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Douglas Bishop, Ph.D. Dr. Bishop's group focuses on the mechanisms cell use to repair broken DNA molecules. DNA breaks occur during normal cell growth, during meiosis, the special cell divisions that gives rise to gametes, and when cells are exposed to radiation. DNA repair is relevant to cancer in two ways. First, when normal cells fail to repair DNA, mutations occur and these mutations can lead to cancer. Second, many effective cancer treatments, such as radiation treatment, and some forms of chemotherapy, work because they kill tumor cells by damaging tumor cell DNA. In this case, DNA repair contributes to treatment failure by protecting tumor cells from the effects of therapeutic agents. Dr. Bishop's lab uses genetic techniques to study the proteins that carry out a form of DNA repair called "recombinational repair" in yeast and vertebrate cells. The lab has recently identified a group of proteins that work as "assembly factors" to build the protein complexes needed to repair DNA. One of the proteins that appears to play the role of assembly factor is BRCA1p which is encoded by the BRCA1 gene. The BRCA1 gene helps prevent cancer, people who inherit defective copies of this gene have a high risk of breast cancer and other malignancies. In addition to studying recombination genes and proteins in more detail, Dr. Bishop's group is working in collaboration with Dr. Weischelbaum's group to identify inhibitors of recombination complex assembly. Their experiments have already provided evidence that assembly inhibitors will increase the effectiveness of certain types of chemotherapy. In addition to studying the repair process itself, Dr. Bishop's group studies proteins that help cells recover from DNA damage by stopping cell growth when damage is present. The arrest caused by these proteins allows time for the DNA repair process to occur. Recent work from the Bishop lab indicates that the same proteins that halt cell growth after DNA damage also appear to be important for generating or maintaining normal chromosome structure. Curriculum V. S. Education 1976-80 B.A. 1981-88 Ph.D., Cellular and Developmental Biology Post-Graduate Training Research Assistant Post-doctoral Fellow and Research Associate Academic Appointments Assistant Professor University of Chicago Associate Professor University of Chicago Professor University of Chicago Amherst College Harvard University Cold Spring Harbor Laboratory (1980-81) Harvard University (1988-92) 1993-1999 1999-2008 2008-present Committee Appointments Committee on Genetics Graduate Student Recruitment and Admission Committee (1994-95) Chair, Committee on Genetics, Student Affairs Committee (1995-present) Wade Committee on Ph.D. Program Reorganization (1996) Committee on Cancer Biology, Student Admissions Committee (1997) Committee on Cancer Biology, Curriculum Committee (1997-present) Biological Sciences Division Facilities Planning Committee (1998-present) Professional Experience 1980-81 Cold Spring Harbor Laboratory Research Assistant, Laboratory of Dr. David Kurtz 1988-91 Harvard University, Post-doctoral Fellow, Prof. Nancy Kleckner, Advisor 1991-1992 Harvard University, Research Associate 1993-99 University of Chicago, Assistant Prof. Department of Radiation and Cellular Oncology Department of Molecular Genetics and Cell Biology Committee on Genetics, Committee on Cancer Biology 1999-2007 University of Chicago, Assoc. Prof. (with tenure) Department of Radiation and Cellular Oncology Department of Molecular Genetics and Cell Biology Committee on Genetics, Committee on Cancer Biology 