Research

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Jeffrey  Dvorin, MD, PhD

Jeffrey Dvorin MD
Department:
Medicine Research
Division
Infectious Diseases Research
Hospital Title:
Associate in Medicine
Academic Title:
Assistant Professor of Pediatrics, Harvard Medical School
Research Focus Area:
MalariaParasitologyTropical Medicine
Contact Via Email
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Research Overview

 Dr. Dvorin’s research focuses on the molecular pathogenesis of the human malaria parasite Plasmodium falciparum.  The major goal of the Dvorin lab is to identify fundamental biological processes within the parasite life cycle.  One of these fundamental processes is the regulated and efficient egress from human erythrocytes 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, the Dvorin lab is interested in multiple aspects of parasite egress from an infected human erythrocyte.

About Jeffrey Dvorin

Dr. Jeffrey Dvorin received his undergraduate degree in Physics from Brown University.  He then attended the University of Pennsylvania School of Medicine to pursue a combined M.D./Ph.D. in the Medical Scientist Training Program.  During his graduate work, he studied the mechanisms of nuclear entry for the human immunodeficiency virus in the laboratory of Michael Malim.  He completed his pediatric residency at the Children’s Hospital of Philadelphia and then moved to the Children’s Hospital Boston for his fellowship in Pediatric Infectious Diseases.  After finishing his clinical fellowship year in June 2007, he joined the laboratory of Dr. Manoj Duraisingh in the Department of Immunology and Infectious Diseases at the Harvard School of Public Health to study the molecular pathogenesis of the human malaria parasite Plasmodium falciparum.  His research focused on developing novel genetic techniques to understand P. falciparum growth and replication with the ultimate goal of identifying new therapies for malaria.  In Dr. Duraisingh’s laboratory, Dr. Dvorin identified an essential kinase for P. falciparum replication PfCDPK5 that is potentially an ideal target for rational design of anti-malarial medications. 

Key Publications

  • 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
  • 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.
  • Dong C, Patel V, Yang JC, Dvorin JD, Duraisingh MT, Clardy J, Wirth DF. Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors. Bioorganic & Medicinal Chemistry Letters 2009; 19: 972-975.
  • Patel V, Booker M, Kramer M, Ross L, Celatka CA, Kennedy LM, Dvorin JD, Duraisingh MT, Sliz P, Wirth DF, Clardy J. Identification and characterization of small molecule inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. Journal of Biological Chemistry 2008; 283(50): 35078-35085.
  • Estivariz CF, Park SY, Hageman JC, Dvorin JD, Melish MM, Arpon R, Coon P, Slavish S, Kim M, McDougal LK, Jensen B, McAllister S, Lonsway D, Killgore G, Effler PE, Jernigan DB. Emergence of community-associated methicillin resistant Staphylococcus aureus in Hawaii, 2001-2003. Journal of Infection 2007; 54: 349-357.
  • Dvorin JD, Bell P, Maul GG, Yamashita M, Emerman M, Malim MH.  Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. Journal of Virology 2002; 76(23): 12087-12096.
  • Bouyac-Bertoia M*, Dvorin JD*, Fouchier RAM, Jenkins J, Meyer BE, Wu LI, Emerman M, Malim MH. HIV-1 infection requires a functional integrase NLS. Molecular Cell 2001; 7: 1025-1035.

