Phil Hanawalt's CV

Philip C. Hanawalt

Curriculum Vitae


Last updated: October 2014

I. Education

Deep Springs College, CA 1949-1950 Liberal Arts
Oberlin College, OH1950-1954 Physics major B.A. 1954
Yale University, CT1954-1955 Physics M.S. 1955
Yale University, CT1955-1958 BiophysicsPh.D. 1959
Univ. of Copenhagen, Denmark1958-1960 Bacterial PhysiologyPostdoctoral
Caltech, Pasadena, CA1960-1961 Molecular Biology & GeneticsPostdoctoral

II. Appointments - Stanford University, California

Research Biophysicist and Lecturer, Biophysics Laboratory and Graduate Program 1961-65
Associate Professor of Biology, Department of Biological Sciences 1965-70
Director, Biophysics Graduate Program 1968-85
Director of Graduate Studies in Biology 1969-72; 1990-93
Professor of Biology1970-
Program Director, Cell and Molecular Biology Training Program1973-84
Member, Medical Scientist Training Program Committee, School of Medicine1975-80
Member, Advisory Committee on Engineering in Biology and Medicine1976-79
Member, Task Force on Biohazards1977-79
Chair, Administrative Panel on Radiological Hazards1978-80
Member, Committee on Cancer Biology1978-81
Member, Committee on Research1981-84
Professor of Dermatology (Joint appointment), School of Medicine1979-
Chair, Department of Biological Sciences1982-89
Chair, Second Senate ad hoc Committee on the Professorate1988-90
Member, Program in Molecular and Genetic Medicine1989-
Member, 23rd Senate of the Academic Council1990-92
Member, Advisory Committee for Medical Free Electron Laser Center1991-93
Member, School Planning Group, School of Humanities and Sciences1991-93
Member, Graduate Training Program in Biotechnology1994-
Howard H. and Jessie T. Watkins University Professor1997-2002
Member, Stanford Comprehensive Cancer Center2006-
The Dr. Morris Herzstein Professorship in Biology2008-

III. Government Service and Advisory Committees (Partial List)

Physiological Chemistry Study Section, National Institutes of Health (NIH) 1966-70
Advisory Committee on Nucleic Acids and Protein Synthesis, American Cancer Society1972-76
Chair, US National Committee, Intl Union of Pure and Applied Biophysics (IUPAB) 1969-75
Member, IUPAB Commission on Education and Development1975-80
Advisory Committee, Environmental Health Sciences Center, Univ. California, Berkeley1976-83
Chair, cluster group on "Molecular Effects: Interactions with Chemicals and Viruses" for Federal Strategy for Research into Biological Effects of Ionizing Radiation1979-80
Advisory Committee on Low Dose Radiation Program for Natl Cancer Institute, USPHS 1980
Workshop on Mechanisms of Toxicity and Carcinogenicity for
Congressional Task Force on Environmental Cancer and Heart and Lung Disease
1981
Chemical Pathology Study Section, National Institutes of Health1981-84
Scientific Advisory Board, Univ. Texas Cancer Ctr, Science Park, Smithville (Chair 1988-90)1984-90
Predoctoral Fellowship Review Panel, National Science Foundation1985
