Dr. William Klimstra is an associate professor in the Microbiology and Molecular Genetics Department and a member of the CVR, having relocated recently to the University of Pittsburgh from Louisiana State University Health Sciences Center. He received his undergraduate degree in Microbiology from Southern Illinois University in 1991 after spending several years also working as a field researcher studying wetland habitat development as an alternative reclamation technique for areas disturbed by surface coal mining in the midwestern United States. He received his Ph.D. from the Department of Microbiology and Immunology at the University of North Carolina at Chapel Hill in 1998 and also completed post-doctoral studies there in the laboratory of Dr. Robert Johnston where he first began work with arthropod-borne positive sense RNA viruses (arboviruses). Some of these viruses required biosafety level 3 containment and/or were Select Agent viruses, reflecting their potential for use as agents of bioterrorism/biowarfare. Through his post-doctoral studies, he became interested in the interaction of arboviruses with sentinel cells of the immune system such as macrophages and dendritic cells, recognizing that this early virus-cell interaction often determines the extent and magnitude of virus replication within the infected vertebrate host as well as the severity of viral disease. In 2000, he was promoted to an assistant professor for research at UNC and in 2002 chose to accept a tenure-track assistant professor position at LSUHSC. His laboratory currently investigates the nature of host cell structures serving as attachment and entry receptors on immune system sentinel cells as well as the nature and effectiveness of the innate immune interferon responses of the cells versus different arboviruses, in particular alphaviruses and flaviviruses. He is interested in understanding the mechanisms through which antiviral effectors of the innate immune system act and using this information for the development of new generations of antiviral drugs. More recently, he has also begun applying the results of these studies to improvement of vaccine and gene therapy vectors derived from arboviruses
- Christina Gardner, Jozef Hritz, Christopher Weiss, Dana Vahalaningam, Stephen Higgs, Elodie Ghedin, William Klimstra and Kate Ryman. 2014. Deliberate Attenuation of Chikungunya Virus by Adaptation to Heparan Sulfate-Dependent Infectivity: A Model for Rational Arboviral Vaccine Design. Accepted by PLOS Neglected Tropical Diseases 01/15/14.
- Hyde JL, Gardner CL, Kimura T, White JP, Liu G, Trobaugh DW, Huang C, Tonelli M, Paessler S, Takeda K, Klimstra WB, Amarasinghe GK, Diamond MS. 2014. A viral structural element alters host recognition of nonself RNA. Science 343:783-7.
- Trobaugh, D.W., C.L. Gardner, E. Wang, A. Haddow, S.C. Weaver, K.D. Ryman and W.B. Klimstra. 2014. RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature 506:245-8.
- Chengqun Sun, Christina L. Gardner, Alan D. Watson, Kate D. Ryman and William B. Klimstra. 2014. Stable, high-level expression of reporter proteins from improved alphavirus expression vectors to track replication and dissemination during encephalitic and arthritogenic disease. J. Virol. 88:2035-46.
- Michael Conway, Alan Watson, Tonya Colpitts, Srdjan Dragovic, Zhiyong Li, Penghua Wang, Fabiana Feitosa, Denueve Shepherd, Kate Ryman, William Klimstra, John Anderson, and Erol Fikrig. 2013. Mosquito saliva serine protease enhances dissemination of dengue virus into the mammalian host. J. Virol. 88:165-75.
- Gardner, C.L. J. Nurvatidhi, C. Sun, A. Bayer, J. Hritz, K.D. Ryman and W.B. Klimstra. 2013. Natural variation in the heparan sulfate binding domain of the eastern equine encephalitis virus E2 glycoprotein alters interactions with cell surfaces and virulence in mice. J. Virol. 87:8582-90.
- Gardner, C.L., G.D. Ebel, K.D. Ryman and W.B. Klimstra. 2011. Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence. Proc Natl Acad Sci USA, 108:16026-31.
- Daffis, S., K.J. Szretter, J. Schriewer, J. Li, S. Youn, J. Errett, T.Y. Lin, S. Schneller, R. Zust, H. Dong, V. Thiel, G.C. Sen, V. Fensterl, W.B. Klimstra, T.C. Pierson, R.M. Buller, M. Gale Jr, P.Y. Shi and M.S. Diamond. 2010. 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature, 468:452-6.
- Meier. K.C., C.L. Gardner, M.V. Khoretonenko, W.B. Klimstra and K.D. Ryman 2009. A mouse model for viscerotropic disease caused by yellow fever virus infection. PLoS Pathogens. Oct;5(10):e1000614. Epub 2009 Oct 9.
- Yin, J., C.L. Gardner, C.W. Burke, K.D. Ryman and W.B. Klimstra. 2009. Similarities and differences in antagonism of neuron alpha/beta interferon responses by Venezuelan equine and Sindbis alphaviruses. J. Virol. 83:10036-10047.