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BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
Richard Baer
Professor of Pathology & Cell Biology
eRA COMMONS USER NAME (credential, e.g., agency login)
BAERRJ
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
B.A.
1976
Biological Sciences
Ph.D.
1981
Microbiology
Rutgers College, New Brunswick, New Jersey
Rutgers University, New Brunswick, New Jersey
FIELD OF STUDY
A.
Personal Statement
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
20 years, I have studied the role of the BRCA1 tumor suppressor in hereditary breast cancer and genome
stability. With regards to my training experience, I have served on the dissertation committees of over 55
successful Ph.D. candidates, including 12 of my own students, and mentored 22 postdoctoral fellows who are
now pursuing productive careers in biomedical research within academic and industrial settings. Since 2005, I
have also acted as Director of the NCI-sponsored (T32-CA009503) Cancer Biology Training Program for preand postdoctoral trainees in the cancer research laboratories of Columbia University.
B.
Positions, Honors, and Advisory Committees
Positions
1981 - 1987:
1987 - 1990:
1990 - 1995:
1995 - 1999:
1999 - present:
2005 - present:
2007 - present:
Postdoctoral Fellow; MRC-Laboratory of Molecular Biology, Cambridge, UK
Assistant Professor of Microbiology; U.T. Southwestern Medical Center
Associate Professor of Microbiology; U.T. Southwestern Medical Center
Professor of Microbiology; U.T. Southwestern Medical Center, Dallas, TX
Professor of Pathology & Cell Biology; Columbia University Medical Center (CUMC)
Assoc. Director for Basic Science; CUMC Herbert Irving Comprehensive Cancer Center
Deputy Director; CUMC Institute for Cancer Genetics
Honors
1981 - 1982:
1983 - 1985:
1990 - 1992:
1993 - 1997:
Postdoctoral Fellowship; Damon Runyon/Walter Winchell Cancer Fund
Postdoctoral Fellowship; Lady Tata Memorial Trust
Junior Faculty Research Award; American Cancer Society
Faculty Research Award; American Cancer Society
Advisory Committees
1991 - 1993:
Ad Hoc; NIH - Pathology B Study Section
1993 - 1996:
Member; NIH - Pathology B Study Section
2003 - 2004:
Member; DoD Breast Cancer - Molecular Biology and Genetics review panel
2012 - present: Ad Hoc; NIH - Tumor Cell Biology Study Section
2015 – present: Ad Hoc; Komen Breast Cancer Foundation Review Committee
C.
Contributions to Science
1.
Tumor-associated mutations of the c-Myc proto-oncogene in Burkitts’ lymphoma
As a postdoctoral scientist in the laboratory of Dr. Frederick Sanger at the MRC Laboratory of Molecular
Biology (Cambridge, UK) I collaborated with Dr. Terrence Rabbitts in the discovery of tumor-associated
mutations in the translocated alleles of the c-Myc proto-oncogene in Burkitt’s lymphoma. At that time, the
c-Myc translocations had been recently identified, but the mechanisms by which these translocations
activate the malignant potential of c-Myc were not understood. Our findings uncovered two novel
mechanisms of c-Myc activation: 1) mutation of transcriptional control sequences leading to deregulated
c-Myc expression and 2) mutation of coding sequences leading to production of an altered c-Myc protein
product. These results also revealed that juxtaposition of an oncogene adjacent to the immunoglobulin
heavy chain locus renders it susceptible to somatic mutation in a manner analogous to recombined
immunoglobulin variable gene segments. Interestingly, the coding mutations were clustered in a highly
conserved region of c-Myc harboring two potential phosphorylation sites (T58 and S62). Although the
concept of ubiquitin-mediated protein turnover had not yet been defined in the early 1980s, subsequent
studies have shown that these mutations disrupt phospho-dependent control of c-Myc protein stability,
providing a biochemical explanation for the malignant activation of c-Myc by chromosomal translocation.
Rabbitts, T.H., Hamlyn, P.H., and Baer, R. (1983) Altered nucleotide sequence of a translocated c-myc
gene in Burkitt's lymphoma. Nature 306: 760-765.
Rabbitts, T.H., Forster, A., Hamlyn, P., and Baer, R. (1984) Effect of somatic mutation within
translocated c-myc genes in Burkitt's lymphoma. Nature 309: 592-597.
2.