2008 -present University of Chicago, Professor (with tenure) Department of Radiation and Cellular Oncology Department of Molecular Genetics and Cell Biology Committee on Genetics, Committee on Cancer Biology Teaching 1993-present Lecturer for Basic Research Summer Course for Radiation and Cellular Oncology Residents, Summer Quarter; 3-6 students. (3 lecture hours) 1995-2004 Lecturer in Graduate Course on Genetic Mechanisms (MGCB315) 2007-present Winter Quarter; 6-15 students. Course Director 2003-2004. (22.5 lecture hours) 1998-1999 Lecturer in Advanced Undergraduate/Graduate Course on Fundamentals in Molecular Biology (BIOS289, MGCB310); 25-30 students. (12 lecture hours) 2000-present Lecturer in Graduate Course on Genetic Analysis (MGCB314) Fall 30-40 students (12-15 lecture hours). Course director 20002-present . 2006, 2008 Lecturer in Undergraduate Course on Genetics (BIOS 20192) Winter Quarter; 75 students (15 lecture hours). 2006-present Lecturer and Course Director Undergraduate course on the Genetics of Model Organisms, (BIOS21236) Autumn Quarter, 15 students (12 lecture Hours). Laboratory Research Mentoring 1994-present University of Chicago, Ph.D students Past Stephen Gasior, Ph.D. (2001) Instructor, U. New Orleans Jeremy Grushcow, Ph.D. (2002) Attorney, Shearman and Sterling, LLPChicago Eurie Hong, Ph.D. (2003) Head Curator, Stanford Genome Database Brian Orelli, Ph. D. (2004) Biotech Stock Analyst, The Motley Fool , Inc. Teresa Holzen, Ph.D. (2005) Post-doc, U of Colorado, Denver Present Melissa McMahill, 6 th year CG Sean Sheridan, 6 th year CG Parisha Shah, 5 th year MGCB Richard Martin, 5 th year MGCB Susan Ferrari , 4 th year CB 1992-present University of Chicago Undergraduates (*=honors project) Past June Oshiro, Ph.D*: Ph.D. in Microbial Genetics, Rutgers University, Medical Editor, Mayo Clinic Chris Calderone: Ph.D. candidate, Program in Biophysics. Harvard University. Caroline Sham*: MD-Ph.D. candidate UCLA Stephanie Xie*: Ph.D. candidate in Biology. MIT Jason Chon, MD: Chief Resident, Department of Diagnostic Radiology, Rush Hospital, Ken Park, MD: Nephrology fellow, UCSD. Present Daniel Zwick ‘09 Post Doctoral Mentoring Past Yuri Nikolski, Ph. D. CEO GeneGO, Inc. Anamitra Bhattacharrya, Ph. D. Staff Scientist, Integrated Genomics Miki Shinohara, Ph. D. Assistant Professor, Osaka University Emir Khatipov, Ph. D. National Center for Biotechnology Information Ozlem Yildez, Ph. D. post-doc U. of Chicago (Dr. Kenan Onel) Present Dong Lin , Ph.D. Peking U. University of Chicago, M.D. and M.D. candidate mentoring ( 1993-94,99-01, 03) : Past Arno Mundt, M.D. , Assoc. Prof. Radiation Oncology. U. of California, San Diego Phil Connell, M.D., Assist Prof, U. of Chicago. Audrey Kuang, M.D. (2001). Resident Santa Clara Valley Medical Center Ph.D. Advisory Committee Member (1994 -present ): Past ChristianFritze, John Choy, Scott Diede, Peter Andolfatto, Lisa Henninger, Dina Newman, Jon Soderholm, Stephanie Mewborn, Adam Conway, Oliver Hohman,, Sarah Hall, Troy McSherry, Keira VonBesser, Nicole Hagemann, Hilary Knobloch, Simmone Longerich, Aparna Palakodeti, Jenny Brace, Yanwen Jiang. Present Elizabeth Montegna , Sunita Shukla, Sho Yano, Melissa Mefford, David Tussini, Cara Rabik, Jay Shrestha, Karen Ouyang, Adi Alon, Chinonye Nnakwe Research Projects Ongoing: National Institutes of General Medical Sciences P.I. Douglas K. Bishop 4/1/93-3/28/11 ( uninterrupted funding for 18 years) 2 RO1 GM50936 $454,854/yr 50% effort Meiotic Interactions of the RecA Homolog Dmc1 The long-term goal of this project is to determine the molecular mechanism of meiotic recombination. National Cancer Institute P.I. Douglas. K. Bishop 4/1/03-4/1/08 1 RO1 CA095777 $289,556/yr 20% effort Genetic Dissection of BRCA1 Function. To identify functional domains of the multifunctional breast cancer susceptibility gene BRCA1. Research Projects Completed: U.S. Army Medical Research and Materiel Command P.I. Ralph Weichselbaum (PI) . 