Major Areas of Research
- Cellular and molecular biology of the malaria parasite
- Unusual parasite ion channels, e.g., the plasmodial surface anion channel (PSAC), required for parasite survival within human erythrocytes
- Identification of PSAC’s gene(s) with molecular, genetic, and biochemical approaches
- Characterization of PSAC’s unusual functional properties with the goal of understanding both structure and physiological role
- Identification of novel, high-affinity PSAC antagonists that may be starting points for the development of new antimalarial drugs
We are interested in how malaria parasites acquire nutrients and other essential solutes from the human bloodstream. Our studies have identified two unusual ion channels that play a central role in trafficking solutes between serum and parasite compartments. One of these channels, the plasmodial surface anion channel (PSAC), is exposed on the infected erythrocyte surface and is generally recognized as an important drug target.
Significant accomplishments include the following:
- Determination that PSAC is the primary uptake mechanism for diverse organic and inorganic solutes
- Discovery of a novel drug resistance mechanism in malaria parasites involving reduced PSAC-mediated uptake
- Use of high-throughput screening to identify novel, high-affinity PSAC inhibitors suitable for antimalarial drug development
- Identification of the clag3 genes as determinants of PSAC activity
Our work was highlighted with the first animated cover of a major biological sciences journal. The animation is accessible from the print journal using a smart phone with a downloaded QR code reader. Click the journal cover image below to view the 3-D animation on YouTube.
Cover of Cell volume 145, number 5. The pictured QR code links to an online 3-D animation of circulating human erythrocytes with two cells infected by malaria parasites. Intracellular parasites acquire nutrients via PSAC on the host membrane. Animation by Anita Mora and Austin Athman (RML, NIAID).
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 email@example.com.
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.
Current Group Members
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.
Hill DA, Pillai AD, Nawaz F, Hayton K, Doan L, Lisk G, Desai SA. A blasticidin S-resistant Plasmodium falciparum mutant with a defective plasmodial surface anion channel. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):1063-8.
Alkhalil A, Cohn JV, Wagner MA, Cabrera JS, Rajapandi T, Desai SA. Plasmodium falciparum likely encodes the principal anion channel on infected human erythrocytes. Blood. 2004 Dec 15;104(13):4279-86.
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.
Plasmodial surface anion channel inhibitors for the treatment of malaria. HHS reference E-145-2011-0-US-01.
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.