Faculty and Staff
Nutritional and Metabolic Doctoral Training Faculty
Richard Baer, Ph.D.
Professor of Pathology
B.A. 1976, Rutgers University
Ph.D. 1981, Rutgers University
Hereditary breast cancer poses a major health risk due to its prevalence and the severity of its clinical manifestations. Genetic studies have established that germline mutations in the BRCA1 tumor susceptibility gene are the major cause of this disease. The main focus of Dr. Baer's research program is to elucidated the normal biological functions of the BRCA1 protein and to determine why loss of these functions predisposes women to breast cancer. To investigate the biochemical functions of its protein product, they initially sought to define the cellular factors that associate with BRCA1 in vivo. This work led to the identification of two novel interacting polypeptides: the BRCA1-associated RING domain (BARD1) protein and the C-terminal interacting protein (CtIP). Subsequent studies have shown that BARD1 is an especially important factor in BRCA1-mediated tumor suppression. The BARD1 protein is structurally related to BRCA1 in that it harbors an N-terminal RING domain and two tandem C-terminal BRCT motifs. Moreover, most, if not all, of the cellular pool of BRCA1 polypeptides exist in the form of a heterodimer with BARD1, and mutations of the BARD1 gene are observed in rare cases of breast, ovarian and endometrial carcinoma. Together, these observations suggest that the BRCA1/BARD1 heterodimer is the physiological mediator of BRCA1 functions. Indeed, recent biochemical studies indicate that the heterodimer serves as a potent ubiquitin E3 ligase and that this enzymatic activity is ablated by tumor-associated missense mutations in the BRCA1 motif. To gain further insights into the mechanism of BRCA1-mediated tumor suppression, Dr. Baer's laboratory is currently seeking the enzymatic substrates of the BRCA1/BARD1 heterodimer and examining its role in the DNA damage response. Dr. Baer's group has also begam exploring the role of retinoid signaling in the regulation of breast cancer genes and their interacting protein genes and, in collaboration with Dr. Thomas Ludwig, in normal mammary gland development.
Recent Publications - Pubmed
Wu-Baer, F., Lagrazon, K., Yuan, W., Baer, R. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. J Bio Chem 278:34743-34746, 2003.
Li, M., Brooks, C.L., Wu-Baer, F., Chen, D., Baer, R., Gu, W. Mono- vs. polyubiquitination: differential control of p53 fate by MDM2. Science 302:1972-1975, 2003.
Choudhury, A.D., Xu, H., Baer, R. Ubiquitination and proteasomal degradation of the BRCA1 tumor suppressor is regulated during cell cycle progression. J Biol Chem 279:33909-33918, 2004.