12/10/01 – 1/9/05 DAMD17-02-1-0035 $489,253 CO-P.I . Douglas K., Bishop 5% effort Title: Targeted Inhibition of DNA Repair in Prostate Cancer Therapy Illinois Department of Public Health (Post-doctoral fellowship) Douglas K. Bishop, on behalf of Ozlem Yildiz $35,000 7/1/04-6/30/05 Title: Structure-function Analysis of the Breast Cancer Susceptibility Protein BRCA1 U.S. Army Medical Research and Materiel Command P.I. Douglas K. Bishop 9/15/00-10/14/03 DAMO17-00-1-0196 Amount $339,075 5% effort Title: Inhibitors of XRCC3 To isolate peptide inhibitors of the recombinational repair protein Xrcc3p using phage display methods and test the ability of these inhibitors to enhance the effectiveness of the chemotherapeutic cis-platinum treatment in breast cancer. Mary Kay Ash Charitable Foundation P.I. Douglas K. Bishop 7/1/00-6/30/02 $100,000 5% Effort Title: Targeted Enhancers of Chemotherapy in Ovarian Cancer To test the ability of peptide inhibitors of human Xrcc3 protein to enhance the sensitivity of ovarian tumor cells to the killing effects of cisplatin. CaPCURE P.I. Douglas K. Bishop 2/1/00-1/31/02 Title: Enhancement of Cisplatin by inhibition of the DNA Repair Protein XRCC3 $100,000 10% Effort To test the ability of peptide inhibitors of human Xrcc3 protein to enhance the sensitivity of prostate tumor cells to the killing effects of cisplatin. NSF Division of Biological Infrastructure P.I. : Stephen Kent 9/1/02-10/31/05 Co-P.I.: Douglas Bishop DBI-0216251 Award Amount: $250,000 Title: Functional Proteomics - Acquisition of a Biacore 3000 system for Surface Plasmon Resonance measurements" Intramural Service 1994-95 Committee on Genetics Graduate Student Recruitment and Admission Committee 1995-1999 Chair, Student Affairs Committee for Committee on Genetics 1996 Member, Wade Committee on Ph.D. Program Reorganization 1997 Committee on Cancer Biology, Student Admissions Committee 1997-2002 Committee on Cancer Biology, Curriculum Committee 1998-1999 Biological Sciences Division Facilities Planning Committee 2000 Co-chairman, Department of Radiology Review Committee 2001-2007 Committee on Research Resources (Core facility oversight) 2001-2006 Committee for Faculty Re-appointments and Promotions 2001-2003 Department of Molecular Genetics and Cell Biology, Faculty Recruitment Committee 2001-2002 Ludwig Professor Recruitment Committee. 2002-2003 Department of Human Genetics, Chair Recruitment Committee. 2002-present Chairman, Committee on Genetics (Ph. D. program with about 25 candidates) 2002-2007 Divisional Executive Committee 2002-2005 University Council of the Faculty Senate Extramural Service 1993-1996 Leukemia Research Foundation, Scientific Advisory Board, grant review 1994-1997, 2003 National Science Foundation, ad hoc grant review 1995-1996 United States Department of Agriculture, ad hoc grant review 1998, 2002,2005 National Institute of General Medical Sciences, ad hoc study section member Genetics, Biochemistry, MBC2, MGA, MGC Study sections. 2005 National Cancer Institute Intramural Review Group (Laboratory of Biochemistry) 2006-present National Institute of General Medical Sciences MGC Study section, permanent member 1998-present Associate Editor: Genes to Cells 2003-4 American Society for Microbiology, Chairman Division X (Eukaryotic Microbiology). 