Faculty

Michael Murphey-Corb, PhD Professor, Department of Microbiology and Molecular Genetics - School of Medicine and Department of Infectious Diseases and Microbiology - Graduate School of Public Health (Secondary Appointment) E-mail: mcorb@pitt.edu Phone: 412-648-9462 Address: E1252 Biomedical Science Tower 200 Lothrop Street Pittsburgh, PA 15261

Education

BS; Northeast Louisiana University; 1969
MT; Ochsner Foundation Hospital; 1969
MS; LSU Medical Center; 1977
PhD; LSU Medical Center; 1980

Research Interests

Characterization of protective immune responses to SIV; development of SIV vaccines with an emphasis on the mucosae; pathogenesis of SIV; SIV genetic evolution; development of nonhuman primate model for gene therapy.

Research Summary

Dr. Corb's research program consists of a multidisciplinary program utilizing the SIV: macaque model to study 1) the pathogenesis of SIV induced immunosuppression, 2) pathobiology of mucosal infection, 3) development of an efficacious vaccine against lentiviral infection and disease, and 4) application of the nonhuman primate model to identify effective therapeutic drugs. These tasks require expertise in virology, molecular biology, cell biology, immunology and primatology; procedures encompassing these fields are routinely performed in Dr. Corb's laboratory.

Dr. Corb has also held an avid interest in human genetics, and she is presently initiating studies to utilize the nonhuman primate as a model for gene therapy. A major focus of this program will be in utero therapy, beginning in early gestation with the immunologically incompetent fetus and ultimately expanding to germ line insertions in ex vivo fertilized eggs. An offshoot of this investigation that ties in with her funded research in vaccine development is the development of immunologically chimeric infants by inoculation of early gestation fetuses with CD34+ bone marrow progenitors from the father. These infants will be used in adoptive transfer studies to determine the role of cellular immunity in the protective responses induced by immunization of the father.

