Martin L. Privalsky

image of Martin L. Privalsky

Professor

Departments

Microbiology and Molecular Genetics

Offices and Labs

247 Briggs Hall
752-3013

Degrees

1979 PhD Biochemistry University of California, Berkeley
1974 BS Biochemistry State University of New York, Stony Brook
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)
UC Davis Distingushed Professr (2012)

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

ProfessionalSocieties

Endocrinology Society
American Diabetes Association

CBS Grad Group Affiliations

Biochemistry, Molecular, Cellular and Developmental Biology
Integrated Genetics and Genomics

Specialties / Focus

Integrated Genetics and Genomics
  • Chromosome Biology
Biochemistry, Molecular, Cellular and Developmental Biology
  • Molecular Medicine

Graduate Groups not Housed in CBS

Pharmacology and Toxicology
Microbiology

Labs

Room 247 Briggs Hall website
  • Michael Goodson, Robyn Jimenez, Liming Liu, Brenda Mengeling, Amy Schroeder, Chelsea Snyder

Teaching Interests

Recombinant DNA. Molecular and Cellular Biology. Transcriptional Regulation. Oncogenes. Cell Regulation.

Courses

MIC 175 Cancer Biology (Spring)
BIS 104 Regulation of Cell Function
MIC 215 Recombinant DNA Techniques
MCB 263 Biotechnology Fundamentals and Application

Publications

3/3/2017 7:46:40 AM
  • Jimenez R, Privalsky ML. 2016. A Resistance to Thyroid Hormone Syndrome mutant operates through the target gene repertoire of the wild-type thyroid hormone receptor.  Molecular and Cellular Endocrinology.  In press.

  • Privalsky ML, Snyder CA, Goodson ML. 2016.  Corepressor diversification by alternative mRNA splicing is species specific.  BMC Evolutionary Biology 16, 221-234.

  • Snyder CA, Goodson ML, Schroeder AC, Privalsky ML. 2015. Regulation of corepressor alternative mRNA splicing by hormonal and metabolic signaling. Molecular and Cellular Endocrinology 413, 228-235.

  • Goodson ML, Young BM, Snyder CA, Schroeder AC, Privalsky ML. 2014. Alteration of NCoR corepressor splicing in mice causes increased body weight and hepatosteatosis without glucose intolerance.  Molecular and Cellular Biology 34, 4104-4114.

  • Schroeder A, Jimenez R, Young BM, Privalsky ML. 2014. The ability of thyroid hormone receptors to sense T4 as an agonist depends on receptor isoform and on cellular cofactors. Molecular Endocrinology 28, 745-757.

  • Schroeder AC, Privalsky ML. 2014. Thyroid hormones, T3 and T4, in the brain. Frontiers of Endocrinology (Lausanne). 5, 40-46.

  • Hahm JB, Schroeder AC, Privalsky ML. 2014. The two major isoforms of thyroid hormone receptor, TR-alpha 1and TR-beta 1, preferentially partner with distinct panels of auxiliary proteins. Molecular and      Cellular Endocrinology 383, 80-95.

  • Zota AR, Linderholm L, Park JS, PetreasM, Guo T, Privalsky ML, Zoeller RT, Woodruff TJ, 2013. A temporal comparison of PBDEs, OH-PBDEs, PCBs, and OH-PCBs in the serum of second trimester pregnant women recruited from San Francisco General      Hospital, California. Environmental Science and Technology. 48, 2512-2513.

  • Hahm JB, Privalsky ML. 2013.  Research Resource: Identification of novel coregulators specific for thyroid hormone receptor-beta 2. Molecular Endocrinology, 27, 840-859.

  • Sinha RA. You SH, Zhou J, Siddique MM, Bay BH, Zhu X, Privalsky ML, Cheng SY, Stevens RD, Summers SA, Newgard CB, Lazar MA, Yen PM. 2012. Thyroid hormone stimulates lipid catabolism via activation of autophagy. Journal of Clinical Investigation 122, 2428-2438.
  • Mengeling BJ, Goodson ML, Bourguet W, Privalsky ML. 2012. SMRTelpsilon, a corepressor variant that interacts with a unique subset of nuclear receptors and displays a high specificity for retinoic acid receptors. Molecular and Cellular Endocrinology 351, 306-316.
  • Goodson ML, Mengeling BJ, Jonas BA, Privalsky ML. 2011. Alternative mRNA splicing of corepressors generates variants that play opposing roles in adipocyte differentiation. Journal of Biological Chemistry 286, 44988-44999.
  • Lee SH, Young BM, Wei W, Chan IH, Privalsky ML. 2011. A mechanism for Pituitary-Resistance to Thyroid Hormone (PRTH) Syndrome: a loss in cooperative coactivator contacts by thyroid hormone receptor (TR)β2. Molecular Endocrinology 25, 1111-1125.
  • Rosen MD, Chan IH, Privalsky ML. Mutant thyroid hormone receptors (TRs) isolated from distinct cancer types display distinct target gene specificities: a unique regulatory repertoire associated with renal clear cell carcinomas. Molecular Endocrinology 23, 1183-1192.
  • Rosen MD, Privalsky ML, 2011. Thyroid hormone receptor mutations in cancer and resistance to thyroid hormone: perspective and prognosis. Journal of Thyroid Research Volume 2011 (2011), doi:10.4061/2011/361304
  • Varlakhanova N, Hahm J, Privalsky ML. 2011. Regulation of SMRT corepressor dimerization and composition by MAP kinase phosphorylation. Molecular and Cellular Endocrinology 332, 180-188.
  • Mengeling BJ, Phan TQ, Goodson ML, Privalsky ML. 2011. Aberrant corepressor interactions implicated in PML-RARα and PLZF-RARα leukemogenesis reflect an altered recruitment and release of specific NCoR and SMRT splice variants. Journal of Biological Chemistry 286, 4236-4347
  • Varlakhanova N, Snyder C, Jose S, Hahm JB, Privalsky ML. 2010. Estrogen receptors recruit. SMRT and N-CoR corepressors through newly recognized contacts between the corepressor N-terminus and the receptor DNA binding domain. Molecular and Cellular Biology 30, 1434-1445.
  • Phan TQ, Jow MM, Privalsky ML. 2010. DNA recognition by thyroid hormone and retinoic acid receptors: 3-4-5 rule modified. Molecular and Cellular Endocrinology 319, 88-98.
  • Chan IH, Privalsky ML. 2010. 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 8,15-23.
  • Chan IH, Privalsky ML. 2009. Thyroid hormone receptor (TR) mutants implicated in human hepatocellular carcinoma display an altered target gene repertoire. Oncogene 28, 4162-4174.
  • 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 23, 1758-1775.
  • 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. Journal of Biological Chemistry 280, 7493-7503.
  • Lee S, Privalsky ML. 2005. Heterodimers of retinioc acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties. Molecular Endocrinology 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. Molecular Endocrinology 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. Molecular Endocrinology 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. Journal of Biological Chemistry 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 Endocrinology 18, 2839-2853.