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Prakash Srinivasan, PhD

  • Assistant Professor

Departmental Affiliations

Contact Information

615 N. Wolfe Street
Baltimore, Maryland 21205

443-287-3097
410-955-0105

View Current Courses

Education

PhD, Case Western Reserve University, 2007
MSc, St. Joseph's College, 1998

Overview

Malaria caused by Plasmodium falciparum remains one the most serious infectious diseases infecting over 200 million people and causing nearly 500,000 deaths every year, mostly in young children. Clinical disease is caused by the exponentially growing parasites within the red blood cells (RBCs). We study the dynamic processes regulating successful parasite entry into and exit from host cells. Our goal is to better understand the molecular mechanisms regulating some of the important biological processes outlined below. To address these questions we use complementary approaches encompassing conditional genome editing techniques, live cell imaging, high throughput screening, biochemistry and proteomics.

1. Identifying parasite and host factors regulating merozoite egress: Second messengers (Ca2+, cGMP and cAMP etc.) play important roles in egress and invasion. We study the triggers, the pathways that transduce these signals and the functional outcome of these highly coordinated processes.

2. Understanding receptor-ligand interactions and the signaling mechanisms mediating parasite invasion: Successful parasite entry into host cells requires a sequence of receptor-ligand interactions, each responsible for a specific step in invasion. We study the signaling mechanisms that regulate the precise spatial and temporal secretion of parasite ligands and how these interactions shape the fate of the invading parasite.

3. Parasite induced modifications of the host cell: We are investigating the molecular mechanisms mediating parasite interaction with the host cell cytoskeleton that facilitates parasite entry without causing damage to the host cell.

4. Malaria vaccine development: We apply our understanding of how proteins function during parasite invasion to identify new vaccine targets and improve the design of existing antigens.

By studying the key factors and the molecular mechanisms by which they regulate host cell egress and invasion, we seek to open new paths for the development of intervention strategies to inhibit invasion and parasite growth.

  • Malaria
  • Parasitology
  • Molecular Microbiology and Immunology
  • Cell biology
  • Host-parasite interactions
  • Vaccine development
  • Small molecule inhibitors of protein-protein interactions

Selected Publications

  • Srinivasan P*, Ekanem E, Diouf A, Tonkin ML, Miura K, Boulanger MJ, Long CA, Narum DL, Miller LH*. Immunization with a functional protein complex required for erythrocyte invasion protects against lethal malaria. Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10311-6. PubMed PMID: 24958881. *Corresponding authors.
  • Srinivasan P*, Yasgar A, Luci DK, Beatty WL, Hu X, Andersen J, Narum DL, Moch JK, Sun H, Haynes JD, Maloney DJ, Jadhav A, Simeonov A, Miller LH. Disrupting malaria parasite AMA1-RON2 interaction with a small molecule prevents erythrocyte invasion. Nat Commun. 2013; PubMed PMID: 23907321. *Corresponding author.
  • Srinivasan P*, Beatty WL, Diouf A, Herrera R, Ambroggio X, Moch JK, Tyler JS, Narum DL, Pierce SK, Boothroyd JC, Haynes JD, Miller LH*. Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion. Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13275-80. PubMed PMID: 21788485. *Corresponding authors.
  • Srinivasan P*, Coppens I, Jacobs-Lorena M. Distinct roles of Plasmodium rhomboid 1 in parasite development and malaria pathogenesis. PLoS Pathog. 2009 Jan;5(1):e1000262. PubMed PMID: 19148267. *Corresponding author.
  • Srinivasan P*, Fujioka H, Jacobs-Lorena M*. PbCap380, a novel oocyst capsule protein, is essential for malaria parasite survival in the mosquito. Cell Microbiol. 2008 Jun;10(6):1304-12. PubMed PMID: 18248630. *Corresponding authors.