Molecular cloning of chromosome translocations associated with human T cell tumors
After Dr. Sanger’s retirement in 1983, I continued my postdoctoral studies at the MRC in the laboratory of
Dr. Terrence Rabbitts. Around that time, the T cell receptors that mediate immune recognition by
T lymphocytes had been recently discovered. Since tumor-associated chromosome translocations of
B cell malignancies often involve aberrant rearrangements of the immunoglobulin genes, we reasoned
that the chromosome translocations of T cell malignancies would similarly feature rearrangements of the
T cell receptor genes. Therefore, we cloned the T cell receptor / chain locus from human cells and
used it to isolate and characterize the junctions of chromosomal translocation observed in human T cell
lymphomas and leukemias.
Baer, R., Chen, K.C., Smith, S., and Rabbitts, T.H. (1985) Fusion of an immunoglobulin variable gene
and a T-cell receptor constant gene in the chromosome 14 inversion associated with T-cell tumors.
Cell 43: 705-713.
Baer, R., Forster, A., and Rabbitts, T.H. (1987) The mechanism of chromosome 14 inversion in a
human T cell lymphoma. Cell 50: 97-105.
Baer, R., Heppell, A., Taylor, A.M.R., Rabbitts, P.H., Boullier, B., and Rabbitts, T.H. (1987) The
breakpoint of an inversion chromosome 14 in a T cell leukaemia; sequences downstream of the
immunoglobulin heavy chain locus implicated in tumorigenesis. Proc. Natl. Acad. Sci. USA 84: 90699073.
Baer, R., Boehm, T., Yssel, H., Spits, H., and Rabbitts, T.H. (1988) Complex rearrangements within the
human J-C/J-C locus and aberrant recombination between J segments. EMBO J. 7: 1661-1668.
3. Discovery and characterization of the TAL1 and TAL2 proto-oncogenes
In 1987, as an Assistant Professor at UT Southwestern Medical Center in Dallas, I set out to identify the
molecular lesions responsible for T cell acute lymphoblastic leukemia (T-ALL). In the course of this work,
we discovered two proto-oncogenes (TAL1 and TAL2) that are malignantly activated by chromosomal
translocations. Indeed, we found that tumor-specific activation of TAL1, either by chromosomal
rearrangement or ectopic expression, occurs in over 50% of T-ALL patients, establishing TAL1 activation
as the most common genetic lesion associated with this disease. In total, we published over 25 papers
describing the mechanisms of TAL1/2 activation in human T-ALL, as well as the functional and biochemical
properties of their protein products.
Chen, Q., Cheng, J.-T., Tsai, L.-H., Schneider, N., Buchanan, G., Carroll, A., Crist, W., Ozanne, B.,
Siciliano, M.J., and Baer, R. (1990) The tal gene undergoes chromosome translocation in T cell
leukemia and potentially encodes a helix-loop-helix protein. EMBO J. 9: 415-424.
Xia, Y., Brown, L., Yang, C.Y.-C., Tsan, J.T., Siciliano, M.J., Espinosa III, R., Le Beau, M.M. and Baer,
R. (1991) TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T cell
leukemia. Proc. Natl. Acad. Sci. USA 88: 11416-11420.
Wadman, I., Li, J., Bash, R.O., Forster, A., Osada, H., Rabbitts, T.H., and Baer, R. (1994) Specific in
vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J.
13: 4831-4839.
Bash, R.O., Hall, S., Timmons, C.F., Crist, W.M., Amylon, M., Smith, R.G., and Baer, R. (1995) Does
activation of the TAL1 gene occur in a majority of patients with T cell acute lymphoblastic leukemia? A
Pediatric Oncology Group Study. Blood 86: 666-676.
4. Discovery and characterization of the BRCA1/BARD1 heterodimer
When the BRCA1 breast and ovarian cancer susceptibility gene was cloned in 1994, my laboratory set out
to investigate its biological functions and elucidate the mechanisms by which it suppresses tumor
development. Initially, we discovered the BARD1 protein and showed that it exists in vivo as a heterodimer
with BRCA1. We further found that the biochemical, developmental, and tumor suppression functions of
BRCA1 are mediated primarily, if not exclusively, by the BRCA1/BARD1 heterodimer. Through mammaryspecific inactivation of the Brca1 or Bard1 genes, we next developed mouse models of hereditary breast
cancer that faithfully recapitulate the basal-like breast cancers that arise in women who carry germline
BRCA1 mutations. We then used these models to define specific properties of BRCA1 that are (e.g.,
BRCT phospho-recognition) and are not (E3 ligase activity) required for tumor suppression.
