Pamela J. Skinner
331 Veterinary Science
1971 Commonwealth Avenue
University of Minnesota
St. Paul, MN55108
B.S., Genetics and Cell Biology, Univ. of Minnesota
Ph.D., Pathobiology, Univ. of Minnesota
Research in my laboratory focuses on two distinct research programs. The goals of the first program are to gain insights into prion disease pathogenesis, to develop novel assays to diagnosis prion diseases prior to the onset of clinical symptoms, and to develop an effective treatment for prion diseases. Prion diseases are fatal neurodegenerative diseases with no known cure. Increased understanding of the molecular events that lead to neurodegeneration in these diseases is needed for early diagnosis and the development of new drug therapies. We have identified hundreds of alterations in gene and protein expression that occur during the early stages of prion disease. Early changes in gene/protein expression may be important molecular events underlying prion disease pathogenesis, and these disease induced changes may serve as surrogate markers of disease and be useful for disease diagnosis as well as targets for drug therapy. The goals of the second research program are to gain insights into human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) pathogenesis and to help develop an effective HIV vaccine and novel therapies to treat HIV. The HIV/SIV program is motivated by the fact that over 40 million people worldwide are infected with HIV. A pressing biomedical priority is the development of an effective HIV vaccine. Several lines of evidence have indicated that the development of an effective HIV vaccine will require the induction of a strong localized virus specific cytotoxic T lymphocyte (CTL) response. We are using MHC-class I tetramers to stain and evaluate the localization, abundance, and phenotype of SIV and HIV specific CTLs in tissues to identify correlates of successful vaccination and to identify and characterize reservoirs where HIV/SIV accumulate and virus-specific CTL are excluded.
(For a comprehensive list of Dr. Skinner's recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Location and Dynamics of the Immunodominant CD8 T Cell Response to SIVΔnef Immunization and SIVmac251 Vaginal Challenge. Sasikala-Appukuttan AK, Kim HO, Kinzel NJ, Hong JJ, Smith AJ, Wagstaff R, Reilly C, Piatak M Jr, Lifson JD, Reeves RK, Johnson RP, Haase AT, Skinner PJ. PLoS One. 2013 Dec 9;8(12):e81623. doi: 10.1371/journal.pone.0081623.
Ping Wang, Kristen Hatcher, Jason Bartz, Shu G Chen, Pamela J Skinner, Juergen A. Richt, Hong Liu, and Srinand Sreevatsan, Selection and Characterization of Aptamers against PrPSc, Exp Biol Med. 2011; 236:466-476
Qingsheng Li, Pamela J. Skinner, Lijie Duan., A Technique to Simultaneously Visualize Virus-Specific CD8+ T Cells and Virus-Infected Cells in situ, published in both Science and Journal of Visualized Experimentation, 2009.
Jung Joo Hong, Teresa L. Mattila, Aaron Hage, Matthew R. Reynolds, David I. Watkins, Christopher J. Miller, and Pamela J. Skinner, Localized Populations of CD8- SIV-Specific T Cells in Lymphoid Follicles and Vaginal Epithelium of SIV infected macaques. PloS ONE, 2009; 4(1): e4131.
Qingsheng Li, Pamela J. Skinner, Sang-Jun Ha, Lijie Duan, Teresa L. Mattila, Aaron Hage, Cara White, Daniel L. Barber, Leigh O’Mara, Peter J. Southern, Cavan S. Reilly, Christopher J. Miller, Rafi Ahmed., Visualizing antigen specific and infected cells in situ predicts outcome in early viral infection. Science, 2009; 323(5922):1726-1729.
Hyeon O. Kim, Greg Snyder, Tyler M. Blazey, Bruce Chesebro, Richard E. Race, and Pamela J. Skinner, Prion disease induced alterations in gene expression in the spleen and brain prior to clinical symptoms. Computational Biology and Chemistry, 2008; 1:29-50.
Meritxell Genescà, Pamela. J. Skinner, Jung Joo Hong, Jun Li, Ding Lu, Michael B. McChesney, Christopher J. Miller, CD8+ T cells mediate protection of monkeys immunized with attenuated SHIV89.6 with minimal systemic T cell expansion. Journal of Virology, 2008. Nov; 82(22):11181-96.
Meritxell Genescà, Pamela J. Skinner, Kristen M. Bost, Ding Lu, Yichuan Wang, Tracy L. Rourke, Ashley T Haase, Michael B. McChesney, Christopher J. Miller. Protective attenuated lentivirus immunization induces polyfunctional SIV-specific T cells in the vagina and lymphoid tissues of rhesus macaques, Nature-Mucosal Immunology, 2008; 1(3): 219-228.