Board of Scientific Counselors, Division of Biometry and Risk Assessment, NIEHS1987-90
Visiting Committee, Brookhaven Natl Laboratory, Dept of Biology (Chair, 1992) 1987-92
Chair, Advisory Committee, Center for Environmental Health Sciences, MIT 1988-92
Outside Review Committee, NASA Center for Research and Training in Radiation Health Lawrence Berkeley Laboratory--Colorado State University Consortium1991-96
Advisory Committee on Biosciences and Biotechnology, Los Alamos Natl Laboratory, NM1993-95
Special Review Committee, National Cancer Institute1993
Scientific Advisory Board, Xenometrix, Inc., Boulder, Colorado1993-97
Chair, External Advisory Board, Environmental Health Sciences Ctr, Sealy Ctr for
Molecular Science, University of Texas Medical Branch, Galveston
1994-97
Outside Review Committee, Lawrence Berkeley Laboratory, University of California1994
Scientific Advisory Board, Office of Environmental Health Hazard Assessment, CA-EPA1994-98
External Advisory Committee, City of Hope Clinical Cancer Research Center1995-
Toxicology Advisory Committee, The Burroughs-Wellcome Fund (Chair 1997-2000)   1995-
Scientific Advisory Board, Fogarty International Center, NIH 1995-99
Board on Radiation Effects Research, NAS/NRC Commission on Life Sciences1995-98
Consultant, Wireless Technology Research, Ontario, Canada1996
External Review Working Group, Natl Institute of Environmental Health Sciences, NIH 1996-98
MRC Molecular/Cellular Medicine Board, Review of Cell Mutation Unit, Brighton, UKH1996
Outside Evaluation Committee, Medical Genetics Center, Southwest Netherlands1996
Committee on Health Risks of Exposure to Low Levels of Ionizing Radiation,
BEIR Phase I, NRC Commission on Life Sciences
1997-98
Council for Extramural Grants, American Cancer Society 1998-07
Board of Trustees, Oberlin College1998-2007
Chair, External Advisory Board, Program on Structural Biology of DNA Repair (SBDR),
Lawrence Berkeley Lab
2001-
External Visiting Committee, Department of Biological Sciences, Univ. Southern CA2001
NICHD external site visit committee2001, 2006
External review committee, Director of NIEHS2001
Genetics Study Section Boundaries Team, Center for Scientific Review, NIH2002
Abbott-ASM Lifetime Achievement Award Selection Committee,
American Acad. of Microbiology
2003-2006
External Advisory Com. UT MD Anderson Cancer Ctr, TX, Prog. on Processing Complex Lesions 2004-2007
Consultant, Achaogen Inc, South San Francisco, CA 2005
International Advisory Board, Chulabhorn Research Institute, Bangkok, Thailand 2005-2008
Special Conferences Committee, American Association for Cancer Research 2005-
Working Group, Integral Translational Research on DNA Repair (NIEHS)2006
NCI intramural site visit committee member, NIH2009
External Examiner, Biotech Prog. Universiti Tonku Abdul Rahman, Kuala Lumpur, Malasia2010-13
External Reviewer for Cancer Research, UK (Quinquennial Review)2010

