Present Position:
Professor
Section of Microbiology
and Section of Molecular and Cellular Biology
Division of Biological Sciences
University of California at Davis
July 1, 1992 to present time
Summary of Research Interests: My general interest is in the
mechanisms by which proliferation and differentiation is regulated in
normal cells, and in the abnormal processes that occur in neoplasia. My
specific goal is a better understanding of the actions of the nuclear
hormone receptors in normal cells and in oncogenesis. Nuclear hormone
receptors are a family of ligand-regulated transcription factors, and
include the steroid, retinoid, and thyroid hormone receptors. These
receptors directly modulate gene expression in response to hormones of
extracellular origin, and play critical roles in metazoan homeostasis,
differentiation, and reproduction. In addition, aberrant nuclear hormone
receptors have been implicated as causal or contributory factors in a
variety of human and non-human cancers. My research seeks to exploit these
aberrant oncogenic receptors, both to better elucidate the actions of
their normal counterparts, and to determine the molecular pathways that
operate in neoplasia.
Previous Positions:
Associate Professor
Department of Microbiology
University of California at Davis
July 1988 to July 1992
Assistant Professor
Department of Bacteriology (former name of department)
University of California at Davis
April, l984 to June, l988
Assistant Research Virologist
University of California at Davis
Dr. J. Michael Bishop's Laboratory
Department of Microbiology and Immunology and
The George Hooper Foundation
University of California at San Francisco
June l983 to April l984
Research Scientist
Chiron Corporation
Emeryville, California 94608
January l983 to May l983
Education and Degrees:
Post-doctoral (1979-1983): J. Michael Bishop Laboratory
Department of Microbiology
University of California at San Francisco
Ph. D. (1974-1979): Department of Biochemistry
Edward E. Penhoet, thesis advisor
University of California at Berkeley
B. S. (1970-1974): Department of Biochemistry
State University of New York at Stony Brook
Research Experience:
April 1984 to present: Signal transduction and transcriptional
regulation in normal and neoplastic cells. Understanding the roles of the
erb A oncogene protein (thyroid hormone receptor), retinoic acid
receptors, and related transcription factors in normal cells and in
neoplastic transformation.
January 1983 to May 1983: Scientist with the Chiron Corporation,
developing a recombinant DNA vaccine for hepatitis A.
October 1979 to December 1982 and June 1983 to April 1984:
Researcher with Dr. J. Michael Bishop (U.C.S.F.), identifying and
characterizing proteins involved in oncogenesis by avian erythroblastosis
virus.
March 1975 to September 1979: Ph.D. thesis with Dr. Edward E.
Penhoet (U.C. Berkeley), studying the synthesis and post-translational
modification of influenza viral proteins.
January 1973 to May 1974: Undergraduate research project with
Dr. Vincent P. Cirillo (S.U.N.Y. Stony Brook) investigating membrane
transport in mycoplasma and in yeast.
Professional Service:
Served as a member, National Science Foundation Eukaryotic Genetics
Study Panel (1989-1990), Ad hoc member, National Institutes of
Health Molecular Biology Study Section (1992) and Virology Study Section
(1994).
Ad hoc reviewer on USDA grants and N.I.H. site visit committees.
Member of the Editorial Board of Archives of Biochemistry and
Biophysics. Served as an ad hoc reviewer for the journals Molecular
and Cellular Biology, Science, Journal of Biological Chemistry,
Journal of Cell Biology, Proceedings of the National Academy of Sciences
USA, EMBO Journal, and Molecular Endocrinology, J. Clinical
Investigation, Oncogene, Virology, Genes and Development.
Publications:
- Privalsky, M. L. and E. E. Penhoet. 1977. Phosphorylated
protein component present in influenza virions. Journal of Virology.
24, 401-405.
- Privalsky, M. L. and E. E. Penhoet. 1978. Influenza virus
proteins: identity, synthesis, and modification analyzed by
two-dimensional gel electrophoresis. Proceedings of the National
Academy of Sciences USA. 75, 3625-3629.
- Privalsky, M. L. and E. E. Penhoet. 1981. The structure and
synthesis of influenza virus phosphoproteins. Journal of Biological
Chemistry 256, 5368-5376.
- Privalsky, M. L. and J. M. Bishop. 1982. Proteins specified
by avian erythroblastosis virus: coding region localization and
identification of a previously undetected erb B polypeptide. Proceedings
of the National Academy of Sciences USA, 79, 3958-3962.
- Bishop, J. M., T. Gonda, M. L. Privalsky, D. Sheiness, and
B. Vennstrom. 1982. Avian retrovirus genes that cause leukemia. In
Differentiation and Function of Hematopoietic Cell Surfaces.
Alan R. Liss, Inc. New York. pp. 263-271.
- Privalsky, M. L., L. Sealy, B. Vennstrom, and J., M. Bishop.
1983. The molecular genetics of avian erythroblastosis virus. In:
Gene expression in Normal and Transformed Cells. Edited by J. E.