2002 Gordon Research Conferences, co-Vice Chair for Conference on Meiosis 2004 Gordon Research Conferences, co-Chair for Conference on Meiosis 1993-present Peer reviewer for the following journals:Cancer Research, Cell, Chromasoma, The EMBO Journal, Gene, Genes and Development, Genetics, Journal of Cell Biology, Molecular and Cell Biology, Nature, Nature Structural and Molecular Biology, The Plant Cell, Proc. Natl. Acad. Sci., USA, Science, Oncogene, J. Biol. Chem., PLOS Biology, PLOS Genetics, Cancer Research, Genes to Cells, Journal of Molecular Bioloy, Journal of Cell Biology Invited Lectures Only two types of presentations are listed: External 50-minute invited seminars at academic institutions and 1540 minute invited platform presentations at international meetings (•) . 1993 •Genetics Society of America, Yeast Meeting, Seattle, WA “Cytological detection of RecA homologues in meiosis” 1994 University of Western Ontario, Department of Biology, London Ontario, CANADA “Cytological detection of meiotic recombination” •Gordon Conference on Meiosis, Plymouth State College, Plymouth, NH “Detection of RecA homologues Rad51 and Dmc1 by immunostaining” University of Wisconsin, Department of Genetics, Madison, WI “Cytological detection of recombination complexes.” Loyola Medical School, Department of Molecular Biology, Maywood, IL “Recombination complexes and checkpoint control in meiosis.” 1995 Osaka University, Department of Biology, Toyonaka, JAPAN “Meiotic recombination and reductional chromosome segregation” •FEBS Lecture Course: Genetics, Biochemistry and Ultrastructure of Meiosis Obertraun, AUSTRIA “Meiotic recombination complexes and regulation of meiotic division” University of Indiana, Department of Biology, Bloomington, IN “Meiotic recombination complexes and regulation of meiotic division” 1996 •Gordon Conference on Meiosis, Colby-Sawyer College, New London, New Hampshire “Regulation of recombination partner choice” •EMBO Workshop: Mechanisms and Consequences of Genetic Recombination, Seillac, FRANCE “Activation of a DMC1-independent pathway for resolution of Meiotic DSBs” •FASEB Summer Research Conference on Yeast Chromosomes, Snowmass, CO “Regulation of meiotic recombination” 1997 Yale University Medical School, Department of Genetics, New Haven, CT “Regulation of meiotic recombination” University of Arizona, Department of Biology, Tucson, AZ “Regulation of meiotic recombination” •DNA Replication, Recombination, and Repair Symposium, Nagoya, JAPAN “Cytological investigation of meiotic recombination” 1998 •Genetics Society of America Symposium on DNA Repair: Bacteria to Humans, Airlie House, Warrenton, VA “Assembly of recombination complexes and checkpoint control during meiosis. •Gordon Conference on Meiosis, Colby-Sawyer College, New London, NH “Assembly of recombination complexes” •FASEB Summer Research Conference on Yeast Chromosomes, Snowmass, CO “Assembly of recombination complexes” • University of Texas, Center for Molecular Medicine, San Antonio, TX “Assembly of meiotic recombination complexes” • Wayne State, Center for Molecular Medicine and Genetics, Detroit, MI “Assembly of meiotic recombination complexes” 1999 University of Oregon, Department of Molecular Biology “Assembly and regulation of meiotic recombination complexes” Cornell University, Department of Genetics, Ithaca, NY “Assembly of recombination complexes” •FASEB Summer Research Conference on Recombination and Genome rearrangement, Snowmass, CO (Session Chair) “Assembly of recombination complexes” 2000 Brown University, Providence, RI “Assembly of homologous recombination complexes •Gordon Conference