Malaria is caused by protozoan parasites belonging to the genus Plasmodium. It is transmitted to humans in the form sporozoites via the bite of an infected mosquito. Sporozoites first infect the liver where they undergo differentiation and division to produce thousands of exo-erythrocytic forms. The exo-erythrocytic forms exit the liver and enter the bloodstream where they infect red-blood cells. The life-cycle is completed in the midgut of the mosquito where the parasites give rise once again to sporozoites.
My laboratory studies the sporozoite stages and their development in the liver. This is a multi-step process requiring several parasite proteins. Using the tools of molecular genetics and cell biology, we have identified some off these molecules and are studying the mechanism of their action. We have shown that a cGMP-dependent protein kinase is required for the parasite's exit from the liver. Sporozoites lacking this kinase infect the liver normally, develop into exo-erythrocytic forms but these exo-erythroctyic forms do not enter the bloodstream. The developmentally arrested exo-erythroctyic forms provoke a strong immune response from the host that protects against subsequent sporozoite infection. We are currently dissecting the parasite's cGMP signaling pathway and studying the nature of the immune response elicited by developmentally arrested exo-erythroctyic forms. This knowledge will facilitate the development of novel therapies against malaria.
- Panchal D and Bhanot P. (2010) Activity of a tri-substituted pyrrole in inhibiting sporozoite invasion and blocking malaria infection. Antimicrobial Agents and Chemotherapy 54(10):4269-74.
- Falae A., Combe A., Amaladoss A., Carvalho T., Menard R., Bhanot P. (2010) Role of Plasmodium berghei cGMP-dependent protein kinase in late liver stage development. Journal of Biological Chemistry 285(5): 3282-3288.
- Ono T., Cabrita-Santos L., Leitao R., Bettiol E., Purcell L.A., Diaz-Pulido O., Andrews L.B., Tadakuma T., Bhanot P., Mota M.M., Rodriguez A. (2008) Adenylyl cyclase alpha and cAMP signaling mediate Plasmodium sporozoite apical regulated exocytosis and hepatocyte infection. PLoS Pathogens 4(2): e1000008.
- Bhanot P., Schauer K., Coppens I. and Nussenzweig V. (2005) A surface phospholipase is involved in the migration of Plasmodium sporozoites through cells. Journal of Biological Chemistry 280(8): 6752-60.
- Wang Q., Brown S., Roos, D.S., Nussenzeig V. and Bhanot P. (2004) Transcriptome of axenic liver stages of Plasmodium yoelii. Molecular and Biochemical Parasitology 137(1): 161-8.
- Bhanot P., Frevert U., Nussenzweig V. and Persson C. (2003) Defective sorting of the Thrombospondin related anonymous protein (TRAP) inhibits Plasmodium infectivity. Molecular and Biochemical Parasitology 126(2): 263-73.
- Persson C. Oliveira G., Sultan A., Bhanot P., Nardin E. and Nussenzweig V. (2002) A hybrid Plasmodium berghei parasite is a new tool to evaluate the efficacy of pre-erythrocytic P. falciparum malaria vaccines. Journal of Immunology 169(12): 6681-5.
- Bhanot P. and Nussenzweig V. (2002) Plasmodium yoelii sporozoites infect Syndecan-1 deficient mice. Molecular and Biochemical Parasitology 123(2): 143.
- Bhanot P., Fish M., Jemison J., Nusse R., Nathans J. and Cadigan K.M. (1999) Frizzled and Frizzled-2 function as redundant receptors for Wingless during Drosophila embryonic development. Development 126(18): 4175-86.
- Andrew D.J., Baig A., Bhanot P., Smolik S.M. and Henderson K.D. (1997) The Drosophila dCREB-A gene is required for dorsal/ventral patterning of the larval cuticle. Development 124(1): 181-193.
- Bhanot P., Brink M., Samos C.H., Hsieh J.C., Wang Y., Macke J.P., Andrew D., Nathans J. and Nusse R. (1996) A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382(6588): 225-230.
Training and Positions
1993 B.A. in Biochemistry, Mount Holyoke College South Hadley, MA
1999 Ph.D. in Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD
2000-2004 Postdoctoral Fellow in Parasitology, New York University School of Medicine, New York, NY