Recent Publications

• Seman, A. L., Pewen, W. F., Fresh, L. F., Martin, L. N., and Murphey-Corb, M.  (2000). The replicative capacity of rhesus macaque peripheral blood mononuclear cells for simian immunodeficiency virus in vitro is predictive of the rate of progression to AIDS in vivo. J. Gen. Virol., in press.
• Wilson, L. A., Murphey-Corb, M., Martin, L. N., Harrison, R., Ratteree, M., and Bohm, R. (2000). Identification of SIV env-specific CTL in the jejunal mocosa in vagionally-exposed, seronegative macaques. J. Med. Primatol., in press.
• Cole, K.S., Alvarez, M., Elliott, D.H., Lam, H., Martin, E., Chau, T., Micken, K., Rowles, J.L., Clements, J.E., Murphey-Corb, M., Montelaro, R.C, and Robinson, J.E.  (2001). Characterization of neutralization epitopes of simian immunodeficiency virus (SIV) recognized by rhesus monoclonal antibodies derived from monkeys infected with an attenuated SIV strain. Virology  290:59-73.
• Murphey-Corb, M. and Heydenburg-Fuller, D. (2001). Immunotherapy as an adjunct to highly-active antiretroviral therapy. Curr. Opin. Investig. Drugs 2:1191-1197.
• Fortgang, I.S., Rege, T., Baskin, G.B., Murphey-Corb, M., and Levy, L.S. (2001). Variation in simian immunodeficiency virus env V1 region in simian AIDS-associated lymphoma. AIDS Res. Hum. Retroviruses 17:459-465.
• Wolfe, D., Goins, W.F., Kaplan, T.J., Capuano, S.V., Fradette, J., Murphey-Corb, M., Robbins, P.D., Cohen, J.B., and Glorioso, J.C. (2001). Herpesvirus-mediated systemic delivery of nerve growth factor. Mol. Ther. 3:61-69.
• Sarkar, S., Kalia, V., Murphey-Corb, M., and Montelaro, R.C.   (2002). Characterization of CD4+ T helper cell fine specificity to the envelope glycoproteins of simian immunodeficiency virus. J. Med. Primatol. 31:194-204.
• Trichel, A.M., Rajakumar, P.A., and Murphey-Corb, M. (2002). Species-specific variation in SIV disease progression between Chinese and Indian subspecies of rhesus macaque. J. Med. Primatol. 31:171-178.
• Coates, P.T., Barratt-Boyes, S.M., Donnenberg, A.D., Morelli, A.E., Murphey-Corb, M., and Thomson, A.W.   (2002). Strategies for preclinical evaluation of dendritic cell subsets for promotion of transplant tolerance in the nonhuman primate. Hum. Immunol. 63:955-965.
• Fuller, C.L., Choi, Y.K., Fallert, B.A., Capuano, S. 3rd, Rajakumar, P., Murphey-Corb, M., and Reinhart, T.A.  (2002). Restricted SIV replication in rhesus macaque lung tissues during the acute phase of infection. Am. J. Pathol. 161:969-978.
• Stoltz, D.A., Nelson, S., Kolls, J.K., Zhang, P., Bohm, R.P., Murphey-Corb, M., and Bagby, G.J.   (2002). Effects of in vitro ethanol on tumor necrosis factor-alpha production by blood obtained from simian immunodeficiency virus-infected rhesus macaques. Alcohol Clin. Exp. Res. 26:527-534.
• Reinhart, T.A., Fallert, B.A., Pfeifer, M.E., Sanghavi, S., Capuano, S. 3rd, Rajakumar, P., Murphey-Corb, M., Day, R., Fuller, C.L., and Schaefer, T.M. (2002). Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome. Blood 99:3119-3128.
• Sarkar, S., Kalia, V., Murphey-Corb, M., and Montelaro, R.C.   (2002). Detailed analysis of CD4+ Th responses to envelope and Gag proteins of simian immunodeficiency virus reveals an exclusion of broadly reactive Th epitopes from the glycosylated regions of envelope. J. Immunol. 168:4001-4011.
• Zimmer, M.I., Larregina, A.T., Castillo, C.M., Capuano, S. 3rd, Falo, L.D. Jr, Murphey-Corb, M., Reinhart, T.A., and Barratt-Boyes, S.M.  (2002). Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS. Blood  99:2859-2868.
• Croix, D.A., Board, K., Capuano, S. 3rd, Murphey-Corb, M., Haidaris, C.G., Flynn, J.L., Reinhart, T., and Norris, K.A.   (2002). Alterations in T lymphocyte profiles of bronchoalveolar lavage fluid from SIV- and Pneumocystis carinii-coinfected rhesus macaques. AIDS Res. Hum. Retroviruses 18:391-401.
• Jordan-Sciutto, K.L., Wang, G., Murphey-Corb, M., and Wiley, C.A. (2002). Cell cycle proteins exhibit altered expression patterns in lentiviral-associated encephalitis. J. Neurosci.  22:2185-2195.
