Max E. Gottesman, PhD

Profile Headshot

Overview

Academic Appointments

  • Charles H. Revson Professor of Biochemistry and Molecular Biophysics and Microbiology and Immunology (in the Institute for Cancer Research)

Administrative Titles

  • Director, Institute for Cancer Research

I was born in 1935 in New York City and grew up there. I have a degree in Philosophy from Swarthmore College and an MD and PhD from Yale University. After a post doc at Rockefeller University, I went to the National Institutes of Health. Except for a year abroad in Paris at the Pasteur Institute, I remained at NIH for 19 years before moving to Columbia University in 1985 to assume the Directorship of the Institute of Cancer research. In addition to writing poetry, I do laboratory research on the genetics of viruses and cancer cells.

Languages

  • French

Credentials & Experience

Education & Training

  • BA, 1956 Philosophy, Swarthmore College
  • MD, 1960 Yale Univ. School of Medicine
  • 1964 Postdoc: Phage genetics, National Institutes of Health
  • PhD, Pharmacology, Yale University

Honors & Awards

1956                              Phi Beta Kappa

1964-1966                     Jane Coffin Child Fund Fellow

1971                              Chairman, Gordon Conference, Biol. Reg. Mech.

1974-1976                     Editorial Advisory Board of Virology

1976-Present                 Editor, Journal of Molecular Biology

1982                              Meritorious Executive Award, NCI

1991                              Division M Lecturer, Amer. Soc. Micro

1991-96                         NIH Board of Scientific Counselors

1991-97                         Chairman, Scientific Counsel of International Laboratory of Biophysics and Genetics

1994-96                         Panel, Human Frontier Scientific Program Review Committee

1996-97                         NCI Prevention Working Group

1996                              Docteur Honoris Causa-Institut National des Science Appliquèes de Lyon, France

1996                              Honorary Doctorate, Peking Union Medical College, Beijing, China

2010                              Fellow, American Academy of Microbiology

2011                              Member, American Academy of Arts and Sciences

2016                              Fellow, American Association for the Advancement of Science

Research

My laboratory investigates the mechanism of transcription termination in E. coli and how termination affects other cellular processes. Blocking the release of a stalled transcription elongation complex leads to clashes with the replisome and the formation of lethal DNA double-strand breaks. Coupling of transcription to translation suppresses stalling.  NusG links RNA polymerase and the first translating ribosome. The linkage is broken by tmRNA, which releases ribosomes at rare codons. The interactions among ribosomes, RNA polymerase and DNA polymerase are being investigated using genetic and biochemical approaches. In addition, the laboratory is probing the structure of the ribosome-NusG-RNA polymerase complex (in collaboration with Dr. J. Frank).

Phage HK022 Nun protein has been an active area of research. We have just begun to understand how Nun interacts with E. coli RNAP to arrest transcription. Nun, however, is full of surprises, and continues to amaze.

We also have a long-standing interest in repair of DNA damage. With Dr. J. Gautier, we defined a replication-independent DNA inter-strand crosslink (ICL) repair pathway in Xenopus oocyte extracts. We have now established an E. coli based system that monitors transcription-coupled repair of ICLs.

Research Interests

  • Regulation of transcription termination in E. coli and bacteriophage
  • Repair of DNA damage in prokaryotes and eukaryotes
  • Hormonal regulation of gene expression
  • phage HK022 Nun transcription termination protein

Grants

DNA REPAIR AND GENOMIC INSTABILITY IN CANCER DEVELOPMENT AND THERAPY (Federal Gov)

Aug 1 2015 - Jul 31 2022

HORMONES: BIOCHEMISTRY AND MOLECULAR BIOLOGY (Federal Gov)

Jul 1 2015 - Jun 30 2020

CORE B (Federal Gov)

Apr 1 2014 - Mar 31 2019

CONTROL OF TRANSCRIPTION TERMINATION IN E. COLI (Federal Gov)

Sep 1 2014 - Aug 31 2018

REGULATION FOR THE DNA DAMAGE RESPONSE BY THE ATM-MRN PATHWAY (Federal Gov)

Jul 1 2001 - May 31 2018

STUDIES OF DNA INTERSTRAND CROSSLINK REPAIR TO IMPROVE CROSSLINKING DRUG THERAPIES (Federal Gov)

Jul 18 2012 - Apr 30 2017

TARGETING OF PROTEIN TYROSINE PHOSPHATASE D1 (PTPD1) IN TREATMENT OF HUMAN BLADDER CANCER (Private)

Aug 1 2013 - Jul 31 2014

HORMONES--BIOCHEMISTRY AND MOLECULAR BIOLOGY (Federal Gov)

Sep 15 1978 - Jun 30 2010

Selected Publications

1. Kim, H.C. and Gottesman, M.E.: (2004) Transcription Termination by Phage HK022 Nun Is Facilitated by C-terminal Lysine Residues.   J. Biol. Chem  279: 13412-7 

2. Feliciello, A., Gottesman, M.E., and Avvedimento, E.V. : (2005) cAMP-PKA signaling to the mitochondria: protein scaffolds, mRNA and phosphatases.  Cellular Signalling   17: 279-287 

3. Kim, H.C., Washburn, R.S, and Gottesman M.E. : (2006) Role of E. coli NusA in Phage HK022 Nun-mediated Transcription Termination.  J. Mol. Biol   359: 10-12 

4. Björn M. Burmann B, Schweimer K, Luo X, Wahl MC, Stitt BL Gottesman ME, and Rösch P: (2010) A NusG:NusE complex links transcription and translation.  Science  (in press)