on Meiosis, Colby-Sawyer College, New London, NH “Assembly of recombination complexes” •EMBO Workshop: Mechanisms and Consequences of Genetic Recombination, Seillac, FRANCE(Session Chair) “Yeast Dmc1 promotes strand annealing and D-loop formation in vitro” • National Academy of Science Colloquium “Links between recombination and replication: Vital roles of recombination” Irvine, CA. “Assembly of RecA-like recombinases: Distinct roles for mediator proteins in mitosis and meiosis 2001 •Society for Experimental Biology Annual Meeting. Canterbury, UNITED KINGDOM “Structural Features of recombination complexes in S. cerevisiae” •Radiation Research Society Annual Meeting. San Juan, Puerto Rico “Regulation of Assembly of Recombinational Repair Complexes” University of Wisconsin, Department of Genetics, Madison, WI “Coordination of Meiotic Recombination” Sloan-Kettering Cancer Institute, New York, NY “Coordination of Meiotic Recombination” 2002 •Keystone Symposium on Molecular Mechanisms of DNA Replication and Recombination, Snowbird, CO “The Role of Dmc1 and Tid1 in Homologous Strand Invasion and Crossover Interference” •EMBO Workshop: Mechanisms and Consequences of Genetic Recombination, Seillac, FRANCE “Coordination of DNA Ends during Meiotic Recombination” • Gordon Conference on Meiosis (vice Chairman), Colby-Sawyer College, New London, NH “Coordination of DNA Ends during Meiotic Recombination” •FASEB Summer Research Conference on Yeast Chromosomes, Snowmass, CO (Session Chair) “Role of DNA Damage Checkpoint Genes in Regulating Meiotic Recombination” •Federation of Asian Organizations for Biochemistry and Molecular Biology, Annual Meeting. TAIWAN “Role of Dmc1 and Tid1 in Strand Invasion and Crossover Control” •Banbury Conference on Recombination (Discussion Leader). Cold Spring Harbor, NY. “Meiotic Recombination” 2003 •Gordon Conference on Radiation Oncology, Ventura, CA “Peptide inhibition of XRCC3” •FASEB Summer Research Conference on Recombination and Genome rearrangement, Snowmass, CO “Genetic Analysis BRCA1 function in DT40 Cells” •EMBO Workshop: Meiosis, Obertraun, AUSTRIA “Specialized functions of Rad51 and Dmc1” 2004 •EMBO Workshop: Mechanisms and Consequences of Genetic Recombination, Seillac, FRANCE “Tid1 promotes dissociation of Dmc1 from non-specific sites on chromatin” •Gordon Conference on Meiosis, Colby-Sawyer College, New London, NH (Meeting Co-Chairman) “Introductory Overview” 2005 Institute of Biological Chemistry, Academica Sinica Nankang, TAIWAN “ Regulation of Recombinase Assembly during DNA repair and meiosis” Hsin Chu Univeristy Hsin Chu, TAIWAN “ Regulation of Recombinase Assembly during DNA repair and meiosis” •FASEB Summer Research Conference on Recombination and Genome rearrangement, Snowmass, CO “Suppression of BRCA1 mutants by overexpression of RAD51” University of Iowa, Department of Genetics, Iowa City, Iowa” “ Regulation of Recombinase Assembly during DNA repair and meiosis” •American Society for Microbiology Annual Meeting, Atlanta GA (Session Chair) “Tid1 promotes dissociation of Dmc1 from non-specific sites on chromatin” •EMBO Workshop: Meiosis, El Escorial, SPAIN (Session Chair) “Tid1 promotes dissociation of Dmc1 from non-specific sites on chromatin” Department of Radiation Oncology Washington U. Med. School, St. Louis, MO. “Recombinase Dynamics in Breast Cancer and Meiosis” 2006 U. of California, Davis, CA “Dynamics of Meiotic Recombinase” •Gordon Conference on Meiosis, Colby-Sawyer College, New London, NH “Evidence for Synthesis-Dependent Strand Annealing” 2007 U. of Indiana, Bloomington Indiana. “Recombinase Dynamics in Cancer and Meiosis