• Bissel, S.J., Wang, G., Ghosh, M., Reinhart, T.A., Capuano, S. 3rd, Stefano Cole, K., Murphey-Corb, M., Piatak, M. Jr, Lifson, J.D., and Wiley, C.A. (2002). Macrophages relate presynaptic and postsynaptic damage in simian immunodeficiency virus encephalitis. Am. J. Pathol. 160:927-941.
• Fuller, D.H., Rajakumar, P.A., Wilson, L.A., Trichel, A.M., Fuller, J.T., Shipley, T., Wu, M.S., Weis, K., Rinaldo, C.R., Haynes, J.R., and Murphey-Corb, M. (2002). Induction of mucosal protection against primary, heterologous simian immunodeficiency virus by a DNA vaccine. J. Virol. 76:3309-3317.
• Sarkar, S., Kalia, V., Murphey-Corb, M., Montelaro, R.C., and Reinhart, T.A. (2003). Expression of IFN-gamma induced CXCR3 agonist chemokines and compartmentalization of CXCR3+ cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome. J. Med. Primatol. 32:247-264.
• Safi, H., Gormus, B.J., Didier, P.J., Blanchard, J.L., Lakey, D.L., Martin, L.N., Murphey-Corb, M., Vankayalapati, R., and Barnes, P.F.   (2003). Spectrum of manifestations of Mycobacterium tuberculosis infection in primates infected with SIV. AIDS Res. Hum. Retroviruses. 19:585-595.
• Coates, P.T., Barratt-Boyes, S.M., Zhang, L., Donnenberg, V.S., O'Connell, P.J., Logar, A.J., Duncan, F.J., Murphey-Corb, M., Donnenberg, A.D., Morelli, A.E., Maliszewski, C.R., and Thomson, A.W. (2003). Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand. Blood 102:2513-2521.
• Ruff, K., Baskin, G.B., Simpson, L., Murphey-Corb, M., and Levy, L.S. (2003). Rhesus rhadinovirus infection in healthy and SIV-infected macaques at Tulane National Primate Research Center. J. Med. Primatol. 32:1-6.
• Bagby, G.J., Stoltz, D.A., Zhang, P., Kolls, J.K., Brown, J., Bohm, R.P. Jr., Rockar, R., Purcell, J., Murphey-Corb, M., and Nelson, S. (2003). The effect of chronic binge ethanol consumption on the primary stage of SIV infection in rhesus macaques. Alcohol Clin.  Exp. Res. 27:495-502.
• Board, K.F., Patil, S., Lebedeva, I., Capuano, S. 3rd, Trichel, A.M., Murphey-Corb, M., Rajakumar, P.A., Flynn, J.L., Haidaris, C.G., and Norris, K.A. (2003). Experimental Pneumocystis carinii pneumonia in simian immunodeficiency virus-infected rhesus macaques. J. Infect. Dis. 187:576-588.
• Choi, Y.K., Fallert, B.A., Murphey-Corb, M.A., and Reinhart, T.A.  (2003). Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo. Blood 101:1684-1691.
• Choi, Y.K., Whelton, K.M., Mlechick, B., Murphey-Corb, M.A., and Reinhart, T.A. (2003) Productive infection of dendritic cells by simian immunodeficiency virus in macaque intestinal tissues. J. Pathol. 201:616-628.
• Brown, K., Gao, W., Alber, S., Trichel, A., Murphey-Corb, M., Watkins, S.C., Gambotto, A., and Barratt-Boyes, S.M. (2003) Adenovirus-transduced dendritic cells injected into skin or lymph node prime potent simian immunodeficiency virus-specific T cell immunity in monkeys. J. Immunol. 171:6875-6882.
• Venneti, S., Lopresti, B.J., Wang, G., Bissel, S.J., Mathis, C.A., Meltzer, C.C., Boada, F., Capuano, S. 3rd, Kress, G.J., Davis, D.K., Ruszkiewicz, J., Reynolds, I.J., Murphey-Corb, M., Trichel, A.M., Wisniewski, S.R., and Wiley, C.A. (2004) PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS. J. Clin. Invest. 113:981-989.
• Medina-Flores, R., Wang, G., Bissel, S.J., Murphey-Corb, M., and Wiley, C.A. (2004) Destruction of extracellular matrix proteoglycans is pervasive in simian retroviral neuroinfection. Neurobiol. Dis. 16:604-616.

• Wolfe, D., Niranjan, A., Trichel, A., Wiley, C., Ozuer, A., Kanal, E., Kondziolka, D., Krisky, D., Goss, J., Deluca, N., Murphey-Corb, M., and Glorioso, J.C. (2004)  Safety and biodistribution studies of an HSV multigene vector following intracranial delivery to non-human primates.  Gene Ther.  11:1675-1684.

• Nti, B.K., Slingluff, J.L., Keller, C.C., Hittner, J.B., Ong'echa, J.M., Murphey-Corb, M., and Perkins, D.J. (2005).  Stage-specific effects of Plasmodium falciparum-derived hemozoin on blood mononuclear cell TNF-alpha regulation and viral replication.  AIDS 19:1771-1780.