Celis and R. Bravo. Plenum Press Inc, New York. pp. 193-208.
- Privalsky, M. L., L. Sealy, J. M. Bishop, J. P. McGrath, and
A. D. Levinson. 1983. The product of the avian erythroblastosis virus
erb B locus is a glycoprotein. Cell 32, 1257-1267.
- Sealy, L., G. Moscovici, C. Moscovici, M. L. Privalsky, and
J. M. Bishop. 1983. Site specific mutagenesis of avian erythroblastosis
virus: erb B is required for oncogenicity. Virology 130,
155-178.
- Privalsky, M. L., R. Ralston, and J. M. Bishop. 1984. The
membrane glycoprotein encoded by the retroviral oncogene v-erb B is
structurally related to tyrosine-specific protein kinases. Proceedings
of the National Academy of Sciences USA 81, 704-707.
- Privalsky, M. L. and J. M. Bishop. 1984. Subcellular
localization of the v-erb B protein, the product of a transforming gene
of avian erythroblastosis virus. Virology 135, 356-368.
- Schatzman, R. C., G. I. Evan, M. L. Privalsky, and J. M.
Bishop. 1986. Orientation of the v-erb B gene product in the plasma
membrane. Molecular and Cellular Biology 6, 1329-1333.
- Ng, M. and M. L. Privalsky. 1986. Structural domains of the
avian erythroblastosis virus erb B protein required for fibroblast
transformation: dissection by in-frame insertional mutagenesis. Journal
of Virology 58, 542-553.
- Bassiri, M. and M. L. Privalsky. 1986. Mutagenesis of the
avian erythroblastosis virus erb B coding region: an intact
extracellular domain is not required for oncogenic transformation. Journal
of Virology 59, 525-530.
- Privalsky, M. L. 1987. Creation of a chimeric oncogene:
analysis of the biochemical and biological properties of a v-erb B/src
fusion polypeptide. Journal of Virology 61, 1938-1948.
- Bassiri, M. and M. L. Privalsky. 1987. Transmembrane domain
of the avian erythroblastosis virus erb B oncogene protein is not
required for partial manifestation of the transformed phenotype. Virology
159, 20-30.
- Boucher, P., A. Koning, and M. L. Privalsky. 1988. The avian
erythroblastosis virus erb A oncogene encodes a DNA-binding protein
exhibiting distinct nuclear and cytoplasmic subcellular localizations.
Journal of Virology 62, 534-544.
- Privalsky, M. L., P. Boucher, A. Koning, and C. Judelson.
1988. Genetic dissection of functional domains within the avian
erythroblastosis virus v-erb A oncogene. Molecular and Cellular
Biology 8, 4510-4517.
- Privalsky, M. L. 1990. A subpopulation of the avian
erythroblastosis virus v-erb A protein, a member of the nuclear hormone
receptor family, is glycosylated. Journal of Virology 64,
463-466.
- Bonde, B. G. and M. L. Privalsky. 1990. Sequence-specific
DNA binding by the v-erb A protein. Journal of Virology 64,
1314-1320.
- Boucher, P. and M. L. Privalsky. 1990. Mapping of functional
domains within the v-erb A oncogene protein: the remnants of the hormone
binding domain play multiple vital roles in protein action. Oncogene
5, 1303-1311.
- Privalsky, M. L., M. Sharif, and K. R. Yamamoto. 1990. The
viral erb A oncogene protein, a constitutive repressor in animal cells,
is a hormone-regulated activator in yeast. Cell 63,
1277-1286.
- Privalsky, M. L. 1991 The v-erb A oncogene protein of avian
erythroblastosis virus exists in a high molecular weight complex with
heat shock protein-90. Journal of Biological Chemistry 266,
1456-1462.
- Bonde, B., M. Sharif, and M. L. Privalsky. 1991. Ontogeny of
the v-erb A oncoprotein from the thyroid hormone receptor: an alteration
in the DNA binding domain plays a role crucial for v-erb A function.
Journal of Virology 65, 2037-2056.
- Sharif, M. and M. L. Privalsky. 1991. V-erb A oncogene
function in neoplasia correlates with its ability to repress retinoic
acid receptor action. Cell 66, 885-893.
- Sharif, M. and M. L. Privalsky. 1992. V-erb A and c-erb A
proteins enhance transcriptional activation by c-jun. Oncogene
7, 953-960.
- Hall, B. L., B. G. Bonde, C. Judelson, and M. L. Privalsky.
1992. Functional interaction between the two zinc finger domains of the
v-erb A oncoprotein. Cell Growth and Differentiation. 3,
207-216.
- Privalsky, M. L. 1992. Retinoid and thyroid hormone
receptors: ligand-regulated transcription factors as protooncogenes. (An
invited review). Seminars in Cell Biology. 3, 99-106.
- Privalsky, M. L. 1992. V-erb A, nuclear hormone receptors,
and oncogenesis (An invited review). Biochimica et Biophysica Acta.
1114, 51-62.
