People

Michael Oglesbee

DVM, PhD, Diplomate ACVP

Professor; Director, Infectious Diseases Institute; Faculty Lead, Infectious Diseases Discovery Theme; Director, College Summer Research Program; Director, Infectious Diseases Signature Program

Contact

oglesbee.1@osu.edu (614) 292-9672 Goss Laboratory
1925 Coffee Road
Columbus, OH 43210
Map Link

Department

Veterinary Biosciences

Center For Retrovirus Research

Professional Training and experience

  • DVM, (summa cum laude), The Ohio State University
  • PhD The Ohio State University
  • Diplomate, American College of Veterinary Pathologists

Research Interests

  • Neuropathology
  • The role of heat shock proteins in viral replication, antiviral immunity, and ​​​​​​neuroinflammation.     

Named a Fellow by the American Association for the Advancement of Science in recognition of contributions to our understanding of virus-heat shock protein interactions related to infection, virulence and impact on innate and adaptive antiviral immunity.

Research Summary

The cellular stress response is characterized by the production of heat shock proteins (HSP) that mediate cell recovery from and protection against potentially lethal injury. This protective role is well documented in metabolic, degenerative, and ischemic brain injury, but our group was the first to address how these same HSP influence a virus’ ability to spread and cause disease in the nervous system. 

Research performed in my laboratory showed that the major inducible 70 kDa heat shock protein (hsp70) is induced by and supports intracellular replication of viruses belonging to diverse families, with specific focus on measles and canine distemper virus (paramyxoviruses) and vesicular stomatitis virus (a rhabdovirus). Paradoxically, this virus-hsp70 interaction is protective in mouse models of viral neurovirulence, enhancing T cell mediated immune clearance in an interferon β (IFN-β)-dependent manner. Protection reflects early release of hsp70 from viable infected neurons and induction of strong innate immune responses in uninfected brain macrophages, including the induction of IFN-β through Toll-like receptor 4. Potency of the response is inherent in the fact that hsp70 is released at a time when pathogen-associated molecular patterns (PAMPs) are in low abundance, and that the innate response is driven by uninfected cells, free from viral interference. Release of hsp70 from viable cells is primarily exosomal, and infection enhances total exosome release and hsp70 content on the surface of exosomes. Exosome content of hsp70 reflects levels of hsp70 in the infected cell. Findings have broad virological relevance and support a protective role for fever, a potent stimulus for hsp70 induction. While protective in the context of microbial infection, recent findings support potential untoward effects of inappropriate extracellular hsp70 release in non-infectious neuroinflammatory conditions.

Ongoing collaborative research support is provided in the general areas of neurovirology and neuropathology.

Director, Summer Research Program for Veterinary Medical Students

The program provides intensive research experiences for veterinary medical students interested in research. Individuals are selected each year based upon a research proposal developed by the student in collaboration with their intended faculty mentor. Students perform the bulk of the research during the summer, present research findings at both local (e.g., College of Veterinary Medicine Research Day) and national meetings (e.g., Veterinary Scholars Symposium, or a scientific meeting within their field of study). Funding is provided from NIH, Boehringer Ingelheim, department and college monies, and development funds. Dr. Oglesbee is director of the NIH T53 (Short Term Research Training for Veterinary Students) supporting this program, now in it’s third renewal. The T35 supports 10 students per year. 

Director, Infectious Diseases Institute, The Ohio State University

The Ohio State University Infectious Diseases Institute (IDI) was established in 2017 to build upon the successes of previous university programs* and accelerate infectious disease research and education with a more integrated structure. Designed to be inclusive and nimble, IDI supports researchers and educators throughout the university with resources, connections and opportunities that strengthen partnerships with industry, government and other organizations. Emphasis is placed on interdisciplinary networks in five programmatic areas, consisting of over 230 faculty representing eleven colleges and the Research Institute at Nationwide Children’s Hospital. These programs are antimicrobial resistance; ecology, epidemiology and population health; host defense and microbial biology; microbial communities; viruses and emerging pathogens.
*The Institute was an outgrowth of the Discovery Theme in Infectious Disease. Dr. Oglesbee is the faculty lead for this effort, initiated in 2014.

