NHGRI to establish the Yale Center for Genome Analysis.

Cell Differentiation; Cell Lineage; Hematologic Diseases; Hematopoiesis; Neoplasms

Jose Costa, M.D., is Professor of Pathology and Medicine at Yale University School of Medicine. A graduate of Barcelona Medical School, Dr. Costa trained in Anatomical Pathology at Colorado University (G.B. Pierce) and Washington University (P. Lacy; L.V. Ackerman). He went on to do research as a Fogarty International Fellow (1973) in the laboratory of A.S. Rabson at NCI, were he stayed to eventually become the Anatomical Pathology Branch Chief at the Clinical Center, NIH Bethesda, MD. Elected to a Chair in Pathology at the University of Lausanne (1982), he directed between 1983 and 1993 the Institut Universitaire de Patologie, developing a program of advanced diagnostics and collaborating both with the ISREC and the Lausanne Branch of the Ludwig Institute.

Bone Neoplasms; Medical Oncology; Musculoskeletal Diseases; Orthopedics; Pathology; Molecular Diagnostic Techniques; Translational Medical Research

Dr. Karin was born in Tel Aviv, Israel and received the Bachelor of Science degree in 1975 from Tel Aviv University, with a major in Biology. In 1975 he arrived in the US and in 1979 received a Ph.D. degree in Molecular Biology from the University of California, Los Angeles. Dr. Karin followed his graduate studies with postdoctoral fellowships at the Fox Chase Institute for Cancer Research, working in the laboratory of Dr. Beatrice Mintz, and the laboratory of Dr. John Baxter at the University of California, San Francisco. Dr. Karin joined the faculty at the University of California, San Diego in 1986, where currently he is a Distinguished Professor of Pharmacology.

Protein Kinases, Oncogenes, Transcription Factors, Signal Transduction, Gene Expression

Various functions within the Immune System The laboratory is currently involved in research investigations that deal with tumor cell induction of apoptosis in cytotoxic anti-tumor effector cells, and on the mechanism of resistance of tumor cells to immunotherapy. In the first project, we have demonstrated that interaction of tumor target cells with natural killer (NK) cells resulted in the induction of apoptosis in the sensitive target cells and thereafter the induction of apoptosis in the cytotoxic effector cells. This project investigates the underlying biochemical and molecular mechanisms by which the tumor target cells trigger programmed cell death in the cytotoxic cells. The role of MHC-killer inhibitory receptors (KIR) and killer activating receptors (KAR) as well as the role of the FC-receptor in intracellular signaling pathways that result in NK apoptosis are being investigated. The second project examines the resistance of tumor cells to cytotoxicity and apoptosis by cytotoxic lymphocytes. The mechanism of resistance to Fas-ligand, TRAIL and TNF-a (effector pathways in cytotoxic lymphocytes) are being examined. In addition, we have demonstrated that resistant tumor cells can be sensitized by various agents to killing by these cytotoxic effector mechanisms. The underlying mechanisms of immunosensitization are being examined. Aside form the in vitro studies, translational in vivo studies to enhance gene/immunotherapy strategies against resistant tumor cells are also being evaluated.

Tumor cell induction of apoptosis in cytotoxic anti-tumor effector cells.

Dr. Amy Hong Zhang, M.D., Ph. D., is currently an Assistant Professor in the Department of Pathology in University of Texas-M.D. Anderson Cancer Center in Houston, TX, specializing on breast cancer pathology. Prior to joining UT-MDACC, Dr. Zhang was an Assistant Professor in the Department of Pathology in the Baylor College of Medicine from 2006 to 2009. Dr. Zhang is an American Board certified practicing pathologist since 2003. Dr. Zhang has expertise in diagnosing breast cancer and the interpretation of the biomarkers relevant to breast cancer for patient care. Dr. Zhang is also actively participating in clinical teaching for the residents/fellows on surgical pathology. As an independent laboratory researcher, Dr. Zhang supervises research scientists and trainees on translational and laboratory research working on the characterization and development of new molecules significant for breast tumorigenesis. Her academic activities in recent years have led to a series of first author, co-author and senior author publications in recognized peer-reviewed journals.

As a practicing pathologist and an Assistant Professor in the Department of Pathology at M. D. Anderson with a focus on breast cancer, I have expertise in diagnosing breast cancer and the interpretation of the biomarkers relevant to breast cancer. In addition, my Ph.D. training background provided me with broader experience and interest. As an independent laboratory researcher, I work with trainees in my laboratory on the characterization and development of new molecules significant for breast tumorigenesis.