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Transcript
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