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 Associate Professor
Lewis Hall, #3184
Office: (757) 446-5677
Email:
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Teaching:
Graduate Students
- Introduction to the Research Literature
- Biomedical Sciences Seminar (Journal Club)
- Concepts in Research Design
- Research Techniques
- Advanced Molecular and Cellular Techniques
- Current Topics in Molecular Biology
- Animal Virology
- Advanced Cell Biology
- Advanced Proteomics
Medical Students
- Medical Microbiology and Immunology, Course Director
Medical Masters
- Library Thesis Research Paper
Biomedical Sciences Program Track: Molecular Integrative Biosciences (MIB)
Education
- B.A., Earlham College, Richmond, IN
- Ph.D., Pennsylvania State University School of Medicine, Hershey, PA
- Postdoctoral Training, The Scripps Research Institute, La Jolla, CA
Research Interests
Dr. Krishna's laboratory studies the human astroviruses (HAstVs), a family of non-enveloped, icosahedral RNA viruses that cause gastroenteritis, predominantly in infants. Eight HAstV serotypes have been identified with a worldwide distribution. While the HAstVs represent a significant public health concern, very little is known about the pathogenesis and host immune response to this virus. We have demonstrated that HAstV-1 virions, specifically the viral capsid protein, suppress the complement system, a fundamental component of the innate immune response against pathogens in vertebrates. This is achieved by the capsid binding to the first component of the complement pathway, C1q. Binding of C1q by the capsid inhibits complement activation and its downstream effects (e.g., inflammation, cell lysis, phagocytosis, etc.). We are interested in determining the mechanism whereby the capsid protein inhibits complement activation and the role of C1q binding in the pathogenesis and life-cycle of the Astroviridae.
A second area of interest for our laboratory is the development of the astrovirus capsid protein as a therapeutic for complement-mediated disease. Whilst the human complement system represents a front-line defense against pathogens such as bacteria and viruses, its uncontrolled activation can lead to severe pathology in many different inflammatory and autoimmune disorders with an immune component such as systemic lupus erythematosis, rheumatoid arthritis, inflammatory bowel disease, ischemia-reperfusion injury (myocardial infarct, stroke), glomerulonephritis, adult respiratory distress syndrome, transplant rejection, graft versus host disease and burn injuries.
Currently there are no effective complement inhibitors on the market. Given the very potent inhibition of human astrovirus coat protein on the complement system, we are currently interested in developing this protein into a therapeutic compound as method for regulating aberrant complement activity.
Selected Publications
- Gronemus J.Q., Hair P.S., Crawford K.B., Nyalwidhe J.O., Cunnion K.M., Krishna, N.K. 2010. Potent inhibition of the classical pathway of complement by a novel C1q-binding peptide derived from the human astrovirus coat protein. Molec. Immunol., 48(1-3):305-313.
- Hair P.S., Gronemus J.Q., Crawford K.B., Salvi V.P., Cunnion K.M., Thielens NM, Arlaud GJ, Rawal N and Krishna NK. 2010. Human astrovirus coat protein binds C1q and MBL and inhibits the classical and lectin pathways of complement activation. Molec. Immunol. 47(4):792-798.
- Krishna N.K. and K.M. Cunnion. 2008. Human astrovirus coat protein: a novel C1 inhibitor. Adv. Exp. Med. Biol. 632:237-251.
- Bonaparte, R.S., P.S. Hair, D. Banthia, D.M. Marshall, K.M. Cunnion and N.K. Krishna. 2008. Human astrovirus coat protein inhibits serum complement activation via C1, the first component of the classical pathway. J. Virol, 82(2):817-827.
- Krishna, N.K. 2005. Identification of structural domains involved in astrovirus capsid biology. Viral Immunol., 18(1):17-26.
- Venter, P.A., N.K. Krishna and A. Schneemann. 2005. Capsid protein synthesis from replicating RNA directs specific packaging of the genome of a multipartite, positive strand RNA virus. J. Virol., 79:6239-6248.
- Karabekian, Z., L.K. Hanson, J.S. Slater, N.K. Krishna, L.L. Bolin, J.A. Kerry and A.E. Campbell. 2005. Complex Formation Among Murine Cytomegalovirus US22 Proteins Encoded by M139, M140, and M141. J. Virol., 79:3525-3535.
- Krishna NK, Marshall D, Schneemann A. 2003. Analysis of RNA packaging in wild-type and mosaic protein capsids of Flock House virus using recombinant baculovirus. Virology, 305:10-24.
- Taylor, D.J., N.K. Krishna, M.A. Canady, A. Schneemann and J.E. Johnson. 2002. Large scale, pH dependent, quaternary structure changes in a RNA virus capsid are reversible in the absence of subunit auto-proteolysis. J. Virol., 76:9972-9980.
- Tang, L., C.S. Lin, N.K. Krishna, M. Yeager, A. Schneemann and J.E. Johnson. 2002. Virus-like particles of a fish nodavirus display a capsid subunit domain organization different from that of insect nodaviruses. J. Virol., 76:6370-6375.
- Lin, C.S., M.W. Lu, L. Tang, W. Liu, C.B. Chao, C.J. Lin, N.K. Krishna, J.E. Johnson and A. Schneemann. 2001. Characterization of virus-like particles assembled in a recombinant baculovirus system expressing the capsid protein of a fish nodavirus. Virology, 290:50-58.
- Krishna, N.K. and J.W. Wills. 2001. Insertion of capsid proteins from nonenveloped viruses into the retroviral budding pathway. J. Virol., 75:6527-6536.
Patents
- Title: "Peptide compounds to regulate the complement system." Provisional application filed 21 July, 2010. Inventors: Krishna N.K. and Cunnion K.M.
- "Methods for regulating complement cascade proteins using astrovirus coat protein and derivatives thereof." Provisional application filed 16 June, 2006. Inventors: Krishna, N.K. and Cunnion K.M.
- International Patent Application filed under the Patent Corporation Treaty, "Nodavirus-VLPs Immunization Composition." Provisional application filed May 29, 2005. Inventors: Thiery R., Baud M., Cabon J., Cozien J., Lamour F., Lin C.S., Krishna N.K., Johnson J.E. and Schneemann A.
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