Academic Research Review Council
Richard Kolodner, Ph.D.
Chair, Scientific Review Council
Member, Ludwig Institute for Cancer Research San Diego Branch and Head of the Laboratory of Cancer Genetics
Distinguished Professor of Medicine and of Cellular and Molecular Medicine, UCSD School of Medicine
The major research interest of Dr. Kolodner’s laboratory is using Saccharomyces cerevisiae as a model organism to study the molecular mechanisms by which cells maintain the stability of their genome and prevent the accumulation of mutations and genome rearrangements. The laboratory also works on inherited defects in human recombination and repair genes to understand how such defects cause cancer susceptibility and to understand the basic human genetics of these genes. These studies have involved the routine use of techniques in S. cerevisiae genetics, protein purification, genomics and human genetics.
Tom Curran, Ph.D., FRS
Chair, Basic Cancer Research Peer Review Panel 1
Chief Scientific Officer and Executive Director of the Children’s Mercy Children’s Research Institute
Donald J. Hall Eminent Scholar in Pediatric Research
Professor, Department of Pediatrics,UMKC School of Medicine
Professor, Department of Cancer Biology,University of Kansas School of Medicine
Adjunct Professor of Biomedical Sciences, Kansas City University of Medicine & Biosciences
Dr. Curran discovered the Fos oncogene and its binding partner, p39, which he later showed was the product of the Jun oncogene. His laboratory demonstrated that Fos and Jun function as inducible transcription factors that regulate gene expression in response to extracellular stimuli associated with proliferation, differentiation, cell death and neuronal activation. This work elucidated the signal transduction pathways that go awry in cancer cells and has initiated the use of Fos as a marker for activity-dependent changes in the nervous system.
Peter Jones, Ph.D., D.Sc. (hon)
Chair, Cancer Biology Peer Review Panel
Chief Scientific Officer, Van Andel Research Institute, Grand Rapids, Michigan
A pioneer in the field of epigenetics, Dr. Jones has uncovered basic mechanisms of DNA methylation and its role in cancer. He discovered that 5-azacytidine can induce changes in gene expression and act as a powerful DNA methylation inhibitor, which led to the isolation of the first mammalian determination gene and to the discovery of tumor suppressor genes that are epigenetically silenced in human cancer. The drug 5-azacytadine has been approved for use in treatment of myelodysplastic syndrome.
Richard J. O’Reilly, M.D.
Chair, Translational Cancer Research Peer Review Panel
Chair, Department of Pediatrics and Director of the Bone Marrow
Transplantation Program, Memorial Sloan-Kettering Cancer Center
Dr. Richard J. O'Reilly has been engaged in clinical research and experimental therapeutics focused on allogeneic hematopoietic cell transplantation. He pioneered the development of curative marrow transplantation approaches for the treatment of children with severe combined immune deficiency who lack an HLA matched sibling donor. He introduced the use of matched unrelated donors and T-cell depleted transplants from HLA half matched donors in order to provide a normal blood system without graft vs host disease (GvHD) to patients afflicted with lethal immune deficiencies and leukemia, and subsequently performed the first successful transplants of unrelated marrow for the treatment of leukemia. He and his colleagues developed an approach employing soy bean lectin agglutination and E-rosette depletion for elimination of T lymphocytes from bone marrow allografts. Thereafter, they verified the potential of allogeneic T cell-depleted transplants to prevent GvHD in primate models. Beginning in 1980, they introduced trials of transplants from haplotype matched parents depleted of T-cells by this technique as a treatment for children with severe combined immune deficiency. This experience, which is now one of the world’s largest, clearly demonstrates that such transplants can reconstitute immunity and abrogate GvHD. Indeed, 70% of the patients in the entire series are surviving with immune reconstitution and without GvHD.
Carol Prives, Ph.D.
Chair, Basic Cancer Research Peer Review Panel 2
Professor, Department of Biological Sciences, Columbia University
Dr. Prives’s research has focused on the p53 tumor suppressor since the late 1980’s when she established conditions for purifying and characterizing the p53 protein biochemically and was among the first to show that p53 is a sequence specific transcriptional activator. Her research found that tumor derived mutant forms of p53, especially those that are mutated with high frequency, are defective in such transactivation. Dr. Prives continued to study p53 as a DNA binding transactivator, with special focus on mechanisms by which p53 selects its target genes; and she also provided the first model for stabilization of p53 by genotoxic stress when her group showed that p53 becomes phosphorylated after DNA damage at sites that weaken its interaction with its negative regulator Mdm2. They have continued to study the structure and functional regulation of Mdm2 and its relationship to p53. After the p53 homologues, p63 and p73, were identified, she developed and tested the hypothesis that one of the modes by which some tumor derived mutant forms of p53 elicit pro-oncogenic activities is through down-regulation of the apoptotic functions of p63/p73. Since then, her work has focused on many aspects of the p53 family and on mutant p53. Recently, she has examined mutant p53 pro-oncogenic activities in breast cancer cell lines using the "3D" culture protocol.
Margaret A. Tempero, M.D.
Director, UCSF Pancreas Center
Rombauer Family Distinguished Professorship in Pancreas Cancer Clinical and Translational Science
Professor in Medicine, Division of Hematology/Oncology
Dr. Tempero is Director, UCSF Pancreas Center and Leader of the UCSF Pancreas Cancer Program. She oversees a full portfolio of projects from risk assessment to early detection, biology, and therapeutics in pancreatic neuroendocrine tumors and pancreatic ductal adenocarcinoma. Her personal research career has focused on pancreatic ductal adenocarcinoma, especially in the area of investigational therapeutics. She was a pioneer in the use of antibody-based therapies and helped develop the fixed dose rate concept for gemcitabine. Her group has developed effective gemcitabine combinations and provided a foundation for using CA19-9 as a surrogate for survival in clinical trials, and currently is assessing molecular subtypes and molecular enrichment for selecting new drugs for clinical evaluation. Dr. Tempero directed the first GI SPORE devoted to pancreatic cancer when she was on the faculty of the University of Nebraska and subsequently led the NCI funded U54 Molecular Target Assessment Team at UCSF. She is currently a DreamTeam P.I on a Stand Up To Cancer grant entitled "Targeting Stem Cell Signals in Pancreatic Cancer". Dr. Tempero is a co-investigator on an NIH U01 grant entitled “Chronic Pancreatitis, Diabetes and Pancreatic Cancer: A Prospective Approach”. This is a collaborative project working with investigators at Kaiser to establish cohorts at risk for pancreatic ductal adenocarcinoma. These cohorts will be engaged for prevention and early detection studies.