Director, Infectious Diseases Signature Program, College of Veterinary Medicine

Faculty in the College of Veterinary Medicine play a significant role in the Infectious Diseases Institute, with faculty playing leadership roles in half of the Institute programmatic areas and total tenure track faculty representing 16% of the university infectious diseases community. The role of the director is to ensure alignment between the four programs within the college community that link with those of the institute:  antimicrobial resistance; ecology, epidemiology and population health; host defense and microbial biology; viruses and emerging pathogens. Such alignment enables the college community to better leverage university resources and engage interdisciplinary research networks in ways that enhance impact. College investments launched the Infection Control and Antibiotic Stewardship Program in the Veterinary Medical Center, and have increased capacity of our Gnotobiotic Life Laboratory.

Teaching

  • Veterinary Medical Professional Curriculum
    • Didactic and laboratory instruction in neuropathology, histology of the nervous system, and applied pathology
  • Graduate Education
    • Didactic and laboratory instruction in neuropathology

University Memberships

  • Center for Retrovirus Research
  • NCI-Designated Comprehensive Cancer Center, The Arthur James Cancer Hospital and Research Institute 

Publications

Selected Publications (from 109)

  • von Rüden, E-L., Wolf, F., Keck, M., Gualtieri, F., Oglesbee, M., Potschka, H. (2018). Genetic modulation of HSPA1A accelerates kindling progression and exerts pro-convulsant effects. Neuroscience 386:108-120.
  • Moore, S.A., Oglesbee, M. (2015). Spinal cord ependymal responses to naturally occurring traumatic spinal cord injury in dogs. Veterinary Pathology 52(6):1108-1117.
  • Ma, Y., Duan, Y., Wei, Y., Liang, X., Niewiesk, S., Oglesbee, M., Li, J. (2014). Heat shock protein 70 enhances mucosal immunity against human norovirus when co-expressed from a vesicular stomatitis viral vector. Journal of Virology 88(9):5122-37.
  • Kim, M.Y., Ma, Y., Zhang, Y., Li, J., Shu, Y., Oglesbee, M. (2013). Hsp70-dependent antiviral immunity against cytopathic neuronal infection by vesicular stomatitis virus. Journal of Virology 87(19):10668-10678.
  • Kim, M.Y., Shu, Y., Carsillo, T., Zhang, J., Yu, L., Peterson, C., Longhi, S., Girod, S., Niewiesk, S., Oglesbee, M. (2013). Hsp70 and a novel axis of type I interferon-dependent antiviral immunity in the measles virus-infected brain. Journal of Virology 87(2):998.
  • Shu, Y., Habchi, J., Costanzo, S., Padilla, A., Brunel, J., Gerlier, D., *Oglesbee, M., *Longhi, S. (2012). Plasticity in structural and functional interactions between the phosphoprotein and nucleoprotein of measles virus. Journal of Biological Chemistry 287(15):11951-67. *co-senior authors
  • Moore, S., Kim, M.Y., Maiolini, A., Tipold, A., Oglesbee, M. (2012). Extracellular hsp70 release in canine steroid responsive meningitis-arteritis. Veterinary Immunology and Immunopathology 145(1-2):129-33.
  • Kim, D., Huey, D., Oglesbee, M., Niewiesk, S. (2011). Insights into the regulatory mechanism controlling the inhibition of vaccine-induced seroconversion by maternal antibodies. Blood 117(23):6143-51.
  • Oglesbee, M., Niewiesk, S. (2011). Measles virus neurovirulence and host immunity. Future Virology 6(1):85-99
  • Longhi, S., Oglesbee, M. (2010). Structural disorder within the measles virus nucleoprotein and phosphoprotein. Protein and Peptide Letters 17(8):961-78.
  • Couturier, M., Buccellato, M., Costanzo, S., Bourhis, J.M., Shu, Y., Nicaise, M., Desmadrill, M., Flaudrops, C., Longhi, S., Oglesbee, M.  (2010). High affinity binding between hsp70 and the C-terminal domain of the measles virus nucleoprotein requires an hsp40 co-chaperone. Journal of Molecular Recognition 23(3):301-15.
  • Carsillo, T., Carsillo, M., Traylor, Z., Rajala-Schultz, P., Popovich, P., Niewiesk, S., Oglesbee, M. (2009). Major histocompatibility complex haplotype determines hsp70-dependent protection against measles virus neurovirulence. Journal of Virology 83(11):5544-5555.
  • Awad, H., Suntres, Z., Heijmans, J., Smeak, D., Bergdall-Costell, V., Cristofi, F.L., Magro, C., Oglesbee, M. (2008). Intracellular and extracellular expression of the major inducible 70 kDa heat shock protein in experimental ischemia-reperfusion injury of the spinal cord. Experimental Neurology 212:275-284.
  • Carsillo, T., Traylor, Z., Choi, C., Niewiesk, S., Oglesbee, M. (2006). Hsp72, a host determinant of measles virus neurovirulence. Journal of Virology 80(22):11031-11039.
