Molecular Microbiology and Immunology, malaria, transgenic mice, T-cells, memory, vaccines
Experiences & Accomplishments
Our current research focuses on the characterization of the cellular and molecular mechanisms underlying the induction of protective T-cell mediated immunity against malaria parasites. We generated strains of transgenic mice bearing T cell receptors specific for parasite antigens recognized by CD8+ or CD4+ T cells. Using these mice, we are currently conducting studies to characterize the molecular and genetic events involved in the development and maintenance of effector anti-parasite T cells, and the mechanisms by which CD4+ /CD8+ T cells interact during the development of immunity against infection. Our research combines in vivo immuno-physiology studies together with molecular and genetic approaches. Particular emphasis is given to research aimed at characterizing the mechanisms involved in tissue-trafficking of activated CD8+ T cells and identifying the nature of the molecular processes leading to the development of memory subsets.
These studies using a rodent parasite system provides the rationale and experimental basis for research aimed at developing an anti-malaria vaccine for humans. Furthermore, these rodent models are excellent systems for studying the general principles of protective immunity against intracellular pathogens, as they develop in vivo. These studies enhance our understanding of the immune system at the most fundamental level.
SELECTED PUBLICATIONS OF THE LAST EIGHT YEARS
Cockburn I.A., Sze-Wah Tse. Radtke AJ, Srinivasan P, Chen Y.C, Sinnis P and Zavala F 2011 Dendritic cells and hepatocytes use distinct pathways to process protective antigen from Plasmodium in vivo. PLoS Pathog March :7(3) e1001318
Overstreet M. G., Chen Y.C., Cockburn I. A., Tse S-W., and Zavala F. 2011 CD4+ T cells Modulate Expansion and Survival but not Functional Properties of Effector and Memory CD8+ T cells Induced by Malaria Sporozoites.. PLoS One Jan 4;6(1):e15948.
Palma C. Overstreet MG, Guedon JM, Hoiczyk E, Ward C, Karen K A., Zavala F, and Ketner G. 2011. Adenovirus Particles that Display the Plasmodium falciparum Circumsporozoite Protein NANP Repeat Induce Sporozoite-Neutralizing Antibodies in Mice. Vaccine Feb 11;29(8):1683-9.
Riley EM, Couper KN, Helmby H, Hafalla JC, de Souza JB, Langhorne J, Jarra WB, Zavala F. 2010 Neuropathogenesis of human and murine malaria.. Trends Parasitol. 2010 Jun;26(6):277-8.