Richard J. Baer, PhD
- Professor of Pathology & Cell Biology
I am a Professor of Pathology & Cell Biology at Columbia University Medical Center (CUMC), the Deputy Director of the CUMC Institute for Cancer Genetics, and the Associate Director for Basic Science of the CUMC Herbert Irving Comprehensive Cancer Center. Since 1987, I have maintained an independent program of cancer research that has been supported continuously by R01/P01 grants from the NCI. My independent work was initially focused on the discovery and characterization of TAL1 and TAL2, proto-oncogenes that are malignantly activated in approximately half of patients with T cell acute lymphoblastic leukemia. For the past 15 years, I have studied the role of the BRCA1 tumor suppressor in hereditary breast cancer. In the course of this work, our laboratory discovered the BARD1 protein and showed that the biochemical, developmental, and tumor suppression functions of BRCA1 are mediated primarily by the BRCA1/BARD1 heterodimer. We also identified CtIP as a major interacting partner of BRCA1 and, in collaborative studies, demonstrated the requirements for CtIP in DNA resection, homology-directed repair of DNA double-strand breaks, and cell cycle checkpoint control.
Credentials & Experience
Honors & Awards
1981-1982 Postdoctoral Fellowship; Damon Runyon/Walter Winchell Cancer Fund
1983-1985 Postdoctoral Fellowship; Lady Tata Memorial Trust
1990-1992 Junior Faculty Research Award; American Cancer Society
1993-1997 Faculty Research Award; American Cancer Society
Germline mutations of the BRCA1 gene are a major cause of hereditary breast and ovarian cancer. Woman who carry BRCA1 mutations often develop basal-like breast tumors, an especially lethal form of breast cancer for which there are currently no effective targeted therapies. Thus, an important priority of current research is to determine the mechanisms by which BRCA1 suppresses tumor formation in normal mammary epithelial cells and how these mechanisms are disrupted in BRCA1 mutation carriers. Significantly, the protein product of BRCA1 has been implicated in multiple aspects of the DNA damage response, including homology-directed repair of double-strand DNA breaks, stalled replication fork stability, DNA inter-strand crosslink repair, and cell cycle checkpoint control. To understand the role of BRCA1 in these processes, we study the BRCA1 pathway at the biochemical, cellular, and organismal levels. In doing so, we have identified novel components of the pathway, including the BARD1 and CtIP proteins, and we are now characterizing how the various components of the BRCA1 pathway promote genome stability and tumor suppression.
- The pathogenesis of hereditary breast cancer
RESTORING GENOME STABILITY AND TUMOR SUPPRESSION IN BRCA1 DEFICIENT CELLS (Federal Gov)
Jan 1 2019 - Dec 31 2022
BONE AND BREAST CANCER MOLECULAR INTERACTIONS (Federal Gov)
Dec 1 2015 - Nov 30 2020
DNA DOUBLE-STRAND BREAK REPAIR, CHROMOSOMES TRANSLOCATIONS AND CANCER (Federal Gov)
Apr 1 2014 - Mar 31 2020
IMPACT OF DNA BREAK REPAIR AND CHROMOSOMAL REARRANGEMENTS ON BREAST CANCER (Private)
Oct 3 2016 - Oct 2 2019
CANCER CENTER SUPPORT GRANT (Federal Gov)
Jul 1 2014 - Jun 30 2019
THE BARD1 TUMOR SUPPRESSOR AND BREAST CANCER (Federal Gov)
Jul 1 2013 - Apr 30 2018
CANCER BIOLOGY TRAINING GRANT (Federal Gov)
Sep 1 1984 - Aug 31 2017
MOLECULAR PATHOGENESIS OF BASAL-LIKE BREAST CANCER (Federal Gov)
Jul 1 2002 - Aug 31 2015
WHICH FUNCTIONS OF BRCA1 SUPPRESS BREAST CANCER? (Private)
Jul 1 2010 - Jun 30 2012
THE ROLE OF CTIP IN BRCA1-MEDIATED TUMOR SUPPRESSION (Federal Gov)
Feb 1 2009 - Jan 31 2012
THE ROLE OF BRCA1/BARD1 IN BASAL-LIKE BREAST CANCER (Federal Gov)
Jun 15 2009 - Apr 30 2011
Sartori, A.A., Lukas, C., Coates, J., Fu, S., Baer, R., Lukas, J., and Jackson, S.P. (2007) CtIP cooperates with the MRE11 complex to promote DNA end resection. Nature 450: 509-514. PMCID: PMC2409435
Dupré, A., Boyer-Chatenet, L., Sattler, R.S., Modi, A.P., Lee J.-H., Nicolette M.L., Kopelovich, L., Jasin, M., Baer, R., Paull, T.T., and Gautier, J. (2007) Identification and characterization of an inhibitor of the MRE11-RAD50-NBS1 complex. Nature Chemical Biology 4: 119-125. PMCID: PMC3065498
Shakya, R., Szabolcs, M., McCarthy, E.E., Ospina, E., Basso, K., Nandula, S.V., Murty, V.V., Baer, R., and Ludwig, T. (2008) A common basal-like phenotype for mammary carcinomas induced by conditional inactivation of the BARD1 and BRCA1 tumor suppressors. Proc. Natl. Acad. Sci. USA 105: 7040-7045. PMCID: PMC2365565
Reid, L.J., Shakya, R., Modi, A.P., Lokshin, M., Cheng, J.-T., Jasin, M., Baer, R., and Ludwig, T. (2008) The E3 ubiquitin ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks. Proc. Natl. Acad. Sci. 105: 20876–20881. PMCID: PMC2603436
Wu-Baer, F., Ludwig, T., and Baer, R. (2010) The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. Mol. Cell. Biol. 30: 2787-2798. PMCID: PMC2876507
Peterson, S.E., Li, Y., Chait, B.T., Gottesman, M.E., Baer, R., and Gautier, J. (2011) Cdk1 uncouples CtIP-dependent resection and Rad51 filament formation during M-phase double-strand break repair. J. Cell Biol. 194: 705-720. PMCID: PMC3171114
Shakya, R., Reid, L.J., Reczek, C.R., Cole, F., Egli, D., Lin, C.-S., deRooij, D.G., Hirsch, S., Ravi, K., Hicks, J.B., Szabolcs, M., Jasin, M., Baer, R., and Ludwig, T. (2011) BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science 334: 525-528.
Li T, Kon N, Jiang L, Tan M, Ludwig T, ZHao Y, Baer R, Gu W. (2012) Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell, 146:1269-83.
Peterson SE, Li Y, Wu-Baer F, Chait BT, Baer R, Yan H, Gottesman ME, Gautier J. (2013) Activation of DSB processing requires phosphorylation of CtIP by ATR. Mol. Cell, 49:657-67.
Baer R. (2013) Luring BRCA1 to the scene of the crime. Cancer Cell, 23:565-7.
Reczek CR, Szabolcs M, Start JM, Ludwig T, Baer R. (2013) The interaction between CtIP and BRCA1 is not essential for resection-mediated DNA repair or tumor suppression. J. Cell Biol. 201:693-707.
Aparicio T, Baer R, Gautier J. DNA double-strand break repair pathway choice and cancerDNA Repair (Amst). 2014 Apr 16. pii: S1568-7864(14)00085-8.