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Eric Y. Denkers

 Eric Denkers. Professor

Professor of Immunology

Cornell University College of Veterinary Medicine
C5 165 Veterinary Medical Center
E-mail: eyd1@cornell.edu
Phone: 607-253-4022

PhD (University of Wisconsin - Madison)


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.


 Research Interests | Graduate Fields | Lab Members | Related Links | Selected References

Research Interests

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.

A shows the small intestine of a wild-type mouse infected with a high dose of T. gondii.  Bshows mice lacking the chemokine receptor CCR2 are resistant to this damage   CCR2 null mice are resistant to
  Toxoplasma-induced intestinal damage.
  Panel A shows the small intestine of a
  wild-type mouse infected with a high
  dose of T. gondii. A dysregulated
  proinflammatory cytokine response
  results in severe damage to the
  intestine. In panel B, mice lacking the
  chemokine receptor CCR2 are resistant
  to this damage and normal intestinal
  architecture is maintained during
 
Toxoplasma infection.

 

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.

Proliferation of parasites inside an infected cell 

  Proliferation of parasites inside an infected cell.
  Parasites (in green) invade the cell and
  take control of several intracellular signaling
  cascades. Proliferation of tachyzoites continues
  until the host cell ruptures, releasing invasive
  parasites.
  The host cell actin fibers appear in red.   
 


 

 

 


Graduate Fields

Dr. Denkers is a member of the following Graduate Fields:

dot Comparative Biomedical Sciences
dot Immunology and Infecious Disease



Lab Members

Barbara Butcher, Senior Research Associate
Sara Cohen, Graduate Student
Anne Schneider, Graduate Student
Kirk Maurer, Assistant Adjunct Professor
Mozammal Hossain, Technical Support

 


Related Links

 


Selected References

Egan, C. E., Maurer, K. J., Cohen, S. B., Mack, M., Davis, F. C., Simpson, K. W., and E. Y. Denkers. 2011. Synergy Between Intraepithelial Lymphocytes and Lamina Propria T Cells Drives Inflammation During Intestinal Infection.Mucosal Immunol. 4: 658-670

Butcher, B. A., Fox, B. A.,Rommereim, L. M., Kim, S. G., Maurer, K. J., Yarovinsky, F., Herbert, D. R., Bzik, D. J., and E. Y. Denkers. 2011. Toxoplasma gondii rhoptry protein ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS-Pathogens. 7: e1002236.

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.