Harry T. Orr, Ph.D.

Professor
612-625-3647
orrxx002@umn.edu

Educational Background

• Oakland University, Rochester, MI (1971), B.A. (Biology)
• Washington University, St. Louis, MO (1976), Ph.D. (Neurobiology)
• Harvard University, Cambridge, MA (1980), Research Fellowship (Biochemistry and Molecular Biology)

Professional Background

• Assistant Professor , University of Minnesota Medical School, Department of Laboratory Medicine and Pathology, 1980 - 1984
• Associate Professor , University of Minnesota Medical School, Department Laboratory Medicine and Pathology, 1984 - 1989
• Professor of Pathology, University of Minnesota Medical School, Department of Laboratory Medicine and Pathology, 1989 - present
• Member, University of Minnesota, Institute of Human Genetics, 1984 - present
• Professor, University of Minnesota, Biochemistry, 1994 - present
• Director, University of Minnesota, Institute of Human Genetics, 1998 - present

Professional Honors

• Leukemia Society of America Special Fellow, 1979 - 1981
• Searle Scholar Award, 1981 - 1984
• Leukemia Society of America Scholar, 1982 - 1987
• Young Investigator Award, American Soc. of Histocompatibility Immunogenetics, 1985
• Kilby International Award, 1995
• MERIT Award, NIH/NIAID, 1995 - 2000
• Milton Wexler Award for Research in HD, HDSA, 1999
• Javits Investigator Award, NINDS/NIH, 2004

Professional Memberships

• NIH, NIAID, Transplantation & Immunogenetics Subcommittee, 1984 - 1988
• NIH, DRG Member Mammalian Genetics Study Section , 1989 - 1993
• NIH, NIAID, Ad-hoc Council Member, 1992 - 1992
• NIH, DRG Member Mammalian Genetics Study Section, 1997 - 2000
• NIH, DRG, Chair Mammalian Genetics Study Section, 1998 - 2000

Community and University Service

• Developmental Biology Symposium, 1994
• Center of Developmental Biology Executive Committee, 1994
• Organizing Committee Developmental Biology Symposium, 1994
• Graduate School Health Sciences Research Advisory Committee, 1994
• University Senate

Research Interests

Dr. Orr's research program is focused on the molecular genetics of mammalian development and neurodegenerative diseases. He and his colleagues recently cloned the gene for an autosomal dominant form of spinocerebellar ataxia (SCA 1). They showed that the disease is due to expansion of an unstable trinucleotide repeat (CAG) within the SCA 1 gene, which they have mapped to the short arm of human chromosome. They are examining the role of the SCA 1 gene in normal CNS function and how this mutation disrupts this function. The investigators will be working with protein biochemists to characterize the normal and abnormal SCA 1 protein.