Justin M. Greene, Benjamin J. Burwitz, Alex J. Blasky, Teresa L. Mattila, Jung Joo Hong, Eva G. Rakasz, Roger W. Wiseman, Kim J. Hasenkrug, Pamela J. Skinner, Shelby L. O'Connor, David H. O'Connor, Allogeneic Lymphocytes Persist and Traffic in Feral MHC-Matched Mauritian Cynomolgus Macaques, PLoS-ONE, 2008; 3(6): e2384.
Elizabeth Connick, Terri Mattila, Joy M. Folkvord, Rick Schlichtemeier, Amie L. Meditz, Aaron Hage, Cara White, and Pamela J. Skinner. HIV-1-Specific CD8+ Cells Fail to Accumulate in Lymphoid Follicles Where Virus Replication is Concentrated, Journal of Immunology, 2007; 178(11): 6975-6983.
Pamela J. Skinner, Hayet Abbassi, Bruce Chesebro, Richard Race, Cavan Reilly, and Ashley T. Haase. Gene expression alterations in brains of mice infected with three strains of scrapie. BMC Genomics; 7(114), 2006.
Matthew R. Reynolds, Eva Rakasz, Pamela J. Skinner, Cara White, Kristina Abel, Min Ma, Lara Compton, Gnankang Napoé, Nancy Wilson, Christopher J. Miller, Ashley Haase, David I. Watkins. The CD8+ T-Lymphocyte Response to Major Immunodominant Epitopes after Vaginal Exposure to SIV: Too Late and Too Little. Journal of Virology, 2005 Jul;79(14):9228-35
Skinner, P.J., Haase, A.T. 2002. In situ tetramer staining. Journal of Immunological Methods. 268: 29–34.
Skinner, P.J., Vierra-Green, C.A., Emamian, E., Zoghbi, H.Y., Orr, H.T. 2002. Amino acids in a region of ataxin-1 outside of the polyglutamine tract influence the course of disease in SCA1 transgenic mice. Neuromolecular Medicine. 1(1):33–42.
Mothé, B.R., Horton, H., Carter, D.K., Liebl, M.E., Skinner, P.J., Allen, T.M., Vogel, T.U., Franchini, G., Rehrauer, W., Wilson, N., Altman, J.D., Haase, A.T., Picker, L.J., Sette, A.D., Watkins, D.I. 2002. Dominance of CD8 Responses Specific for Epitopes Bound by a Single MHC Class I Molecule During Both the Acute and Chronic Phases of Viral Infection. Journal of Virology. 76(2): 875–84.
Skinner, P.J., Vierra-Green, C.A., Clark, H.B., Zoghbi, H.Y., Orr, H.T. 2001. Altered trafficking of membrane proteins in Purkinje cells of SCA1 transgenic mice. American Journal of Pathology. 159, 905–13.
Skinner, P.J., Daniels, M.A., Schmidt, C.S., Jameson, S.C., Haase, A.T. 2000. In situ tetramer staining of antigen-specific T cells in tissues. Journal of Immunology 165 (2): 613–617.
Kaytor, M.D., Duvick, L.A., Skinner, P.J., Koob, M.D., Ranum, L.P.W., Orr, H.T. 1999. Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7. Human Molecular Genetics 8(9): 1657–1664.
Klement, I.A., Skinner, P.J., Kaytor, M.D., Hong, Y., Hersch, S.M., Clark, H.B., Zoghbi, H.Y., Orr, H.T. 1998. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95: 41–53.
Skinner, P.J., Koshy, B.T., Cummings, C.J., Klement, I.A., Helin, K., Servadio, A., Zoghbi, H.Y., Orr, H.T. 1997. Ataxin-1 With an Expanded Glutamine Tract Alters Nuclear Matrix-Associated Structures. Nature 389: 971–974.
NIH R01 AI080418, CTL Exclusion from Lymphoid Follicles as a Mechanism of Lentivirus Immune Evasion, Role: Principal Investigator, 20% effort, 6/15/10-5/31/11, $750,436.
NIH, Direct visualization of HIV-specific T cells during chronic HIV infection, Role: Prinipal Investigator, 6% effort, 2010-2011, $125,413.
Wisconsin National Primate Research Center, SIV-specific CD4 T cell analysis during acute SIV infection using MHC class II tetramers. Role: Principal Investigator, 10% effort, 2009-2011, $150,000.
NIH, Impact of very large numbers of SIV-specific CD8 T cells on vaginal transmission, Role: Co-Investigator, 12% effort, 2010-2014, $3,188,975.