IV. Editorial Service

Board of Reviewing Editors:Science1995-01
Managing Editor/Founding EditorDNA Repair: Mutation Research1982-93
Senior Editor:Cancer Research2003-09
Editorial Board:Proceedings of the National Academy of Sciences U.S.A.current
 
Editorial Board: Mechanisms of Ageing and Developmentcurrent
 
Editorial Board: Agingcurrent
 
Editorial Board: Cancer Research, 1984-97; Gene Expression 1990-94; Environ. Molec. Mutagen. 1994-97
Editorial Board: Biotechniques (-2006); DNA Repair; Genes and Environment (Japanese EMS)current
Associate Editor:Environmental Health Perspectivescurrent
Associate Editor:Molecular Carcinogenesiscurrent
Honorary Editorial Board: Libertas Academica; Translational OncoGenomics2006-

V. Professional Recognition and Awards (from 1981)

Fellow, American Association for the Advancement of Science 1981
Inaugural Award Lecture, Lord Dowding Fund for Humane Research, London1982
Spanish Academy of Science & Catalan Society for Biology Lectureship, Barcelona1982
Annual "Frontiers in Biology" Lectureship, Case-Western Reserve University, Cleveland1986
Outstanding Investigator Research Grant, National Cancer Institute, NIH 1987-1994;
1994-2001
Member, National Academy of Sciences, USA1989
Distinguished Lecturer of NIEHS, 6th Annual H. L. Falk Memorial Lecture1990
Excellence in Teaching Award, Northern California Chapter, Phi Beta Kappa1991
Annual Award for Outstanding Research, Environmental Mutagen Society1992
Peter and Helen Bing Award for Distinguished Teaching, Stanford University 1992
Fellow, American Academy of Microbiology1993
Fogarty Senior International Fellowship, at the Imperial Cancer Research Fund Labs, U.K1993
President, Environmental Mutagen Society1994
Annual Research Award, American Society for Photobiology1996
Second Severo Ochoa Memorial Honors Lecture, New York University1996
Chair, Gordon Conference on Mutagenesis1996
Honorary Doctor of Science, Oberlin College, Ohio1997
International Mutation Research Award for Excellence in Scientific Achievement 1997
IBM-Princess Takamatsu Lectureship, Tokyo, Sendai and Kumamoto, Japan 1999
Partab Varandani Memorial Lecture, Wright State University 1999
Chair, Gordon Conference on Mammalian DNA Repair 1999
Inaugural John Abelson Family Lecture, Washington State University2000
Ellison Medical Foundation Senior Scholar Award2001-2005
Student Mentoring Award,Environmental Mutagen Society2001
Foreign Associate, European Molecular Biology Organization (EMBO)2001
Honorary Member, German DNA Repair Network2002
John B. Little Award in Radiation Sciences, Harvard School of Public Health2002
Sonneborn Lecture, Indiana University2002
Rothschild-Yvette Mayent-Institut Curie Award, Paris2003
Keynote Lecture, ASM Intl Conference on DNA Repair and Mutagenesis, Southampton, Bermuda2004
President/Organizer 9th International Conference on Environmental Mutagens, San Francisco2005
Special Issue of Mutation Research Vol. 577(1,2) "Mechanisms of DNA Repair" dedicated to P. Hanawalt2005
Doctor Honoris Causa, University of Bio Bio, Concepción, Chile2006
Centennial Lecture, AACR 99th Annual Meeting, Los Angeles2007
Honorary Trustee, Oberlin College, Ohio2007
Visiting research scholar, Frontier Biosciences Graduate School, Osaka University, Japan2007
Second Lawrence Grossman Lecture, Johns Hopkins University, Bloomberg School of Public Health2008
Elected Fellow of the American Academy of Arts and Sciences (AAAS)2008
Doctor Honoris Causa, University of Seville, Spain2008
Appointed to the Dr. Morris Herzstein Professorship in Biology at Stanford University2008
Elected member of the American Academy of Arts and Sciences2008
Keynote lecture, 10th International Conference on Environmental Mutagens, Florence, Italy2009
Elected Vicechair/Chair Gordon Conference on DNA damage,mutation and cancer for 2012/20142010
Three publicaions selected for Journal of Biological Chemistry Centennial "Classics"2010
AACR-Princess Takamatsu Memorial Lectureship Award2011
Keynote lecture, 3rd Erling Seeberg symposium on DNA Repair, NOrway2012
Doctor Honoris Causa, University of Buenos Aires, Argentina2012
Plenary Lecture, 11th Int. Conf. on Environmental Mutagens, Foz do Iguassu, Brazil2013
Chair, Gordon Research Conference on “DNA Damage, Mutation and Cancer”, Ventura, CA2014
Allan V. Cox Medal for Faculty Excellence Fostering Undergraduate Research at Stanford University2014
Appointed to Fulbright Specialist Roster, Council for International Exchange of Scholars (CIES)2014
Keynote Lecture in Opening Session, 16th Int. Congress on Photobiology, Cordoba, Argentina 2014
Doctor Honoris Causa, National University of El Litoral, Santa Fe, Argentina2014

VI. Professional Societies

American Association for Cancer Research (AACR):
- Program Committee: Chair, Biochemistry Section 1990
- Special Conferences Committee 1991-94; 2005-08
- Board of Directors1994-97
- Chair, Ad Hoc Committee on Research Integrity and Ethics1994
American Society for Biochemistry and Molecular Biology
Fellow, American Society for Microbiology
American Chemical Society
American Society for Photobiology, Charter Member
Biophysical Society, Charter Member
- Executive Board 1969-71
- Program Chair1971
- Nominee for president1971
Environmental Mutagenesis and Genomics Society (EMGS)
- Chair, Future Directions Committee 1990-92
- Program Chair/President Elect 1993
- President 1994
- Council Member 2000-03
- Executive Board 2001-03
- Chair, Alexander Hollaender Outreach Committee 2011-14
European Molecular Biology Organization (EMBO), Foreign Associate 2001 -
Genetics Society of America
National Academy of Sciences USA 1989 -
Radiation Research Society
Sigma Xi
American Academy of Arts and Sciences 2008

