William Klimstra, PhD

  • Professor
  • Immunology

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

Representative Publications

  • Christina L. Gardner, Chengqun Sun, Thomas Luke, Kanakatte Raviprakash, Hua Wu, Jin-an Jiao, Eddie Sullivan, Douglas S. Reed, Kate D. Ryman and William B. Klimstra. 2017. Antibody preparations from human transchromosomic cows exhibit prophylactic and therapeutic efficacy versus Venezuelan equine encephalitis virus. J.Virol. 91: e00226-17. PMCID: 5487544

  • Alan M. Watson, Annika Rose, Gregory Gibson, Christian Gardner, Douglas Reed, Peter Strick, Claudette St. Croix, William B. Klimstra1 and Simon Watkins1 2017. Ribbon scanning confocal imaging for high-speed high-resolution volume imaging of brain.  PLOS One. 12:e0180486 PMCID: 5501561   1. Authors contributed equally

  • LK Metthew Lam, Alan M. Watson, Kate D. Ryman and William B. Klimstra. 2018. Gamma-Interferon exerts a critical early restriction on replication and dissemination of yellow fever virus vaccine strain 17D-204. Nature Partner Vaccines 3:5. PMCID: 5780476.

  • Whitney C. Lane, Christina L. Gardner, Chengqun Sun, LK Metthew Lam, Alan M. Watson, Amy L. Hartman and William B. Klimstra. 2018. The efficacy of the interferon alpha/beta response against arboviruses is temperature dependent. mBio. 9:e00535-18  PMCID: 5915735.

  • Zhang, R, Kim A, Fox JM, Nair S, Basore K, Klimstra WB, Rimkunas R, Fong RH, Lin H, Poddar S, Crowe JE, Doranz BJ, Fremont BH, Diamond MS. 2018. Mxra8 is a receptor for multiple arthritogenic alphaviruses. Nature. 557:570-574. PCMID: 5970976.

  • Christopher M. Weiss, Derek W. Trobaugh, Chengqun Sun, Michael S. Diamond, Kate D. Ryman and William B. Klimstra. 2018. The interferon-induced exonuclease, ISG20, exerts antiviral activity through upregulation of antiviral effector proteins. mSphere. 3:e00209. PMCID: 6147134.

  • Arthur S. Kim, S. Kyle Austin, Christina L. Gardner, Adam Zuiani, Douglas S. Reed, Mark K. Slifka, David H. Fremont, William B. Klimstra1 and Michael S. Diamond1. 2018. Protective antibodies against eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 protein. Nature Microbiology ePub ahead of print. PMID 30455470.

  • S.S. Hasan, C. Sun, A.S. Kim, C.L. Chen, T. Klose, G. Buda, M.S. Diamond, W.B. Klimstra, M.G. Rosmann. 2018. CryoEM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization. Cell Reports epub Dec. 11, 2018 PMCID: 6302666.

  • Derek W. Trobaugh, Chengqun Sun, Douglas S. Reed, William B. Klimstra. 2019. Rational design of a live-attenuated eastern equine encephalitis virus vaccine through informed mutation of virulence determinants. PLOS Pathogens ePub PMID: 30742691.

  • Derek W. Trobaugh, Chengqun Sun, Christhina L. Gardner and Wiliam B Klimstra. 2019. Cooperativiety between miR142-3p binding sites in the eastern equine encephalitis virus 3’ untranslated region is critical to disease in mice. PLOS Pathogens 15:e1007867 PMID: 31658290.

  • Nishank Bhalla, Chengqun Sun, Christina L. Gardner, William B. Klimstra. 2019. Macromolecular synthesis shutoff resistance by myeloid cells is critical to IRF7-dependent systemic interferon alpha/beta induction after alphavirus infection. J. VIrol. Epub ahead of print. PMID: 31578290.