Wu, L.C., Wang, Z.W., Tsan, J.T., Spillman, M.A., Phung, A., Xu, X.L., Yang, M.-C.W., Hwang, L.-Y.,
Bowcock, A.M., and Baer, R. (1996) Identification of a RING protein that can interact in vivo with the
BRCA1 gene product. Nature Genetics 14: 430-440.
Laufer, M., Nandula, S.V., Modi, A.P., Wang, S., Jasin, M., Murty, V.V., Ludwig, T., and Baer, R. (2007)
Structural requirements for the BARD1 tumor suppressor in chromosomal stability and homologydirected DNA repair. J. Biol. Chem. 282: 34325-34333. N/A
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: PMC236556593.
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.
PMCID: PMC2365565
5. Discovery and characterization of CtIP as a protein partner of BRCA1
Substantial evidence, including results from our Brca1 mouse breast cancer model, indicate that the
carboxy-terminal (BRCT) domains of BRCA1 are essential for its tumor suppression activity. To ascertain
the mechanism of tumor suppression, we sought to identify factors that associate with these domains in
vivo. In the course of this work, we 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.
Yu, X., Wu, L.C., Bowcock, A.M., Aronheim, A., and Baer, R. (1998) The carboxy-terminal (BRCT)
domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional
repression. J. Biol. Chem. 273: 25388-25392. N/A.
Yu, X. and Baer, R. (2000) Nuclear localization and cell cycle-specific expression of CtIP, a protein that
associates with the BRCA1 tumor suppressor. J. Biol. Chem. 275: 18541-18549. N/A.
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
Reczek, C.R., Szabolcs, M., Stark, J.M., Ludwig, T., and 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. PMCID: PMC3664708
D.
Research Support (current)
1.
NIH/NCI (1R01-CA172272-03). Principal Investigator: Richard Baer
“The BARD1 tumor suppressor and breast cancer”
July 1, 2013 – April 30, 2018
The aims of this proposal are to determine 1) how tumor-associated BARD1 mutations affect functions
of the BRCA1/BARD1 heterodimer and 2) whether BRCT phosphoprotein recognition is required for the
tumor suppression activity of BARD1.
2.
NIH/NCI (5P01-CA097403-10). Principal Investigator: Richard Baer
“Molecular Pathogenesis of Basal-like Breast Cancer”
Project 3. Project Leader: Richard Baer
“The Role of BRCA1/BARD1 in Basal-like Breast Cancer”
September 1, 2009 – August 31, 2015
The Aims of Project 3 are 1) to determine whether the E3 ligase activity of BRCA1/BARD1 is required
for normal development and BRCA1-mediated tumor suppression; 2) to determine whether the E3
ligase activity of BRCA1/BARD1 is required for DSB repair and cell cycle checkpoint control; 3) to
dissect mechanisms of ubiquitin-mediated signaling by BRCA1/BARD1; and 4) examine interactions
between the BRCA1 and PTEN pathways in the development of basal-like breast cancer.
3.
NIH/NCI (1P01CA174653-02). Principal Investigator: Jean Gautier
“DNA double-strand break repair, chromosomes translocations and cancer”
Project 3. Project Leader: Richard Baer
“The role of CtIP in Breast Carcinogenesis”
April 8, 2014 – March 31, 2019
The Aims of Project 4 are to determine 1) how CtIP facilitates breast cancer development, 2) whether
CtIP is required for development of basal-like breast cancer, and 3) whether Ctip is involved in Mycdriven breast cancer.
4.
NIH/NCI (T32-CA09503-28). Principal Investigator: Richard Baer
“Cancer Biology Training Program”
September 1, 2012 – August 31, 2017
This grant is for a training program in cancer research that annually supports 4 predoctoral students
and 4 postdoctoral fellows in laboratories at Columbia University. Dr. Baer’s role is Director of the
Cancer Biology Training Program.
5.
NIH/NCI (5P30-CA013696-39). Principal Investigator: Stephen Emerson
“Cancer Center Support Grant”
July 1, 2014 – June 30, 2019
This grant supports the NIH-designated Herbert Irving Comprehensive Cancer Center (HICCC) at
Columbia University. The HICCC is responsible for the laboratory, clinical, and population-based
cancer research programs and shared resources serving Cancer Center members at Columbia
University Medical Center. Dr. Baer’s role is Associate Director for Basic Science.