VII. Scientific Conferences Organized

*Note that most of these meetings have been held at ski resorts in the winter
Annual Meeting, Biophysical Society, New Orleans, Louisiana (Program Chair)1971
Molecular Mechanisms for DNA Repair, Squaw Valley, California (Organizer & Program Chair)1974
DNA Replication and its Regulation, Squaw Valley, California - (Co-Chair with M. Goulian)1975
DNA Repair Mechanisms, Keystone, Colorado - (Co-chair with E. C. Friedberg)1978
Chemical Carcinogenesis and Oncogenes, Chemical Pathology Study Section Workshop,
Steamboat Springs, Colorado (Co-organizer)
1984
Introduction and Expression of Genes in Eukaryotes, Biology Affiliates Symposium,
Stanford Univ
1985
Mechanisms and Consequences of DNA Damage Processing, Taos, New Mexico
- (Co-chair with E. C. Friedberg) (Keystone Symposium)
1988
Genomic Instability and Cancer, Tamarron, Colorado
- (Co-chair with C. Harris and J. Rowley) (Keystone Symposium)
1991
Cellular Responses to Environmental DNA Damage, Banff, Alberta, Canada
- (Co-chair with M. Paterson) (AACR Special Conference in Honor of Richard Setlow)
1991
Annual Meeting, Environmental Mutagen Society, Norfolk, Virginia (Program Chair) 1993
Risk Assessment in Environmental Carcinogenesis, Whistler Resort, British Columbia
- (Co-chair with J. Swenberg) (AACR/EMS Special Conference)
1994
Gordon Conference on Mutagenesis, Plymouth, New Hampshire (Vice Chair 1994) Chair1996
Gordon Conference on Mammalian DNA Repair, Ventura, California (Vice Chair 1997) Chair1999
DNA Repair in the central nervous system, Winter Conferences on Brain Research,
Breckenridge, Colorado, Panel Chair
2000
President/Organizer, 9th Intl Conference on Environmental Mutagens, San Francisco 2005
Gordon Conference on DNA damage, mutation and cancer, Vicechair 2012, Chair 2014

VIII. Teaching

Twenty-nine graduate students have completed their Ph.D. in Hanawalt's laboratory; over 60 postdoctoral research
associates, fellows and visiting senior scientists have participated in Hanawalt's research program at Stanford since
1962. The laboratory has maintained an international flavor with participants from 35 different countries over the years.

Courses taught at Stanford University: (Current courses underlined)

VIX. Principal Research Accomplishments

As a graduate student, Hanawalt initiated studies in the laboratory of R. B. Setlow at Yale University to provide quantitative assessment of the inhibitory effects of ultraviolet light (UV) on DNA synthesis in E. coli and to suggest that "recovery mechanisms can eventually restore the DNA synthesis. . . ." That work led a few years later to his co-discovery of DNA excision-repair. During postdoctoral study (with O. Maalèe in Copenhagen) he discovered that protein synthesis is required to initiate the bacterial DNA replication cycle. That work was essential to the formulation of the "replicon" concept in the early 1960s and it led to a standard procedure for synchronizing DNA replication cycles.

Hanawalt has been a productive researcher in the field of DNA repair since his pioneering discovery of repair replication in E. coli in 1963. He also first demonstrated repair replication in mycoplasmata and in a eukaryote (Tetrahymena) and he has developed a number of important experimental approaches for studying repair, beginning with the BrdUrd density labeling method for resolving semiconservatively replicated DNA from parental DNA containing repair patches. Hanawalt's approach was used by James Cleaver in 1968 to document a DNA repair defect in xeroderma pigmentosum (the first example of a human disease with DNA repair defect). The method was also used to validate the widely-used phenomenon of unscheduled DNA synthesis as a measure of DNA repair. Other significant research contributions from Hanawalt's laboratory have included: the demonstration of preferential mutagenesis by N-methyl nitrosoguanidine at DNA replication forks and its application to mapping genes; early evidence for membrane association of DNA replication complexes in E. coli and in mammalian cells; discovery of long-patch excision-repair in E. coli and the demonstration that it is an inducible component of the RecA-LexA regulatory circuit; discovery of a gene controlling nucleoside uptake in E. coli; development of permeabilized bacterial and mammalian cell systems to study excision-repair pathways; demonstration of enhanced survival of UV irradiated Simian Virus 40 upon treating the host cells with low doses of UV or chemical carcinogens; discovery that the repair enzyme, T4 endonuclease V, operates processively on damaged DNA; discovery that certain types of damage in transfecting plasmid DNA markedly enhances the efficiency of stable transformation in human cells; and the discovery that UV irradiation of short sequences of nucleotides can result in their ligation through pyrimidine dimerization, providing a plausible mechanism for prebiotic assembly of high molecular weight duplex DNA.