Publications

• Orr, H.T., Chung, M.-y., Banfi, S., Kwiatkowski, T.J., Servadio, A., Beaudet, A.L., McCall, A.E., Duvick, L.A., Ranum, L.P.W., and Zoghbi, H.Y. (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genet., 4:221-226.
• Chung, M.-y., Ranum, L.P.W., Duvick, L.A., Servadio, A., Zoghbi, H.Y., and Orr, H.T. (1993) Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nature Genet., 5:254-258.
• Feddersen, R.M., Clark, H.B., Yunis, W.S., and Orr, H.T. (1995) In vivo viability of postmitotis Purkinje neurons requires pRb family member and function. Mol. Cell. Neurosci. 6: 153-167.
• Burright, E.N., Clark, H.B., Servadio, A., Matilla, T., Feddersen, R.M., Yunis, W.S., Duvick, L.A., Zoghbi, H.Y., and Orr, H.T. (1995) SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell, 82:937-948.
• Banfi, S., Servadio, A., Chung, M.-y., Capozzoli, F., Duvick, L.A., Elde, R., Zoghbi, H.Y., and Orr, H.T. (1996) Cloning and developmental expression analysis of the murine homolog of the spinocerebellar ataxia type 1 gene (Sca1). Hum. Mol. Genet. 5: 33-40.
• Kaytor, M.D., Burright, E.N., Duvick, L.A., Zoghbi, H.Y., and Orr, H.T. (1997) Increased CAG repeat instability with advanced maternal age in SCA1 transgenic mice. Hum. Mol. Genet. 6: 2135-2139.
• Skinner, P.J., Koshy, B., Klement, I.A., Helin, K., Servadio, A., Zoghbi, H.Y., and Orr, H.T. (1997) SCA1 pathogenesis involves alterations in nuclear matrix-associated structures. Nature 389: 971-974.
• Klement, I.A., Skinner, P.J., Kaytor, M.D., Yi, H., Hersch, S.M., Clark, H.B., Zoghbi, H.Y., and Orr, H.T. (1998) Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95:41-53.
• Davidson, J.D., Riley, B., Burright, E.N., Duvick, L. A., Zoghbi, H.Y., and Orr, H.T. (2000) Identification and characterization of an ataxin-1 interacting protein: A1Up a ubiquitin-like nuclear protein. Hum. Mol. Genet. 9: 2305-2312.
• Yue, S., Serra, H., Zoghbi, H.Y., and Orr, H.T. (2001) The SCA1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract. Hum. Mol. Genet. 10: 25-30.
• Skinner, P.J., Vierra-Green, C.A., Clark, H.B., Zoghbi, H.Y., and Orr, H.T. (2001) Altered Purkinje Cell Membrane Protein Trafficking in SCA1 Transgenic Mice. Amer. J. Path. 159: 905-913.
• Emamian, E.S. , Kaytor, M.D., Duvick, L.A., Zu, T., Tousey, S.K., Zoghbi, H.Y., Clark, H.B., and Orr, H.T. (2003) Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron 38: 975-987.
• Chen, H.-K, Fernandez-Funez, P., Acevedo, S.F., Lam, Y.C., Kaytor, M.D., Fernandez, M.H., Aitken, A., Skoulakis, E.M.C., Orr, H.T., Botas, J., and Zoghbi, H.Y. (2003) Interaction of Akt-Phosphorylated Ataxin-1 with 14-3-3 Mediates Neurodegeneration in Spinocerebellar Ataxia type 1. Cell 113: 457-468.
• Xia, H., Mao, Q., Eliason, S.I., Harper, S.Q., Martins, I.H., Orr, H.T., Paulson, H.L., Yang, L., Kotin, R.M., and Davidson, B.I. (2004) RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Medicine 10: 816-820.
• Riley, B.E., Xu, Y., Zoghbi, H.Y., and Orr, H.T. (2004) The polyglutamine repeat protein ataxin-1 and its effects on the UbL-UBA protein, A1Up. J. Biol. Chem., 279: 42290-42301
• Serra, H.G., Byam, C.E., Lande, J.D., Tousey, S.K., Zoghbi, H.Y., and Orr, H.T. (2004) Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice. Hum. Mol. Genet. 13: 2535-2543.
• Zu, T., Duvick, L.A., Kaytor, M.D., Berlinger, M., Zoghbi, H.Y., Clark, H.B., and Orr, H.T. (2004) Recovery from polyglutamine-induced neurodegeneration in conditional SCA1 transgenic mice. J. Neurosci. 24: 8853-8861.
• Kaytor, M.D., Byam, C.E., Tousey, S.K., Stevens, S.D., Zoghbi, H.Y., and Orr, H.T. (2005) A cell-based screen for modulators of ataxin-1 phosphorylation. Hum. Mol. Genet.14: 1095-1105.
• Riley, B.E., Zoghbi, H.Y., and Orr, H.T. (2005) SUMOylation of the polyglutamine protein, ataxin-1 is dependent ona functional nuclear localization signal. J. Biol. Chem. 280: 21942-21948.