John Hawley

Craig B. Thompson, MD, received the 2003 ASCI Award in recognition of his discovery of the critical role costimulatory receptors play in regulating immune responses. He was the first to demonstrate that CD28 regulates cytokine production, lymphocyte survival, and immune homeostasis. These pioneering studies have contributed to novel treatments for autoimmune disease, transplantation rejection, cancer, and AIDS.

Dr. Thompson is a clinical hematologist/oncologist who started his independent research career by investigating how bone marrow transplant patients mounted antiviral immune responses while on immunosuppressive doses of cyclosporin A. His study of this issue has led to pioneering contributions to basic immunology. His laboratory was the first to uncover the central role of the CD28 costimulatory pathway in the regulation of cytokine production by T cells. The Thompson Laboratory also demonstrated that CD28 contributes to T cell clonal expansion by inhibiting apoptosis, leading to the cloning of the anti-apoptotic genes Bcl-x and XIAP and the development of methods for the in vitro expansion of human CD4 T cells now in use for cancer immunotherapy and HIV treatment. In a landmark series of papers, Dr. Thompson and his colleagues identified the receptor CTLA-4 as a negative regulator of CD28 activation. These pioneering observations led to the current intense clinical investigation of both anti-CD28 Ab and soluble CTLA-4 receptors for the treatment of transplant rejection and autoimmunity.

Dr. Thompson has made a number of other seminal contributions to the understanding of immune cell development, survival, and transformation including: 1) co-discovery of gene conversion as a mechanism of immunoglobulin diversification in avian species, 2) discovery of P nucleotide addition during VDJ recombination, 3) identification of antigen receptor engagement as the mechanism for terminating receptor rearrangement, 4) discovery of the pore forming properties of Bcl-2 proteins and the role of these and related proteins in the regulation of mitochondrial physiology, and 5) discovery of the central but redundant regulatory roles of Bax and Bak in apoptosis.

Dr. Thompson received his undergraduate degree from Dartmouth College and his M.D. degree from the University of Pennsylvania. He received clinical training in Internal Medicine at Peter Bent Brigham Hospital and in Medical Oncology at the Fred Hutchinson Cancer Research Institute at the University of Washington. He is currently the Scientific Director of the Abramson Family Cancer Research Institute and Professor and Chairman of the Department of Cancer Biology at the University of Pennsylvania. In addition to his research contributions, Dr. Thompson has mentored over two dozen students and fellows who have gone on to successful careers in academic medicine.

Ronald A. DePinho, MD, received the 2002 ASCI Award, given on the basis of his fundamental discoveries spanning the fields of cancer research, aging, and chronic degenerative disease. He is a leader in utilizing the experimental power of the mouse to understand the molecular underpinnings of complex human disorders. His contributions have shaped basic understanding of how aspiring cancer cells achieve their lethal endpoint and include the recognition that p53 functions as a tumor suppressor by activating apoptosis in the face of aberrant cell cycling, that INK4a/ARF is a true tumor suppressor, and that ARF is genetically and biochemically linked to the p53 pathway. His studies of p16^INK4a revealed its function as a guardian against environmental carcinogens — an observation with implications in cancer prevention.

He has championed the use of inducible cancer models for the study of host-tumor interactions and the validation of cancer targets. Notably, through this system, he demonstrated the concept of tumor maintenance. His studies of the Myc oncoprotein demonstrated a dominant negative approach in mammalian cells, uncovered a tumor suppressor role for the Myc antagonist Mxi1, and led to the co-discovery of the mammalian Sin3 complex and its link to chromatin regulation. His work on telomerase has shed light on why age is a potent carcinogen, why chronic high-turnover diseases may progress to cancer, and why epithelial cancers emerge with radically altered genomes. He has championed telomere-based crisis as a major mechanism driving chromosomal aberrations characteristic of most human carcinomas. His program also established important pathogenetic links between telomere dysfunction and age-related disorders and chronic degenerative diseases, such as liver cirrhosis.

Dr. DePinho is also dedicated to the development of young physician-scientists and to community initiatives, which have included the organization of numerous courses and meetings focused on mouse genome manipulation and biology.

Dr. DePinho studied Art History and Biology at Fordham University. He received his M.D. degree with distinction in Microbiology and Immunology from the Albert Einstein College of Medicine.

Laurie H. Glimcher, MD, is the recipient of the 2001 ASCI Award in recognition of seminal contributions to our understanding of the transcriptional regulation of lymphocyte subset differentiation.

Christine E. Seidman, MD, is the recipient of the 2000 ASCI Award in recognition of employing molecular genetic approaches in defining the etiology of inherited human disorders and genetic engineering to produce murine models of human disease, with particular emphasis on heart disease.

The 1999 ASCI Award was presented to Dr. Richard Klausner at the Annual Meeting of the American Society for Clinical Investigation in Chicago, Illinois, on April 24, 1999, for the discovery of key mechanisms that regulate metal metabolism and intracellular trafficking.

Dr. Klausner received his undergraduate degree from Yale University and his medical degree from Duke University. After post-graduate medical training at Harvard, he began his research career at the National Cancer Institute in 1979, where he was appointed Director in 1995. Dr. Klausner is well known for his contributions to multiple aspects of cell and molecular biology and cancer research. Over the past five years, he has been recognized as one of the 20 most highly cited scientists in the world in this burgeoning area of biology and biomedical research. Dr. Klausner’s research has illuminated the genetics and biochemistry of metals as essential but toxic nutrients for virtually all forms of life, has illuminated the pathways by which molecules traffic and speak to each other within the cell, and has described novel mechanisms by which genes are regulated. His work has been recognized with numerous honors and awards including the Outstanding Investigator Award from the American Federation of Clinical Research and the William Damashek Prize for Major Discoveries of Hematology. In 1993, Dr. Klausner was elected to the National Academy of Sciences. Dr. Klausner has been the President of the American Society for Clinical Investigation and is the author of over 280 scientific articles and several books. His recent work on the VHL oncogene which plays a major role in human kidney cancer has opened a new approach to studies of growth regulation and cancer.

The first ASCI Award was presented to Stanley J. Korsmeyer, MD, at the annual meeting of the American Society for Clinical Investigation in Washington, D.C., on May 2, 1998, for the identification of key genetic mechanisms that govern cell death and survival.

Dr. Korsmeyer cloned BCL-2 from the t (14;18) chromosomal breakpoint of human follicular lymphoma; his BCL-2 transgenic mice established a new category of oncogenes — regulators of cell death. He identified a large family of proteins, including a partner protein BAX that promotes apoptosis, and characterized their biochemical roles. He further integrated the death pathway by identifying death ligands BAD and BID and their connection with survival factor signaling. His elegant gain and loss of function murine models established the contribution of disordered cell death to immunodeficiency, infertility, degenerative diseases, and cancer. Dr. Korsmeyer’s pioneering observations stimulated an entire field of cell death research and its impact on human disease.

Dr. Korsmeyer, who passed away in March 2005, received numerous awards and recognition for his work.