Jason F. Huntley, Ph.D.
Assistant Professor Director, BSL3 Laboratory
Francisella tularensis pathogenesis
Dr. Huntley’s laboratory studies the intracellular pathogen Francisella tularensis. Projects in the lab are focused on identifying bacterial virulence factors, examining how the bacteria bind to and invade host cells, analyzing changes in expression profiles inside host cells, and surveying the host immune responses to infection.
Francisella tularensis, the etiological agent of tularemia, is a Gram-negative intracellular bacterium that causes rapid, fatal disease in a number of mammalian species, including humans. F. tularensis is well-recognized as one of the most dangerous bacterial pathogens known because of its low infectious dose (< 10 organisms), ease of aerosolization, multiple routes of infection, and ability to induce severe disease and death. Additional causes for concern come from reports that Soviet scientists engineered antibiotic- and vaccine-resistant strains of F. tularensis through the 1990s. Given these considerations, F. tularensis has been recognized as a potential bioweapon and thus has been designated as a Tier 1 select agent by the CDC. Despite a relatively recent surge in F. tularensis research, surprisingly little has been reported, or is known, about the molecules that the bacterium uses to bind to and invade host cells, to survive inside host cells, or to evade immune detection. As compared with other bacterial pathogens, the robust infectivity and pathogenesis of F. tularensis suggest that it has unique bacterial effectors and virulence mechanisms. To date, no secreted proteins or functional secretion systems have been identified from the virulent strains of F. tularensis, arguing that intracellularly-induced outer membrane proteins (OMPs) are likely involved in initiating and sustaining F. tularensisinfection and disease pathogenesis. Indeed, OMPs have been shown to be virulence factors in many bacterial pathogens and, for this reason, are ideal vaccine targets. Given these considerations, research projects in the Huntley laboratory are currently underway to: (1) Identify F. tularensis OMPs up-regulated during mammalian infection; (2) Create OMP-deficient F. tularensis mutants to confirm the roles of in vivo-upregulated OMPs as virulence factors; (3) Characterize the function of these OMPs in pathogenesis; (4) Identify host cell molecules that F. tularensis OMPs interact with to promote disease; (5) Define OMP-specific immune responses that protect against F. tularensis infection. These projects are designed to answer fundamental questions about F. tularensis virulence and have practical applications for the development of safe, efficacious vaccines to prevent F. tularensis infection and disease.
Dr. Huntley received his M.S. in Veterinary Microbiology in 1999 from Iowa State University
under the mentorship of Drs. Kenneth B. Platt (Iowa State University) and Steve R.
Bolin (National Animal Disease Center, ARS, USDA). Dr. Huntley received his Ph.D.
in Veterinary Pathology in 2004 from Iowa State University under the mentorship of
Drs. Mark R. Ackermann (Iowa State University) and Judith R. Stabel (National Animal
Disease Center, ARS, USDA). Dr. Huntley completed post-doctoral training at The University
of Texas Southwestern Medical Center in Dallas in 2010 in the laboratory of Michael
V. Norgard. Dr. Huntley joined the Department of Medical Microbiology and Immunology
at the University of Toledo in July 2010.
Current Grant Funding:
NIH - R01 - Preclinical Development of a Tularemia Vaccine, 3/15/2011-2/28/2016
Department of Defense – Defense Threat Reduction Agency – Adjuvanted Nanolipoprotein Particles for use in Enhancing the Protective Efficacy of Francisella tularensis Membrane Protein Antigens. 10/1/2014 – 9/30/2017
Curtis MM, Russell R, Moreira CG, Adebesin AM, Wang C, Williams NS, Taussig R, Stewart D, Zimmern P, Lu B, Prasad RN, Zhu C, Rasko DA, Huntley JF, Falck JR, Sperandio V. (2014). QseC Inhibitors as an Antivirulence Approach for Gram-Negative Pathogens. MBio. 5(6). pii: e02165-14. http://www.ncbi.nlm.nih.gov/pubmed/25389178
Ren G, Champion MM, Huntley JF. (2014). Identification of disulfide bond isomerase substrates reveals bacterial virulence factors. Mol Microbiol. 94(4):926-44. http://www.ncbi.nlm.nih.gov/pubmed/25257164
Mahawar M, Atianand MK, Dotson RJ, Mora V, Rabadi SM, Metzger DW, Huntley JF, Harton JA, Malik M, Bakshi CS. (2012). Identification of a novel Francisella tularensis factor required for intramacrophage survival and subversion of innate immune response. J Biol Chem. 287(30):25216-29.
Huntley JF, Robertson GT, and Norgard MV. (2010). Method for the isolation of Francisella tularensis outer membranes. J Vis Exp. 2010 Jun 29;(40). pii: 2044. doi: 10.3791/2044.
Huntley JF, Conley PG, Rasko DA, Hagman KE, Apicella MA, and Norgard MV. (2008). Native outer membrane proteins protect mice against pulmonary challenge with virulent Type A Francisella tularensis. Infect. Immun. 76(8): 3664-3671.
Rasko DA, Moreira CG, Li DR, Reading NC, Ritchie JM, Waldor MK, Williams N, Taussig R, Wei S, Roth M, Hughes DT, Huntley JF, Fina MW, Falck JR, and Sperandio V. (2008). Targeting QseC signaling and virulence for antibiotic development. Science. 321:1078-1080.
Kiss K, Liu W, Huntley JF, Norgard MV, and Hansen EJ. (2008). Characterization of fig operon mutants of Francisella novicida U112. FEMS Microbiol. Lett. 285(2): 270-277.
Huntley JF, Conley PG, Hagman KE, and Norgard MV. (2007). Characterization of Francisella tularensis outer membrane proteins. J. Bacteriol. 189(2): 561-574.
Huntley JF, Stabel JR, Paustian ML, Reinhardt TA, and Bannantine JP. (2005). Expression library immunization confers protection against Mycobacterium avium subsp. paratuberculosis infection . Infect. Immun. 73(10): 6877-6884.
Huntley JF, Whitlock RH, Bannantine JP, and Stabel JR. (2005). Comparison of diagnostic detection methods for Mycobacterium avium subsp. paratuberculosis from North American bison. Vet. Pathol. 42(1): 42-51.
Huntley JF, Stabel JR, and Bannantine JP. (2005). Immunoreactivity of the Mycobacterium avium subsp. paratuberculosis 19-kDa lipoprotein. BMC Microbiol. 5(1): 3-26.
Bannantine JP, Huntley JF, Miltner E, Stabel JR, and Bermudez LE. (2003). The Mycobacterium avium subsp. paratuberculosis 35kDa protein plays a role in invasion of bovine epithelial cells. Microbiology 149(8): 2061-2069.