Martin L. Privalsky
Professor
mlprivalsky@ucdavis.edu

Microbiology

Office
247 Briggs Hall
752-3013


Picture of Martin L. Privalsky
 
Degrees:
1979 PhD University of California, Berkeley Biochemistry
1974 BS State University of New York, Stony Brook Biochemistry
Postdoctoral Research - University of California, San Francisco - J. Michael Bishop Laboratory
Research Interests:

Our research focuses on understanding how cells regulate their proliferation and differentiation and the aberrant events which lead to neoplasia. Our specific goal is a better understanding of the actions of the nuclear receptors (also known as nuclear hormone receptors) in normal cells and in disease. Nuclear receptors are a family of hormone-regulated transcription factors, and include the steroid, retinoid, and thyroid hormone receptors; collectively they play critical roles in vertebrate homeostasis, differentiation, and reproduction. Nuclear receptors bind to specific target genes and modulate gene expression in response to hormones of extracellular origin, Intriguingly, these receptors can either repress or activate transcription by recruiting partner proteins denoted corepressors and coactivators. An alpha-helical domain (helix 12) at the C-terminus of these receptors functions as a hormone-regulated “molecular toggle switch;” by altering its conformation, helix 12 determines whether a corepressor or a coactivator is recruited to the nuclear receptor. Notably, defects in the operation of the helix 12 toggle switch result in aberrant corepressor and coactivator acquisition and, as a result, human disease (including both endocrine and neoplastic disorders). Our research seeks to employ these aberrant receptors as tools to determine the molecular pathways that operate in human diseases and to elucidate the actions of the normal receptors in the normal cell. We are currently investigating the contributions of nuclear receptor function in normal adipose cell differentiation, in thyroid hormone resistance, in leukemia, and in renal clear cell and hepatocellular carcinomas.
Awards:
National Institutes of Health/NCI MERIT Award
U. C. Davis Biochemistry and Molecular Biology Graduate Teaching Award (2000)
Department and Center Affiliations:
National Institutes of Health/UC Davis Molecular and Cellular Biology Training Grant
UC Davis Cancer Center
National Institutes of Health/UC Davis Oncogenic Signals and Chromosome Biology Training Grant
Department of Molecular and Cellular Biology- secondary membership
Professional Societies:
Endocrinology Society
American Society for Microbiology
American Association for Cancer Research
CBS Graduate Group Affiliations:
Biochemistry, Molecular, Cellular and Developmental Biology  
Genetics  
Graduate Groups not Housed in CBS:
Pharmacology and Toxicology  
Microbiology  
Publications: Last updated 11/20/2009
  • Chan IH, Privalsky ML. 2009. A conserved lysine in the thyroid hormone receptor (TR)-alpha1 DNA binding domain, mutated in hepatocellular carcinoma, serves as a sensor for transcriptional regulation. Molecular Cancer Research. In press.
  • Phan TQ, Jow MM, Privalsky ML. 2009. DNA recognition by thyroid hormone and retinoic acid receptors: 3-4-5- rule modified. Molecular and Cellular Endocrinology. In press.
  • Chan IH, Privalsky ML. 2009. Thyroid hormone receptor (TR) mutants implicated in human hepatocellular carcinoma display an altered target gene repertoire. Oncogene. In press.(available as preprint on line at Oncogene as doi: 10.1038/onc.2009.26).
  • Chan IH, Privalsky ML. 2009, Isoform specific transcriptional activity of overlapping target genes that respond to thyroid hormone receptors alpha 1 and beta 1. Molecular Endocrinology. In press (Rapid Electronics Publication availabl as doi:10.1210/me.2009-0025).
  • Rosen MD, Privalsky ML. 2009. Thyroid hormone receptor mutations found in renal clear cell carcinomas alter corepressor release and reveal helix 12 as key determinant of corepressor specificity. Molecular Endocrinology 23, 1183-1192.
  • Privalsky ML, Lee SH, Hahm JB, Young BM, Fong, RNG, Chan IH. 2009. The p160 coactivator PAS-B motif stabilized nuclear receptor binding and contributes to isoform-specific regulation by thyroid hormone receptors. Journal of Biological Chemistry, 284, 19554-19563
