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Department of Pharmacology
Randall N. Pittman, Ph.D.

Education:

1972	B.S. (Chemistry)	University of North Carolina
1981	Ph.D. (Pharmacology)	University of Colorado
1983	Postdoctoral Research	Harvard University
1985	Postdoctoral Research	California Institute of Technology

Research Summary:
Cellular and molecular approaches are used to study the normal and pathological functions of the polyglutamine neurodegenerative disease protein, ataxin-3, and signaling pathways controlling the execution stage of apoptosis. Apoptosis experiments focus on understanding regulation of execution events by Rho kinase signaling pathways with particular emphasis on dynamic membrane blebbing, cell fragmentation, and cellular processes that prepare cells for phagocytosis. Studies on the polyglutamine disease protein, ataxin-3, focus on understanding its normal cellular functions as a deubiquitylating enzyme and how this may be related to its pathology in spinocerebellar ataxia type 3/ Machado-Joseph disease. Ongoing projects are investigating the role of ataxin-3 in the ubiquitin proteasome pathway, interaction with DNA repair proteins, and neuronal transport mechanisms. Ataxin-3 is the first member of a new family of deubiquitylating enzymes and we are currently characterizing cellular and biochemical properties of other members of this new family of enzymes.

Selected Key Publications:
Mills JC, Stone NL, Erhardt J & Pittman RN: Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation. J Cell Biology 140: 627-636, 1998.

Warrick JM, Paulson HL, Gray-Board GL, Bui QT, Fischbeck KH, Pittman RN & Bonini NM: Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell 93: 939-949, 1998.

Perez MK, Paulson HL, Pendse SJ, Saionz SJ, Bonini NM & Pittman RN: Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J Cell Biol 143: 1457-1470, 1998.

Mills JC, Stone NL & Pittman RN: Extranuclear apoptosis: The role of the cytoplasm in the execution phase. J Cell Biol 146: 703-708, 1999.

Li, F., Macfarlan, T., Pittman, R.N. and Chakravarti, D. Ataxin-3 is a histone binding protein with two independent transcriptional corepressor activities. J. Biol. Chem., 277:45004-45012, 2002.

Zhou H, Li X-M, Meinkoth J & Pittman RN: Akt regulates cell survival and apoptosis at a post-mitochondrial level. J Cell Biol 151: 483-494, 2000.

Burnett B, Li F & Pittman RN: The polyglutamine neurodegenerative protein ataxin-3 binds polyubiquitylated proteins and has ubiquitin protease activity. Hum Mol Genet 12 :3195-3205, 2003.

Burnett BG & Pittman RN: The polyglutamine neurodegenerative protein ataxin 3 regulates aggresome formation. Proc Natl Acad Sci USA 102: 4330-4335, 2005.

Orlando, K.A., and Pittman, R.N. Rho kinase regulates phagocytosis, surface expression of GlcNAc, and Golgi fragmentation of apoptotic PC12 cells. Exp. Cell Res. 312:3298-3311, 2006.

Bilen, J., Liu, N., Burnett, B.G., Pittman, R.N. and Bonini, N.M. MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Mol. Cell 24:157-163, 2006.

Zhong, X. and Pittman, R.N. Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates. Hum. Mol. Genet. 15:2409-2420, 2006.