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Thomas Jefferson University - D. Craig Hooper, PhD
D. Craig Hooper, PhD

Cancer Biology
Thomas Jefferson University
Jefferson Medical College
Department of Cancer Biology
Department of Neurological Surgery
Professor
Appointed: 2012
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Mailing Address

Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: (215) 503-1774
Douglas.Hooper@jefferson.edu
Expertise and Research Interests
Research Interests

The principle research area of the Hooper laboratory is CNS immunity and, particularly, the balance between protective and destructive neuroinflammatory processes. CNS tissues are protected from immune mechanisms by the blood-brain barrier (BBB) and a major focus of the lab is on mechanisms that modulate BBB integrity and how these impact protective versus pathological CNS inflammatory and neurodegenerative conditions. Important questions are how does the therapeutic delivery of immune effectors across the BBB during virus clearance differ from pathological immune cell invasion into the CNS parenchyma and how are these processes regulated? We were the first to show that peroxynitrite-dependent radicals open the BBB during a CNS inflammatory response and that the sources of these radicals differ between pathological and therapeutic immune cell invasion into CNS tissues. Our current projects are directed at understanding the mechanisms through which therapeutic immune cells and molecules, such as lymphocytes and antibodies, are naturally delivered to CNS tissues during a CNS immune response such that these processes may be manipulated therapeutically for the treatment of neurotropic virus infection, neurodegenerative disease, and brain cancer. For example, we have discovered that the protective alterations in BBB function required for immune effector infiltration into CNS tissues during the therapeutic clearance of attenuated rabies viruses are inhibited during infection with highly pathogenic rabies viruses. This enables pathogenic rabies viruses to evade immune clearance and cause a lethal infection despite eliciting strong anti-viral immune responses in the periphery. We are assessing various strategies to circumvent this block and deliver therapeutic reagents into the infected CNS tissues, approaches that will also be used to target immune effectors to CNS tumors. From the opposite perspective we are continuing our long-term studies of peroxynitrite-dependent radical inactivation as a means to maintain BBB integrity and prevent potentially pathological cells and factors from infiltrating into CNS tissues. We pioneered the approach of raising serum levels of urate, a natural peroxynitrite-dependent radical scavenger, for the treatment of CNS autoimmunity, a strategy that is the foundation of several clinical trials in multiple sclerosis (MS) and Parkinsons disease. Current studies are directed at understanding the pathways through which the peroxynitrite-dependent radicals inactivated by urate mediate their effects on the BBB and CNS tissues.
Keywords
Immunology; Microbiology; Neuroimmunology; Virology; Immunology; Virology; Neuroimmunology; Inflammation; Free Radicals; Glioma; Cancer Vaccines
Publications
  • Castegna, A., Palmieri, L., Spera, I., Porcelli, V., Palmieri, F., Fabis-Pedrini, M.J., Kean, R.B., Barkhouse, D.A., Curtis, M.T., and Hooper, D.C. Oxidative stress and reduced glutamine synthetase activity in the absence of inflammation in the cortex of mice with experimental allergic encephalomyelitis. Neuroscience 185:97-106, 2011.
  • Hooper, D.C., Roy, A., Kean, R.B., Phares, T.W., and Barkhouse, D. A. Therapeutic immune clearance of rabies virus from the CNS. Future Virology, 6: 387-397, 2011.
  • Hooper D.C., Phares, T.W., Fabis, M.J., and Roy, A. The production of antibody by invading B cells is required for the clearance of rabies virus from the central nervous system. PLoS Negl. Trop. Dis. 3(10) e535, 2009.
  • Faber, M., Li, J., Kean, R.B., Hooper, D.C., Alugupalli, K.R., and Dietzschold, B. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus. Proc Natl Acad Sci USA., Jul 7: 106(27): 11300-5, 2009.
  • Fabis, M.J., Phares, T.W., Kean, R.B., Koprowski, H., and Hooper, D.C. Blood-brain barrier changes and cell invasion differ between therapeutic immune clearance of neurotrophic virus and CNS autoimmunity. Proc Natl Acad Sci USA., Oct 7;105(40):15511-6, 2008.