- Smit-McBride, Z. and M. L. Privalsky. 1993. Functional
domains of the v-erb A protein required for transcriptional
activation in Saccharomyces cerevisiae. Oncogene 8,
1465-1475.
- Sande, S., M. Sharif, and M. L. Privalsky. 1993. V-erb
A effects on retinoic acid receptors in immature avian erythroid cells
suggest a mechanism of oncogene action. J. Virology 67,
1067-1074.
- Chen, H.-W., Z. S. McBride, S. Lewis, M. Sharif, and M. L.
Privalsky. 1993. Nuclear hormone receptors involved in neoplasia:
Erb A displays a novel DNA recognition specificity determined by
amino acids outside of the "zinc-finger" domain. Mol.
Cell. Biol. 13, 2366-2376 (1993).
- Chen, H.-W., and M. L. Privalsky. 1993. The erb A
oncogene inhibits both RAR and RXR classes of retinoid receptors, but by
different mechanisms. Mol. Cell. Biol. 13, 5970-5980.
- Hall, B., Z. Smit-McBride, and M. L. Privalsky. 1993.
Reconstitution of RXR function, and combinatorial regulation of other
nuclear hormone receptors, in the yeast Saccharomyces cerevisiae.
Proc. Nat. Acad. Sci. USA. 90, 6929-6933.
- Schuh, T., B. L. Hall, J. C. Kraft, M. L. Privalsky, and D.
Kimelman. 1993. V-erb A and citral reduce the teratogenic
effects of all-trans retinoic acid and retinol, respectively, in
Xenopus embryogenesis. Development 119, 785-798.
- Smit-McBride and M. L. Privalsky. 1994. DNA sequence
specificity of the v-Erb A oncoprotein/thyroid hormone receptor:
role of the P-box and its interaction with more N-terminal determinants
of DNA recognition. Molecular Endocrinology 8, 819-828.
- Sande, S. and M. L. Privalsky. 1994. Reconstitution of
retinoid and thyroid hormone receptor function in the fission yeast Schizosaccharomyces
pombe permits elucidation of novel receptor actions. Molecular
Endocrinology. 8, 1455-1462.
- Chen, H.W. and M. L. Privalsky. 1995. Cooperative formation
of high order oligomers by retinoid X receptors: an unanticipated mode
of DNA recognition. Proc. Natl. Acad. Sci. USA. 92,
422-426.
- Wong, C.-W. and M. L. Privalsky. 1995. Role of the
N-terminus in DNA recognition by the v-erb A protein, an
oncogenic derivative of a thyroid hormone receptor. Molecular
Endocrinology, 9, 551-562.
- Judelson, C. and M. L. Privalsky. 1996. DNA recognition by
normal and oncogenic thyroid hormone receptors. J. Biol. Chem. 271,
10800-10805.
- Sande, S. and M. L. Privalsky. 1996. Identification of
TRACs, a family of cofactors that associate with, and modify the
transcriptional properties of, nuclear hormone receptors. Molecular
Endocrinology 10, 813-825.
- Yoh, S., V. K. K. Chatterjee, and M. L. Privalsky.
1997. Thyroid hormone resistance syndrome manifests as an aberrant
interaction between mutant T3 receptors and transcriptional
corepressors. Molecular Endocrinology 11, 470-480.
- Lin, B. C., C.-W. Wong, H.-W. Chen, and M. L. Privalsky.
1997. Plasticity of tetramer formation by retinoid X receptors, an
alternative paradigm for DNA recognition. J. Biol. Chem. 272,
9860-9867.
- Chen, H.-W. and M. L. Privalsky. 1997. Retinoid X and
retinoic acid receptors interact with TFIIB by distinct mechanisms.
Mol. Cell. Endocrinology 129, 55-61.
- Hong, S.-H., G. David, C.-W. Wong, A. Dejean, and M. L.
Privalsky. 1997. SMRT corepressor interacts with PLZF, and with the
PML-RARa and PLZF-RARa oncoproteins associated with acute promyelocytic
leukemia. Proc. Natl. Acad. Sci. USA 94, 9028-9033.
- Lin, B. C., S.-H. Hong, S. Krig, S. M. Yoh, and M. L. Privalsky.
1997. A conformational switch in the nuclear hormone receptors is
involved in coupling hormone binding to corepressor release). Mol.
Cell. Biol. 17, 6131-6138.
- Chen, H.-W., R. J. Lin, D. Chakravarti, L. Schiltz, A. Nash, L.
Nagy, M. L. Privalsky, Y. Nakatani, and R. M. Evans. 1997.
Nuclear receptor co-activator ACTR is a novel histone acetyltransferase
and forms a multimeric activation complex with P/CAF and CBP/p300. Cell
90, 569-580.
- Tzagarakis, C. and M. L. Privalsky. Phosphorylation by
protein kinase A alters the DNA recognition properties of the thyroid
hormone receptor and the v-Erb A oncoprotein (Submitted to J Biol Chem).
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