  • Chen IH, Browosky, AD, Privalsky ML. 2008 A cautionary note as to the use of pBI-L and related luciferase vector in the study of thyroid endocrinology. Thyroid 18, 665-666.
  • Goodson ML, Farboud B, Privalsky ML. 2008. High throughput analysis of nuclear receptor-cofactor interactions. pg. 157-170, in Methods in Molecular Biology: Nuclear Receptor Superfamily. McEwan IJ, Ed. Humana Press, New York.
  • Privalsky, ML. 2008. Thyroid hormone receptors, coregulators, and disease. Chapter 6. in Nuclear Receptor Coregulators and Human Disease (R. Kumar and B. O’Malley, eds.). World Scientific Publishing. London, Great Britain.
  • Jonas, BA, Varlakhanova N, Hayakawa F, Goodson MG, and Privalsky, ML. 2007. Response of SMRT and N-CoR corepressors to MAP Kinase Kinase Kinase cascades is determined by alternative mRNA splicing. Molecular Endocrinology 21, 1924-1929.
  • Mengeling BJ, Lee SH, and Privalsky ML. 2007. Coactivator recruitment is enhanced by thyroid hormone receptor trimers, Molecular and Cellular Endocrinology. 280, 47-62.
  • Chan, IV, Privalsky ML. 2006. Thyroid hormone receptors mutated in liver cancer function as distorted antimorphs. Oncogene 25, 3576-3588.
  • Goodson ML, Jonas BA, Privalsky, ML. 2006. Corepressors: custom tailoring while you wait. (an invited review). Nuclear Receptor Signaling 3, e003.
  • Goodson ML, Jonas BA, Privalsky ML. 2005. Alternative mRNA splicing of SMRT creates functional diversity by generating corepressor isoforms with different affinities for different nuclear receptors. J Biol Chem, 280, 7493-7503.
  • Lee S, Privalsky ML. 2005. Heterodimers of retinioc acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties. Mol Endocrinol 19, 863-878.
  • Mengeling BJ, Pan F, Privalsky ML. 2005. Novel mode of DNA recognition by thyroid hormone receptors: TR{beta}-isoforms can bind as trimers to natural response elements comprised of reiterated half-sites. Mol Endocrinol. 19, 35-51.
  • Wan W, Farboud B, Privalsky ML. 2005. Pituitary resistance to thyroid hormone (RTH)-syndrome is associated with T3 receptors that selectively impair beta2 isoform function. Mol Endocrinol 19, 1529-1542.
  • Lee SH, Privalsky ML. 2005. Multiple mutations contribute to repression by the v-Erb A oncoprotein. Oncogene. Oncogene 24, 6737-6752.
  • Privalsky ML. 2004. The role of corepressors in transcriptional regulation by nuclear hormone receptors. Annual Review of Physiology 66:315-360.
  • Hayakawa F and Privalsky ML. 2004. Phosphorylaton of PML by mitogen-activated protein (MAP) kinases plays a key role in arsenic trioxide-mediated apoptosis. Cancer Cell. 5, 389-401.
  • Jonas B, Privalsky ML. 2004. SMRT and N-CoR corepressors are regulated by distinct kinase signaling pathways. J Biol Chem 279, 54676-54686.
  • Farboud B and Privalsky ML. 2004. Retinoic acid receptor-alpha is stabilized in a repressive state by its C-terminal, isotype-specific F domain. Molecular Endocrinol 18, 2839-2853.
  • Hong S-H, Privalsky ML. 2001. Arsenic trioxide is a potent inhibitor of the interaction of SMRT corepressor with its transcription factor partners, including the PML-RARa oncoprotein found in human acute promyelocytic leukemia. Molecular and Cellular Biology 21, 7172-82.
  • Privalsky ML. 2003. Activation incarnate. Developmental Cell 5: 1-9.
  • Farboud B, Hauksdottir H, Wu Y, and Privalsky ML. 2003. Isotype-restricted corepressor recruitment: a constitutively-closed helix 12 conformation in retinoic acid receptors beta and gamma interferes with corepressor recruitment and prevents transcriptional repression. Molecular and Cellular Biology 23: 2844-2858.
Laboratory Personnel:
Room 247 Briggs Hall
http://www.mic.ucdavis.edu/privalsky/
Michael Goodson, Johnnie Hahm, Liming Liu, Brenda Mengeling, Meghan Rosen, Chelsea Snyder, Briana Young

Teaching Interests:
Recombinant DNA. Molecular and Cellular Biology. Transcriptional Regulation. Oncogenes. Cell Regulation.
Courses:
BIS 104 Regulation of Cell Function
MIC 215 Recombinant DNA Techniques
MCB 221C Molecular Biology
MCB 221D Cellular Biochemistry
MCB 295 Oncogenes, Retroviruses, and Cell Regulation Journal Club
MCB 263 Biotechnology Fundamentals and Application