Apicomplexan Molecular Physiology Section
Sanjay Desai, M.D., Ph.D.
Chief, Apicomplexan Molecular Physiology Section
Contact: For contact information, search the NIH Enterprise Directory.
Specialty(s): Infectious Disease, Internal Medicine
Major Areas of Research
- Cellular and molecular biology of the malaria parasite
- Identification and characterization of parasite-specific ion channels required for pathogen survival in humans and their mosquito vectors
- Molecular, structural, and biochemical studies of the plasmodial surface anion channel (PSAC) at the host membrane of infected erythrocytes
- Discovery and development of transport inhibitors as future antimalarial drugs
Program Description
We are interested in how malaria parasites acquire nutrients and other essential solutes from their human and vector hosts. Our studies have identified several unusual ion channels that play a central role in pathogen development. One of these channels, the plasmodial surface anion channel (PSAC), is exposed on the infected erythrocyte surface in bloodstream infections and is a recognized drug target.
Significant accomplishments include the following:
- Discovered the plasmodial surface anion channel (PSAC) with patch-clamp studies of human erythrocytes
- Identified PSAC’s molecular determinants, physiological role, contribution to a novel drug resistance mechanism, and potent inhibitors as advanced antimalarial drug leads
- Discovered and characterized a large-conductance ion channel on the parasitophorous vacuolar membrane (PVM) surrounding the intracellular parasite
- Implicated distinct parasite genetic elements in increased Ca++ permeability of infected erythrocytes
Inquiries about predoctoral and postdoctoral fellowships, as well as Ph.D. studentships in the NIH Graduate Partnership Program, are welcome. Contact Dr. Desai via email at sdesai@niaid.nih.gov.
Biography
Education
M.D., Ph.D., Washington University in St. Louis
Dr. Desai received his M.D. and Ph.D. from Washington University in St. Louis. Following an internal medicine residency and infectious diseases fellowship at Duke University Medical Center, he joined the Division of Intramural Research. His work focuses on the molecular and cellular biology of malaria parasites.
Selected Publications
Schureck MA, Darling JE, Merk A, Shao J, Daggupati G, Srinivasan P, Olinares PDB, Rout MP, Chait BT, Wollenberg K, Subramaniam S, Desai SA. Malaria parasites use a soluble RhopH complex for erythrocyte invasion and an integral form for nutrient uptake. Elife. 2021 Jan 4; 10:e65282.
Gupta A, Bokhari AAB, Pillai AD, Crater AK, Gezelle J, Saggu G, Nasamu AS, Ganesan SM, Niles JC, Desai SA. Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodium falciparum genetic cross. PLoS Pathog. 2020 Feb 18; 16(2):e1008363.
Ito D, Schureck MA, Desai SA. An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites. Elife. 2017 Feb 21; 6:e23485.
Nguitragool W, Bokhari AA, Pillai AD, Rayavara K, Sharma P, Turpin B, Aravind L, Desai SA. Malaria parasite clag3 genes determine channel-mediated nutrient uptake by infected red blood cells. Cell. 2011 May 27;145(5):665-77.
Pillai AD, Pain M, Solomon T, Bokhari AA, Desai SA. A cell-based high-throughput screen validates the plasmodial surface anion channel as an antimalarial target. Mol Pharmacol. 2010 May;77(5):724-33.
Desai SA, Bezrukov S, Zimmerberg J. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature. 2000 Aug 31;406(6799):1001-5.
Inventions & Patents
S.L. Waidyarachchi, S.L. Nguyen, X. Ding, S. Adhikari, J.D. Williams, N.P. Peet, Z.D. Aron, S.A. Desai and M.M. Butler, inventors. Compounds and Methods for treating Malaria. PCT patent PCT/US2022/013223. 2022 Jan 21.
T. Sawetzki, D. Marr, C. Eggleton, and S.A. Desai, inventors. Dynamic Viscoelasticity as a Rapid Single-Cell Biomarker. PCT application in process. 2013.
S.A. Desai, inventor. Plasmodial surface anion channel inhibitors for the treatment of malaria. HHS reference E-145-2011-0-US-01. 2011 Apr 12.
Desai SA, Pillai AD, inventors; Government of the United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Inhibitors of the plasmodial surface anion channel as antimalarials. PCT patent PCT/US09/50637. 2009 Jul 15.
Research Group
The Apicomplexan Molecular Physiology Section (AMPS) studies the cell and molecular biology of malaria parasites. We are focused on ion channels and transporters unique to these parasites and aim to develop novel antimalarial therapies against these targets.
