Keynote Speaker

Manoj T. Duraisingh, Ph.D.

Professor, Harvard T.H. Chan, School of Public Health

"Elucidating red blood cell determinants of malaria infection"

Biography

Professor Manoj Duraisingh is the John LaPorte Given Professor of Immunology and Infectious Diseases and has been at the Harvard T.H. Chan School of Public Health (Harvard Chan) since 2002. He is also an associate member at the Broad Institute of MIT and Harvard. Professor Duraisingh’s research program at the Harvard Chan focuses on the biology of host-parasite interactions in malaria. His laboratory develops and applies the latest genetic technologies associated with Plasmodium spp. and red blood cells to elucidate and study the critical interactions between the host cell and the malaria parasite. Professor Duraisingh is also engaged in collaborative studies in malaria endemic areas, where he focuses on the biology and pathogenesis of P. vivax and P. falciparum parasites in natural populations. He is lead investigator of the pathogenesis and infection biology project of the India-based National Institutes of Health-funded International Center for Excellence in Malaria Research (ICEMR) in South Asia and investigator of the Malaria Evolution in South Asia (MESA).

Research Description

Malaria remains one of the most serious infectious diseases of humans with an estimated 500 million new infections and approximately 2 million deaths each year. We are interested in understanding the processes that underlie the pathogenesis of human malarial disease at the cellular and molecular level.

Plasmodium falciparum is a protozoan parasite, which multiplies exponentially in red blood cells (erythrocytes) in the course of its life-cycle, resulting in the clinical symptoms associated with severe malaria. We have developed transfection-based molecular and cell biological tools for the functional analysis of genes that may be involved in the initiation and progression of disease. We are also developing forward genetic screens for the identification of new molecules associated with virulence. These advances have coincided with the complete sequencing of the P. falciparum genome, which provides us with a blueprint to unravel the unique biology and genetics of this organism.

In the laboratory, we focus on the molecular basis of erythrocyte invasion by P. falciparum. To initiate a blood-stage infection, invasive forms (known as merozoites) recognize multiple receptors on the surface of the erythrocyte, after which they signal to initiate a cascade of intracellular events to complete the invasion process. We are interested in elucidating the functions of the molecules involved in this complex process. Such an understanding is a prerequisite for the rational design of vaccines directed against this life-cycle stage.

Also of interest is the regulation of antigenic variation in P. falciparum-infected erythrocytes. Following invasion, P. falciparumremodels the infected erythrocyte with the export of various proteins to the erythrocyte surface. Amongst these is a family of molecules, encoded by the var gene family, that are central both to the adherence of infected cells to specific human endothelial receptors and to the evasion of host immune responses raised against this adhesin. We are studying the mechanisms of gene silencing that lead to the mutually exclusive expression of a single member of the var gene family. This includes an understanding of the unique telomere biology of the parasite.

We also have a long-standing interest in elucidating the molecular basis of P. falciparum drug-resistance. In the absence of an effective vaccine, chemotherapy is the mainstay of malaria treatment. This is becomingly increasingly compromised through the development and spread of antimalarial resistance. We are engaged in field projects with collaborators in malaria-endemic areas, including Senegal, Nigeria and Tanzania, to determine the relevance of our laboratory findings in different epidemiological settings.

Download Dr. Duraisingh's Biosketch

Selected Publications

See a full list of Dr. Duraisingh publications.

1. Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition.
   Archer NM, Petersen N, Clark MA, Buckee CO, Childs LM, Duraisingh MT.
   Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7350-7355. doi: 10.1073/pnas.1804388115. Epub 2018 Jun 26.
   PMID: 29946035

2. Epigenetic Variation and Regulation in Malaria Parasites.
   Duraisingh MT, Skillman KM.
   Annu Rev Microbiol. 2018 Sep 8;72:355-375. doi: 10.1146/annurev-micro-090817-062722. Epub 2018 Jun 21.
   PMID: 29927705

3. Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection.
   Obaldia N 3rd, Meibalan E, Sa JM, Ma S, Clark MA, Mejia P, Moraes Barros RR, Otero W, Ferreira MU, Mitchell JR, Milner DA, Huttenhower C, Wirth DF, Duraisingh MT, Wellems TE, Marti M.
   MBio. 2018 May 8;9(3). pii: e00625-18. doi: 10.1128/mBio.00625-18.
   PMID: 29739900

4. Enhanced Ex Vivo Plasmodium vivax Intraerythrocytic Enrichment and Maturation for Rapid and Sensitive Parasite Growth Assays.
   Rangel GW, Clark MA, Kanjee U, Lim C, Shaw-Saliba K, Menezes MJ, Mascarenhas A, Chery L, Gomes E, Rathod PK, Ferreira MU, Duraisingh MT.
   Antimicrob Agents Chemother. 2018 Mar 27;62(4). pii: e02519-17. doi: 10.1128/AAC.02519-17. Print 2018 Apr.
   PMID: 29378713

Southern California Eukaryotic Pathogen Symposium — Nov. 28, 2018

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