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Rodney J. Rothstein, PhD

  • Professor of Genetics & Development
Rodney J. Rothstein, PhD
By using budding yeast as an experimental organism, we are able to study essential biological processes such as the mechanisms underlying the recognition and repair of DNA damage. The role that genetic recombination plays during repair is an integral part of our research. We are exploring the biological response to DNA damage by studying a central recombination protein, Rad52, a ribonuclease reductase inhibitor that responds degrades after DNA damage, Sml1, and a topoisomerase helicase complex necessary for resistance to DNA damaging agents, Top3/Sgs1. The availability of a complete gene disruption library is another tool that aids our research. By developing methods to enhance the utility of this resource, we are facilitating genome-wide analysis of not only budding yeast, but other species as well.

Models for double-strand DNA break repair, genome stability and gene overexpression in cancer cells. Since DNA repair is essential for preserving genome integrity in all organisms, it is not surprising that the cellular pathways that mediate DNA repair are highly conserved. My laboratory primarily focuses on the biological responses to DNA damage. We use budding yeast as a model system and are particularly interested in uncovering the genes and pathways involved in the repair of DNA double-strand breaks and DNA crosslinks. Using fluorescently tagged proteins, we have developed yeast strains that allow us to follow events from the initiation of the damage to its repair. These strains allow us to study the movement of chromosomes to determine their spatiotemporal relationships during the DNA damage response. The lab is also particularly interested in using yeast as a model to study cancer and cancer predisposition. This approach allows the power of yeast genetic screens to be exploited to understand genetic interactions in cancer cells. We are especially interested in gene overexpression, an underexploited area of cancer biology. The pathways that we identify in yeast are often conserved in mammalian cells. Thus, the laboratory also studies the mammalian orthologs of the yeast genes that we identify to evaluate their functional status in human tumors. Our goal is anti-cancer therapeutic target discovery. To this end, we have on-going collaborations with other members of the Cancer Center, including Alberto Ciccia, Dawn Hershman and Gary Schwartz to exploit our yeast finding in mammalian cells. In addition to research, I am committed to the training of students and the mentoring of post-docs. For the past 31 years at Columbia University Medical Center, I have trained 19 PhD students (4 more in progress) and 22 post-docs, many of whom are professors at various stages in their careers. Some are involved in the biotechnology industry, patent law or science filmmaking. More than 30 undergraduates have passed through the lab on their way to graduate or medical school. I have also served on numerous training committees and thesis exams (over 60). Finally, I am the course director of “Genetic Approaches to Biological Problems” for the past 33 years, which is required for all first year Genetics & Development students. In 2012, I was nominated by the graduate students for the Columbia University Presidential Faculty Teaching Award, for which I was one of 10 finalists from over 600 nominated university-wide.

Yeast genetic and cell biological approaches to understand the cellular response to DNA damage & the mechanisms of genetic recombination; Genomic approaches to understand the control of genome stability in yeast as well as normal & cancer cells.

Departments and Divisions

  • Department of Genetics & Development

Centers/Institutes/Programs

  • Herbert Irving Comprehensive Cancer Center

NIH Grants

  • MOLECULAR MECHANISMS UNDERLYING DNA DOUBLE-STRAND BREAK AND CROSSLINK REPAIR (Federal Gov)

    Jul 1 2016 - Aug 31 2021

    CENTERS FOR CANCER SYSTEMS THERAPEUTICS (CAST) (Federal Gov)

    Aug 8 2016 - Jul 31 2021

    MECHANISM OF SPONTANEOUS AND DSB-INDUCED REPAIR (Federal Gov)

    Sep 1 2015 - Aug 31 2019

    YEAST CHROMATIN STRUCTURE AND FUNCTION (Federal Gov)

    Jan 1 2015 - Dec 31 2018

    GENETICS OF THE FORMATION OF REPAIR & RECOMBINATION FOCI (Federal Gov)

    Jan 1 2003 - Feb 29 2016

    DEVELOPING A NEW PARADIGM TO DISCOVER NOVEL BREAST CANCER DRUG TARGETS (NY State Gov)

    Sep 1 2013 - Aug 31 2015

    IN VIVO CHOREOGRAPHY OF DNA MOLECULES AND REPAIR PROTEINS DU RING SEARCH FOR HOMOLOGY (Private)

    Jan 1 2010 - Dec 31 2011

    MECHANISTIC INSIGHTS INTO THE SHU COMPLEX AND SGS1 IN DNA RE PAIR AND REPLICATION (Federal Gov)

    Aug 1 2009 - Jun 30 2011

Publications

1. Reid, R.J.D., González-Barrera, S., Sunjevaric, I., Alvaro, D., Ciccone, S., Wagner, M. and Rothstein, R.: (2011) Selective ploidy ablation, a high-throughput plasmid transfer protocol, identifies new genes affecting topoisomerase I–induced DNA damage.  Genome Research  21: 477-486 

2. Miné-Hattab, J. and Rothstein, R.: (2012) Increased chromosome mobility facilitates homology search during recombination.  Nature Cell Biol  14: 510–517 

3. Dittmar, J.C., Pierce, S., Rothstein, R. and Reid, R.J.D. : (2013) Physical and genetic interaction density reveals functional organization and informs significance cutoffs in genome-wide screens.   Proc Natl Acad Sci USA  110: 7389-7394 

4. Symington, L.S., Rothstein, R. and Lisby, M. : (2014) Mechanisms and regulation of mitotic recombination in Saccharomyces cerevisiae.  Genetics  198: 795-835 

5. Lisby, M. and Rothstein, R.: (2015) Cell biology of mitotic recombination.  Cold Spring Harb Perspect Biol   7: a016535 

6. Reid, RJD, Du, X, Sunjevaric, I, Rayannavar, V, Dittmar, J, Bryant, E, Maurer, M, Rothstein, R. : (2016) A synthetic dosage lethal genetic interaction between CKS1B and PLK1 is conserved in yeast and human cancer cells..  Genetics  204: 807-819