* Co-first authors

Publications

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  1. Blomqvist K, DiPetrillo C, Streva VA, Pine S, Dvorin JD. Receptor for Activated C-Kinase 1 (PfRACK1) is required for Plasmodium falciparum intra-erythrocytic proliferation. Mol Biochem Parasitol. 2016 Oct 11.
  2. Absalon S, Robbins JA, Dvorin JD. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites. Nat Commun. 2016 Apr 28; 7:11449.
  3. Sun M, Li W, Blomqvist K, Das S, Hashem Y, Dvorin JD, Frank J. Dynamical features of the Plasmodium falciparum ribosome during translation. Nucleic Acids Res. 2015 Dec 2; 43(21):10515-24.
  4. Raj DK, Nixon CP, Nixon CE, Dvorin JD, DiPetrillo CG, Pond-Tor S, Wu HW, 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 May 23; 344(6186):871-7.
  5. Dvorin JD. Inside scoop on outside proteins. Infect Immun. 2014 Mar; 82(3):921-3.
  6. Farrell A, Thirugnanam S, Lorestani A, Dvorin JD, Eidell KP, Ferguson DJ, Anderson-White BR, Duraisingh MT, Marth GT, Gubbels MJ. A DOC2 protein identified by mutational profiling is essential for apicomplexan parasite exocytosis. Science. 2012 Jan 13; 335(6065):218-21.
  7. Dong CK, Urgaonkar S, Cortese JF, Gamo FJ, Garcia-Bustos JF, Lafuente MJ, Patel V, Ross L, Coleman BI, Derbyshire ER, Clish CB, Serrano AE, Cromwell M, Barker RH, Dvorin JD, Duraisingh MT, Wirth DF, Clardy J, Mazitschek R. Identification and validation of tetracyclic benzothiazepines as Plasmodium falciparum cytochrome bc1 inhibitors. Chem Biol. 2011 Dec 23; 18(12):1602-10.
  8. 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. Mol Microbiol. 2010 Feb; 75(4):990-1006.
  9. Bushkin GG, Ratner DM, Cui J, Banerjee S, Duraisingh MT, Jennings CV, Dvorin JD, Gubbels MJ, Robertson SD, Steffen M, O'Keefe BR, Robbins PW, Samuelson J. Suggestive evidence for Darwinian Selection against asparagine-linked glycans of Plasmodium falciparum and Toxoplasma gondii. Eukaryot Cell. 2010 Feb; 9(2):228-41.
  10. Dong CK, Patel V, Yang JC, Dvorin JD, Duraisingh MT, Clardy J, Wirth DF. Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors. Bioorg Med Chem Lett. 2009 Feb 1; 19(3):972-5.
  11. Show all
  12. Patel V, Booker M, Kramer M, Ross L, Celatka CA, Kennedy LM, Dvorin JD, Duraisingh MT, Sliz P, Wirth DF, Clardy J. Identification and characterization of small molecule inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J Biol Chem. 2008 Dec 12; 283(50):35078-85.
  13. Estivariz CF, Park SY, Hageman JC, Dvorin J, Melish MM, Arpon R, Coon P, Slavish S, Kim M, McDougal LK, Jensen B, McAllister S, Lonsway D, Killgore G, Effler PE, Jernigan DB. Emergence of community-associated methicillin resistant Staphylococcus aureus in Hawaii, 2001-2003. J Infect. 2007 Apr; 54(4):349-57.
  14. Dvorin JD, Malim MH. Intracellular trafficking of HIV-1 cores: journey to the center of the cell. Curr Top Microbiol Immunol. 2003; 281:179-208.
  15. Dvorin JD, Bell P, Maul GG, Yamashita M, Emerman M, Malim MH. Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. J Virol. 2002 Dec; 76(23):12087-96.
  16. Bouyac-Bertoia M, Dvorin JD, Fouchier RA, Jenkins Y, Meyer BE, Wu LI, Emerman M, Malim MH. HIV-1 infection requires a functional integrase NLS. Mol Cell. 2001 May; 7(5):1025-35.
  17. Fultz PN, Vance PJ, Endres MJ, Tao B, Dvorin JD, Davis IC, Lifson JD, Montefiori DC, Marsh M, Malim MH, Hoxie JA. In vivo attenuation of simian immunodeficiency virus by disruption of a tyrosine-dependent sorting signal in the envelope glycoprotein cytoplasmic tail. J Virol. 2001 Jan; 75(1):278-91.
  18. 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 May 14; 328(5980):910-2.
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