  • Roy, A. and Hooper, D.C. Lethal Silver-Haired Bat Rabies Virus Infection Can Be Prevented by Opening the Blood-Brain Barrier. J Virol. 2007 81:7993-7998.
  • Phares, T.W., Fabis, M.J., Brimer, C.M., Kean, R.B., and Hooper, D.C. A peroxynitrite-dependent pathway is responsible for blood-brain barrier permeability changes during a central nervous system inflammatory response: TNF-alpha Is neither necessary nor sufficient. J Immunol. 2007 178(11):7334-43.
  • Fabis M.J., Scott G.S., Kean R.B., Koprowski H., Hooper D.C. Loss of blood-brain barrier integrity in the spinal cord is common to experimental allergic encephalomyelitis in knockout mouse models. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5656-61.
  • Roy, A., Phares, T.W., Koprowski, H., and Hooper, D.C. Failure to open the blood-brain barrier and deliver immune effectors to the CNS tissues leads to the lethal outcome of Silver-haired bat rabies virus infection. J Virol. 2007 Feb;81(3):1110-8.
  • Phares T.W., Kean R.B., Mikheeva T., and Hooper D.C. Regional differences in blood-brain barrier permeability changes and inflammation in the apathogenic clearance of virus from the central nervous system. J Immunol. 176: 7666-75 2006.
  • Hooper, D.C. The role of immune responses in the pathogenesis of rabies. J Neurovirol., 11: 88-92, 2005.
  • Scott, G.S., Cuzzocrea, S., Genovese, T., Koprowski, H., and Hooper, D.C. Uric acid protects against secondary damage after spinal cord injury. Proc Natl Acad Sci U S A. 102: 3483-8, 2005.
  • Scott, G.S., Kean, R.B., Fabis, M.J., Mikheeva, T., Brimer, C.M., Phares, T.W., Spitsin, S.V., and Hooper, D.C. ICAM-1 upregulation in the spinal cords of PLSJL mice with experimental allergic encephalomyelitis is dependent upon TNF-alpha production triggered by the loss of blood-brain barrier integrity. J Neuroimmunol. 155: 32-42, 2004.
  • Kanabrocki, E.L., Ryan, M.D., Hermida, R.C., Ayala, D.E., Scott, G.S., Murray, D., Bremner, W.F., Third, J.L.H.C., Johnson, M.C., Foley, S., Van Cauteren, J., Shah, F., Shirazi, P., Nemchausky, B.A., and Hooper, D.C. Altered circadian relationship between serum nitric oxide, carbon dioxide, and uric acid in multiple sclerosis. Chronobiology Int. 21: 739-758, 2004.
  • Scott, G.S., Virag, L., Szab√≥, C. and Hooper, D.C. Peroxynitrite-induced oligodendrocyte toxicity is not dependent on poly(ADP-ribose) polymerase activation. GLIA, 41: 105-116, 2003.
  • Prosniak, M., Zborek, A., Scott, G.S., Roy, A., Phares, T.W., Koprowski, H., and Hooper, D.C. Differential expression of growth factors at the cellular level in virus-infected brain. Proc Natl Acad Sci U S A. 100: 6765-70, 2003.
  • Scott, G.S., Spitsin, S.V., Kean, R.B., Mikheeva, T., Koprowski, H., and Hooper, D.C. Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. Proc Natl Acad Sci USA 99: 16303-16308, 2002.
  • Kanabrocki, E.L., Murray, D., Hermida, R.C., Scott, G.S., Bremner, W.F., Ryan, M.D., Ayala, D.E., Third, J.L., Shirazi, P., Nemchausky, B.A., and Hooper, D,C. Circadian variation in oxidative stress markers in healthy and type II diabetic men. Chronobiol Int. 19: 423-39, 2002.
  • Koprowski, H., Spitsin, S.V. and Hooper, D.C. Prospects for the treatment of multiple sclerosis by raising serum levels of uric acid, a scavenger of peroxynitrite. Annals of Neurology. 49: 139, 2001.
  • Scott, G.S. and Hooper D.C. The Role of uric acid in protecting the central nervous system from peroxynitrite-mediated pathology. Medical Hypotheses. 56: 95-100, 2001.
  • Hooper DC, Scott GS, Zborek A, Mikheeva T, Kean RB, Koprowski H, Spitsin SV. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. Faseb Journal. 14: 691-8, 2000.
  • Kean, R.B. Spitsin, S.V., Mikheeva, T., Scott, G.S. and Hooper, D.C. The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the CNS in experimental allergic encephalomyelitis through maintenance of blood-CNS barrier integrity. J Immunology. 165: 6511-6518, 2000.
  • Hooper DC, Morimoto K, Bette M, Weihe E, Koprowski H, Dietzschold B. Collaboration of antibody and inflammation in clearance of rabies virus from the central nervous system. J Virology. 72: 3711-9, 1998.
  • Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, Chaudhry I, Koprowski H. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Nat Acad Sci USA. 95: 675-80,1998.

Individual Expertise profile of D. Craig Hooper, PhD, Copyright © D. Craig Hooper, PhD.
Last Updated by D. Hooper, PhD : Friday, April 6, 2012 1:33:41 PM



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