  • Carsillo, T., Zhang, X., Vasconcelos, D., Niewiesk, S., Oglesbee, M. (2006). A single codon in the nucleocapsid protein C-terminus contributes to in vitro and in vivo fitness of Edmonston measles virus. Journal of Virology 80(6): 2904-2912.
  • Oglesbee, M.J., Herdman, A.V., Passmore, G.G., Hoffman, W.H. (2005). Diabetic ketoacidosis increases extracellular levels of the major inducible 70 kDa heat shock protein. Clinical Biochemistry 38(10):900-4.
  • Zhang, X., Bhouris, J.-M., Longhi, S., Carsillo, T., Buccellato, M., Morin, B., Canard, B., Oglesbee, M. (2005). Hsp72 recognizes a P binding motif in the measles virus N protein C-terminus. Virology 337:162-174.
  • Carsillo, T., Carsillo, M., Niewiesk, S., Vasconcelos, D., Oglesbee, M. (2004). Hyperthermic pre-conditioning promotes measles virus clearance from brain in a mouse model of persistent infection. Brain Research 1004:73-82.
  • Zhang, X., Glendening, C., Linke, H., Parks, C.L., Brooks, C., Udem, S.A., Oglesbee,  M. (2002). Identification and characterization of a regulatory domain on the carboxyl terminus of the measles virus nucleocapsid protein. Journal of Virology 76(17):8737-8746.
  • Oglesbee, M.J., Pratt, M., Carsillo, T. (2002). A role for heat shock proteins in the immune response to measles virus infection. Viral Immunology 15(3):399-416.
  • Oglesbee, M.J., Alldinger, S., Vasconcelos, D., Diehl, K., Shinko, P., Baumgärtner, W., Tallman, R., Podell, M. (2002). Intrinsic thermal resistance of the canine brain. Neuroscience 113(1):55-64.
  • Diehl, K.A., Crawford, E., Shinko, P.D., Tallman, R.D., Oglesbee, M.J. (2000). Alterations in hemostasis associated with hyperthermia in a canine model. American Journal of Hematology 64(4):262-270.
  • Oglesbee, M.J., Diehl, K., Crawford, E., Kearns, R., and Krakowka, S. (1999). Whole body hyperthermia: effects upon canine immune and hemostatic functions. Veterinary Immunology and Immunopathology 69:185-199.
  • Kearns, R.J., Ringler, S., Krakowka, S., Tallman, R. Sites, J., Oglesbee, M.J. (1999). The effects of extracorporeal whole body hyperthermia on the functional and phenotypic features of canine peripheral blood mononuclear cells. Clinical and Experimental Immunology 116:188-192.
  • Vasconcelos, D., Cai, X.H., Oglesbee, M.J. (1998). Constitutive over-expression of the major inducible 70 kDa heat shock protein mediates large plaque formation by measles virus. Journal of General Virology 79:2239-2247.
  • Heller, M., Vasconcelos, D., Cummins, J., Oglesbee, M. (1998). Interferon-α inhibits the emergence of cellular stress response-dependent morbillivirus large plaque variants. Antiviral Research 38:195-207.
  • Vasconcelos, D., Norrby, E., Oglesbee, M. (1998). The cellular stress response increases measles virus-induced cytopathic effect. Journal of General Virology 79:1769-1773.
  • Liu, Z., Huntley, C.C., De, B.P., Das, T., Banerjee, A.K., Oglesbee, M. (1997). Phosphorylation of canine distemper virus P protein by protein kinase C-ζ and casein kinase II. Virology 232(1): 198-206.
  • Andrews, J., Newbound, G., Oglesbee, M., Brady, J., Lairmore, M. (1997). The cellular stress response enhances HTLV-1 basal gene expression through the basal core promoter of the long terminal repeat. Journal of Virology 71(1): 741-745.
  • Oglesbee, M.J., Liu, Z., Kenney, H., Brooks, C. (1996). The highly inducible member of heat shock proteins increases canine distemper virus polymerase activity. Journal of General Virology 77:2125-2135.
  • Andrews, J., Oglesbee, M., Trevino, A., Guyot, D., Newbound, G., Lairmore, M. (1995). Enhanced human T cell lymphotrophic virus type I expression following induction of the cellular stress response. Virology 208:816-820.
  • Oglesbee, M., and Krakowka, S. (1993). The cellular stress response induces selective intranuclear trafficking and accumulation of morbillivirus major core protein. Laboratory Investigation 68(1):109-117.
  • Oglesbee, M., Kenney, H., Kenney, T., and Krakowka, S. (1993). Enhanced production of morbillivirus gene-specific RNAs following induction of the cellular stress response in stable persistent infection. Virology 192:556-567.
  • Oglesbee, M. (1992). Intranuclear inclusions in paramyxovirus-induced encephalitis: evidence for altered nuclear body differentiation. Acta Neuropathologica 84:407-415.
  • Oglesbee, M., Ringler, S., and Krakowka, S. (1990). Interaction of canine distemper virus nucleocapsid variants with 70k heat shock proteins. Journal of General Virology 71:1585-1590.

