ABOUT THE RESEARCHER

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.

 

BACKGROUND

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. 

Selected Publications

  1. 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
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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. ?d T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis. Nat Immunol. 2021 Jan 11. View abstract
  2. Depletion of the mini-chromosome maintenance complex binding protein allows the progression of cytokinesis despite abnormal karyokinesis during the asexual development of Plasmodium falciparum. Cell Microbiol. 2021 Mar; 23(3):e13284. View abstract
  3. Ultrasensitive CRISPR-based diagnostic for field-applicable detection of Plasmodium species in symptomatic and asymptomatic malaria. Proc Natl Acad Sci U S A. 2020 10 13; 117(41):25722-25731. View abstract
  4. Three-dimensional ultrastructure of Plasmodium falciparum throughout cytokinesis. PLoS Pathog. 2020 06; 16(6):e1008587. View abstract
  5. Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria. Nature. 2020 06; 582(7810):104-108. View abstract
  6. A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites. J Infect Dis. 2020 03 02; 221(6):956-962. View abstract
  7. Influence of Plasmodium falciparum Calcium-Dependent Protein Kinase 5 (PfCDPK5) on the Late Schizont Stage Phosphoproteome. mSphere. 2020 01 08; 5(1). View abstract
  8. An essential contractile ring protein controls cell division in Plasmodium falciparum. Nat Commun. 2019 05 16; 10(1):2181. View abstract
  9. Calcium-Dependent Protein Kinase 5 Is Required for Release of Egress-Specific Organelles in Plasmodium falciparum. mBio. 2018 02 27; 9(1). View abstract
  10. Getting Your Head around Cerebral Malaria. . 2017 11 08; 22(5):586-588. View abstract
  11. Functional Analysis Reveals Geographical Variation in Inhibitory Immune Responses Against a Polymorphic Malaria Antigen. J Infect Dis. 2017 07 15; 216(2):267-275. View abstract
  12. PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum. Nat Commun. 2017 07 05; 8(1):63. View abstract
  13. The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum. mBio. 2017 06 13; 8(3). View abstract
  14. Erratum: Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony. Nat Microbiol. 2017 Mar 06; 2:17038. View abstract
  15. Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony. Nat Microbiol. 2017 Feb 17; 2:17017. View abstract
  16. Receptor for Activated C-Kinase 1 (PfRACK1) is required for Plasmodium falciparum intra-erythrocytic proliferation. Mol Biochem Parasitol. 2017 01; 211:62-66. View abstract
  17. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites. Nat Commun. 2016 04 28; 7:11449. View abstract
  18. Dynamical features of the Plasmodium falciparum ribosome during translation. Nucleic Acids Res. 2015 Dec 02; 43(21):10515-24. View abstract
  19. Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection. Science. 2014 May 23; 344(6186):871-7. View abstract
  20. Inside scoop on outside proteins. Infect Immun. 2014 Mar; 82(3):921-3. View abstract
  21. A DOC2 protein identified by mutational profiling is essential for apicomplexan parasite exocytosis. Science. 2012 Jan 13; 335(6065):218-21. View abstract
  22. Identification and validation of tetracyclic benzothiazepines as Plasmodium falciparum cytochrome bc1 inhibitors. Chem Biol. 2011 Dec 23; 18(12):1602-10. View abstract
  23. A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science. 2010 May 14; 328(5980):910-2. View abstract
  24. 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. View abstract
  25. Suggestive evidence for Darwinian Selection against asparagine-linked glycans of Plasmodium falciparum and Toxoplasma gondii. Eukaryot Cell. 2010 Feb; 9(2):228-41. View abstract
  26. Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors. Bioorg Med Chem Lett. 2009 Feb 01; 19(3):972-5. View abstract
  27. Identification and characterization of small molecule inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J Biol Chem. 2008 Dec 12; 283(50):35078-85. View abstract
  28. Emergence of community-associated methicillin resistant Staphylococcus aureus in Hawaii, 2001-2003. J Infect. 2007 Apr; 54(4):349-57. View abstract
  29. Intracellular trafficking of HIV-1 cores: journey to the center of the cell. Curr Top Microbiol Immunol. 2003; 281:179-208. View abstract
  30. 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. View abstract
  31. HIV-1 infection requires a functional integrase NLS. Mol Cell. 2001 May; 7(5):1025-35. View abstract
  32. 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. View abstract