In 1982 Hanawalt and his colleagues reported the first example of intragenomic DNA repair heterogeneity: chemical adducts in centromeric alpha DNA sequences in African green monkey kidney cells were not as efficiently repaired as in the genome overall. In 1983 Mansbridge and Hanawalt discovered that cells from xeroderma pigmentosum (group C) only repair limited genomic domains, now known to include expressed genes. Hanawalt and his colleagues discovered that repair of some types of damage is selective; active genes are preferentially repaired, and in fact a special repair pathway, termed transcription-coupled repair (TCR), operates on the transcribed strands of expressed genes. TCR was documented in mammalian cells, in E. coli, and in yeast chromosomal and plasmid borne genes.The discovery of TCR in Hanawalt's laboratory has had profound implications for the fields of mutagenesis, environmental carcinogenesis, and risk assessment.

The prototype recQ gene was discovered in E. coli in Hanawalt's laboratory, and we now know of five homologues in humans including the genes mutated in the cancer prone hereditary diseases: Bloom's syndrome, Werners syndrome, and Rothman Thompson syndrome. In E. coli the RecQ helicase was shown to play an important role in the accurate recovery of arrested replication forks.

More recent studies have focused upon the regulation of TCR and the global genomic nucleotide excision repair (GGR) pathway. Features of the TCR pathway (that is defective in Cockayne syndrome) include the possibility of "gratuitous TCR" at transcription pause sites in undamaged DNA. The GGR pathway was shown to be controlled through the SOS stress response in E. coli and through the activated product of the p53 tumor suppressor gene in human cells. These regulatory systems particularly affect the efficiency of repair of the predominant UV-induced photoproduct, the cyclobutane pyrimidine dimer, as well as that of chemical carcinogen DNA adducts, such as benzo(a)pyrene diol-epoxide. Rodent cells (typically lacking the p53-controlled GGR pathway) and tumor virus infected human cells (in which p53 function is abrogated) are unable to carry out efficient GGR of some lesions. Therefore, caution should be exercised in the interpretation of results from such systems for risk assessment in genetic toxicology.

A recent research contribution has been the surprising discovery by Thierry Nouspikel in Hanawalt's laboratory that the attenuated GGR in terminally differentiated human cells, is in fact a consequence of reduced activity of the E1 ubiquitin activating enzyme. Thus, E1 levels control excision repair! This has profound implications for our understanding of DNA repair regulation, and the possibility of modulating the repair response in tumors of patients undergoing chemotherapy.

Current research efforts focus upon naturally occurring non-canonical DNA structures as encumbrances to transcription, and the likelihood of gratuitous TCR. These studies, led by former lab member Silvia Tornaletti (now at University of Florida) and Research Associate Boris Belotserkovskii, have demonstrated that structures such as Z-DNA, H-DNA, G-quartets and PNA-DNA complexes can arrest transcription. A novel method for cancer chemotherapy employing peptide nucleic acid (PNA) for generating a stable R-loop (RNA-DNA hybrid) in a uniquely expressed gene in selected tumor cells is being developed to render the very act of transcription toxic in these cells.

Another area of current research interest is the molecular basis of the DNA repair defects in patients with Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS). Unlike XP, sun-sensitive patients with CS or UVSS do not develop cancers of any type. Graciela Spivak in Hanawalt's group has shown that although both CS and UVSS cells are deficient in TCR of UV-induced DNA damage, only CS cells appear to be defective in the repair of oxidative DNA damage. We hypothesized that the severe developmental and neurological problems in CS may be a consequence of defective processing of endogenous oxidative DNA lesions. An ultrasensitive assay termed “comet-FISH” with single-stranded fluorescent DNA probes was used to examine repair of the prominent oxidative base lesion, 8oxoGuanine (at physiological levels ~100-fold lower than typically studied) by a postdoc, Jia Guo, who along with Spivak and Hanawalt have shown that CS and UVSS cells are equally deficient in TCR of this important lesion.

Last Updated: October 22, 2014
Copyright 1998, Graciela Spivak
email address gspivak at stanford.edu