  • Oglesbee, M., Tatalick, L., Rice, J., and Krakowka, S. (1989). Isolation and characterization of canine distemper virus nucleocapsid variants. Journal of General Virology 70:2409-2419.

     

    Book Chapters

  • Oglesbee, M. (2007). Nucleocapsid Interactions with the major inducible 70 kDa heat shock protein. In: Longhi, S. (Editor), Measles Virus Nucleoprotein. Nova Scientific Publishers, Inc., Hauppauge NY.
  • Buccellato, M., Carsillo, T., Oglesbee, M. (2007). Heat shock protein expression in brain: a protective role spanning intrinsic thermal resistance to host defense against neurotropic viruses. In: Sharma, H. (Editor), Progress in brain Research, Volume 162, Neurobiology of Hyperthermia, Elsevier.
  • Niewiesk, S., Oglesbee, M. (2013). Paramyxoviridae, Filoviridae, and Bornaviridae. In: McVey, D.S., Kennedy, M., and Chengappa, M.M. (Editors), Veterinary Microbiology, 3rd Edition. Wiley-Blackwell, Ames, Iowa.
  • Oglesbee, M., Niewiesk, S. (2016). Pathogenesis of Viral Infections and Diseases. In: MacLachlan, N.J., and Dubovi, E.J. (Editors), Fenner’s Veterinary Virology, 5th Edition. Elsevier, San Diego, CA.
  • Oglesbee, M., Kim, M.Y., Shu, Y., Longhi, S. (2019). Extracellular Hsp70, Neuroinflammation and Protection against Viral Virulence. In: Asea, A.A., and Kaur, P. (Editors), Chaperokine Activity of Heat Shock Proteins. Heat Shock Proteins Volume 16, Springer Nature International Publishers, Dordrecht, Netherlands.