BBS Faculty Member - Jeffrey Dvorin

Jeffrey Dvorin

Department of Pediatrics

Boston Children's Hospital
Enders Building, Room 878.2
300 Longwood Avenue
Boston, MA 02115
Tel: 617-919-2900
Fax: 617-730-0254
Email: Jeffrey.Dvorin@childrens.harvard.edu
Visit my lab page here.



The Dvorin Laboratory is part of the Division of Infectious Diseases at Boston Children’s Hospital, the primary pediatric teaching hospital of Harvard Medical School. The research in our laboratory investigates the molecular pathogenesis of infection by the parasites that cause human malaria. We primarily study the replication of Plasmodium falciparum in human red blood cells.

The major goal of our lab is to identify fundamental biological processes within the parasite life cycle. One of these fundamental processes is the regulated and efficient egress of the parasite out of the human red blood cells that occurs during asexual replication. The parasite relies on egress for a sequential round of invasion; this allows exponential expansion of the parasite during the blood-stage of malaria. Parasite egress requires a calcium-mediated signal, but the proteins that mediate the critical calcium-dependent steps of parasite egress have not been fully identified or characterized. Using genetic, cell biological, and novel molecular biology techniques, we are interested in multiple aspects of parasite egress from an infected human erythrocyte.

Role of PfCDPK5 in parasite egress
PfCDPK5 is a calcium-dependent protein kinase that has recently been shown to be essential for parasite replication. Parasites with a knockdown of PfCDPK5 expression are blocked at a very late stage of their development, just prior to egress out of the human red blood cell. Current projects in the laboratory are focused on the specific molecular mechanism of PfCDPK5 function and the PfCDPK5-mediated block in replication.

Calcium-dependent processes in parasite replication
A second major focus of the laboratory is to characterize the function of multiple additional calcium-responsive signaling pathways within the development and replication of the parasite. Utilizing state-of-the-art molecular techniques, we are investigating the roles of several novel proteins that may have a role in the calcium-signaling pathways.

Discovery of novel and essential parasite genes
The third major focus of the laboratory is the discovery and molecular characterization of novel and essential genes that are required for the asexual replication of P. falciparum. Using both reverse and forward genetic techniques, we aim to elucidate the function of several parasite genes currently annotated as "hypothetical" and "conserved".



Last Update: 2/15/2017



Publications

For a complete listing of publications click here.

 


 

Dvorin JD, Bei AK, Coleman BI, Duraisingh MT. Functional Diversification between Two Related Plasmodium falciparum Merozoite Invasion Ligands is Determined by Changes in the Cytoplasmic Domain. Molecular Microbiology 2010; 75(4) 990-1006.

Dvorin JD, Martyn DC, Patel SD, Grimley JS, Collins CR, Hopp CS, Bright AT, Westenberger S, Winzeler E, Blackman MJ, Baker DA, Wandless TJ, Duraisingh MT. A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science 2010; 328(5980): 910-912. PMCID: PMC3109083.

Farrell A*, Thirugnanam S*, Lorestani A*,
Dvorin JD*, Eidell KP, Ferguson DJP, Anderson-White BR, Duraisingh MT, Marth GT, Gubbels M-J. A DOC2 Protein Identified by Mutational Profiling is Essential for Apicomplexan Parasite Exocytosis. Science, 2012; 335(6065): 218-21. PMCID: PMC3354045.
* Co-first authors

Dvorin JD. The Inside Scoop on Outside Proteins. Infection and Immunity, 2014; 82: 921-923.

Raj DK, Nixon CP, Nixon CE,
Dvorin JD, DiPetrillo CG, Pond-Tor S, Wu H, Jolly G, Pischel L, Lu A, Michelow IC, Cheng L, Conteh S, McDonald EA, Absalon S, Holte SE, Friedman JF, Fried M, Duffy PE, Kurtis JD. Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection. Science 2014; 344(6186): 871-77.



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