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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 Awards: National Institutes of Health/NCI MERIT Award U. C. Davis Biochemistry and Molecular Biology Graduate Teaching Award (2000) Department and Center Affiliations: Department of Molecular and Cellular Biology- secondary membership 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 Professional Societies: Endocrinology Society American Society for Microbiology American Association for Cancer Research Grad Group Affiliations and Specialties: Biochemistry and Molecular Biology Genetics Microbiology Non-DBS Grad Group(s) - Pharmacology and Toxicology Publications: Chan IH, Privalsky ML. 2009. Thyroid hormone receptor (TR) mutants implicated in human hepatocellular carcinoma display an altered target gene repertoire. Oncogene. In press. 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 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. 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. Mengeling BJ, Lee SH, and Privalsky ML. 2007. Coactivator recruitment is enhanced by thyroid hormone receptor trimers, Molecular and Cellular Endocrinology. 280, 47-62. 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. Goodson ML, Jonas BA, Privalsky, ML. 2006. Corepressors: custom tailoring while you wait. (an invited review). Nuclear Receptor Signaling 3, e003. Chan, IV, Privalsky ML. 2006. Thyroid hormone receptors mutated in liver cancer function as distorted antimorphs. Oncogene 25, 3576-3588. Lee s, Privalsky ML. 2005. Multiple mutations contribute to repression by the v-Erb A oncoprotein. Oncogene. Oncogene 24, 6737-6752. 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 S, Privalsky ML. 2005. Heterodimers of retinioc acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties. Mol Endocrinol 19, 863-878. 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. 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. 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. Jonas B, Privalsky ML. 2004. SMRT and N-CoR corepressors are regulated by distinct kinase signaling pathways. J Biol Chem 279, 54676-54686. 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. Privalsky ML. 2004. The role of corepressors in transcriptional regulation by nuclear hormone receptors. Annual Review of Physiology 66:315-360. 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. Yoh SM and Privalsky ML. 2001. Transcriptional repression by thyroid hormone receptors: a role for receptor homodimers in the recruitment of SMRT corepressor. Journal of Biological Chemistry. 276:16857-16867 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. 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 a-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. Laboratory Personnel: Room 247 Briggs Hall - Ivan Chan, Michael Goodson, Meghan Dukerich, Johnnie Hahm, Liming Liu, Brenda Mengeling, Teri Phan, Chelsea Snyder, Briana Young http://www.mic.ucdavis.edu/privalsky/ Teaching Interests:Recombinant DNA. Molecular and Cellular Biology. Transcriptional Regulation. Oncogenes. Cell Regulation. Courses Taught: BIS 104 Regulation of Cell Function MIC 215 Recombinant DNA Techniques MCB 295 Oncogenes, Retroviruses, and Cell Regulation Journal Club MCB 263 Biotechnology Fundamentals and Application |
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