Dr. Denkers is a Professor in the Department of Microbiology and Immunology and has been associated with the department since 1995. He received the BS degree in Biology from the University of Washington in 1982. He then received his PhD from the University of Wisconsin-Madison in 1990 studying molecular biology. After spending 5 years at the NIH, Dr. Denkers joined the Department of Microbiology and Immunology at Cornell. He currently has funding from NIH to study molecular and cellular immunity to Toxoplasma gondii.
We are interested in how the immune system recognizes and combats infection, how pathogens evade immunity, and how dysregulated responses lead to immunopathology. The microorganism we study is Toxoplasma gondii, a highly successful intracellular protozoan parasite that normally results in asymptomatic infection, but that causes life-threatening disease in immunocompromised patients and during congenital infection. There are currently two broad lines of investigation in our lab.
1. Mucosal immune response to infection
We are examining the early immune response to Toxoplasma in the small intestine, which is the normal entry point for the parasite. We are investigating how T lymphocytes and cells of the innate immune system interact to provide protective immunity in this location. Areas of research include determining the early activation signals involved in recognition of infection, and defining the key chemokines and cytokines required for an effective immune response. Closely related to this line of research, we are investigating how T. gondii may under certain conditions trigger severe proinflammatory pathology in the small intestine. We are interested in the molecules that signal onset of lesions and the cells, cytokines and chemokines that cause disease.
2. Manipulation of host signal transduction during intracellular infection
Early targets of infection are macrophages and dendritic cells, which also appear to serve as vehicles of dissemination in the host. This is paradoxical because these cells are at the same time involved in parasite killing and initiation of immunity. We have found that Toxoplasma potently suppresses induction of proinflammatory cytokines such as IL-12 and TNF-a by dendritic cells and macrophages. Ongoing research in our lab is examining how Toxoplasma seizes control of key signal transduction pathways to suppress cytokine gene induction and promote its own survival. We are investigating the parasite molecules involved, how they function, and we are determining the in vivo consequences of this interaction.
Dr. Denkers is a member of the following Graduate Fields:
Denkers, E.Y., Bzik, D. J., Fox, B. A. and Butcher, B. A. 2012. An inside job: Hacking into JAK/STAT signaling cascades by the intracellular protozoan Toxoplasma gondii. Infect. Immun. 80: 476-48
Mahamed, D., Mills, J., Egan, C.E., Denkers, E.Y. and M.S. Bynoe. 2012. CD73-generatated adenosine facilitates Toxolasma gondii differentiation to long-lived tissue cysts in the central nervous system. Proc. Natl. Acad. Sci. 109: 16312-16317.
Cohen, S.B., Maurer, K.J., Egan, C.E., Oghumu, S., Satoskar, A.R., and E.Y. Denkers. 2013. CXCR3-dependent CD4+ T cells are required to activate inflammatory monocytes for defense against intestinal infection. PLoS-Pathogens. 9: e1003706.
Cohen, S.B. and E.Y. Denkers. 2014. Border maneuvers: Deployment of mucosal immune defenses against Toxoplasma gondii. Mucosal Immunol. doi: 10.1038/mi.2014.25.