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Jatin Mahesh Vyas, M.D., PH.D.

TitleAssistant Professor of Medicine
InstitutionMassachusetts General Hospital
DepartmentMedicine
AddressMassachusetts General Hospital
Infectious Disease, GRJ 504
55 Fruit St
Boston MA 02114
Phone617/643-6444
Fax617/643-6443

 Overview 
 overview
My research interests focus on the immune responses to fungal pathogens. Charged with the responsibility to protect a host from pathogenic microorganisms, the immune system detects, neutralizes, and eliminates these invaders using many different specialized cells. One arm of the immune system deploys sentinels throughout the body. Their purpose is two-fold. First, professional antigen presenting cells (APCs) capture invading pathogens by phagocytosis and degrade them before they cause additional harm to the host. Second, APCs must “deliver the message” about the presence of pathogens in the periphery to T cells located in regional lymph nodes in order to amplify the immune response. How does an APC talk to the T cell? Both cells come together and form a cell-cell synapse whereby the T cell interrogates the surface of the APC for the presence of a pathogen-specific signal that, when present, activates the T cell. Specialized immune proteins, termed class II MHC molecules, are heterodimeric protein complexes that present this signal. Dendritic cells (DCs) are potent professional APCs that express abundant class II MHC molecules and possess the unique capacity to activate naïve T cells. In order to serve as an effective APC, newly-captured pathogens must be shuttled to the endolysosomes for degradation. To accomplish this task, APCs place pathogens into membrane-delimited compartments termed phagosomes. These compartments undergo a series of membrane modifications, drop their pH and activate proteases which facilitate degradation of the cargo. The biomolecular mechanism of phagosome maturation is incompletely understood including the identity and kinetics of association and dissociation of most proteins on phagosomal membranes. When properly folded, class II MHC molecules form a pocket for pathogen-derived peptides (protein fragments). In the endolysosome, a specialized compartment within the APC, class II MHC molecules associate with pathogen-derived peptides and traffic from intracellular compartments to the cell surface. Antigen presentation requires the coordinated efforts of multiple host proteins including members of the tetraspanin superfamily, though their exact function in this process remains poorly understood.
When the process of antigen processing and presentation works well, the host is protected from a number of virulent microorganisms. Failure of an effective immune response, however, can lead to overwhelming infection and possibly death. This failure is caused typically by specific cellular defects in the immune system as seen in HIV infection, older age, or administration of immunosuppressive medications. My major goal is to understand the rules that govern the fate of fungal pathogens including Cryptococcus neoformans and Candida albicans upon phagocytosis by real-time visualization of professional APCs expressing fluorescently-tagged proteins relevant to antigen processing and presentation using spinning-disk confocal microscopy.
In the remaining 15% of my time, I serve as an Infectious Disease visit at the Massachusetts General Hospital and Medical Visit for the Department of Medicine. I use this time to expose trainees to fundamental principles in science and how they impact clinical medicine today.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Vyas JM, González RG, Pierce VM. Case records of the Massachusetts General Hospital. Case 15-2013. A 76-year-old man with fever, worsening renal function, and altered mental status. N Engl J Med. 2013 May 16; 368(20):1919-27.
    View in: PubMed
  2. Mansour MK, Tam JM, Khan NS, Seward M, Davids PJ, Puranam S, Sokolovska A, Sykes DB, Dagher Z, Becker C, Tanne A, Reedy JL, Stuart LM, Vyas JM. Dectin-1 Activation Controls Maturation of ß-1,3-Glucan-containing Phagosomes. J Biol Chem. 2013 May 31; 288(22):16043-54.
    View in: PubMed
  3. Grimm MJ, Vethanayagam RR, Almyroudis NG, Dennis CG, Khan AN, D'Auria AC, Singel KL, Davidson BA, Knight PR, Blackwell TS, Hohl TM, Mansour MK, Vyas JM, Röhm M, Urban CF, Kelkka T, Holmdahl R, Segal BH. Monocyte- and macrophage-targeted NADPH oxidase mediates antifungal host defense and regulation of acute inflammation in mice. J Immunol. 2013 Apr 15; 190(8):4175-84.
    View in: PubMed
  4. Huett A, Heath RJ, Begun J, Sassi SO, Baxt LA, Vyas JM, Goldberg MB, Xavier RJ. The LRR and RING Domain Protein LRSAM1 Is an E3 Ligase Crucial for Ubiquitin-Dependent Autophagy of Intracellular Salmonella Typhimurium. Cell Host Microbe. 2012 Dec 13; 12(6):778-90.
    View in: PubMed
  5. Mansour MK, Tam JM, Vyas JM. The cell biology of the innate immune response to Aspergillus fumigatus. Ann N Y Acad Sci. 2012 Dec; 1273(1):78-84.
    View in: PubMed
  6. Vyas JM. Insights into dendritic cell function using advanced imaging modalities. Virulence. 2012 Nov 15; 3(7):690-4.
    View in: PubMed
  7. Vyas JM. The dendritic cell: The general of the army. Virulence. 2012 Nov 15; 3(7):601-2.
    View in: PubMed
  8. Vyas JM, Marasco WA. Fatal fulminant hepatic failure from adenovirus in allogeneic bone marrow transplant patients. Case Rep Infect Dis. 2012; 2012:463569.
    View in: PubMed
  9. Tam JM, Mansour MK, Khan NS, Yoder NC, Vyas JM. Use of fungal derived polysaccharide-conjugated particles to probe Dectin-1 responses in innate immunity. Integr Biol (Camb). 2012 Feb; 4(2):220-7.
    View in: PubMed
  10. Coleman JJ, Muhammed M, Kasperkovitz PV, Vyas JM, Mylonakis E. Fusarium pathogenesis investigated using Galleria mellonella as a heterologous host. Fungal Biol. 2011 Dec; 115(12):1279-89.
    View in: PubMed
  11. Mansour MK, Vyas JM, Levitz SM. Dynamic virulence: real-time assessment of intracellular pathogenesis links Cryptococcus neoformans phenotype with clinical outcome. MBio. 2011; 2(5).
    View in: PubMed
  12. Kasperkovitz PV, Khan NS, Tam JM, Mansour MK, Davids PJ, Vyas JM. Toll-like receptor 9 modulates macrophage antifungal effector function during innate recognition of Candida albicans and Saccharomyces cerevisiae. Infect Immun. 2011 Dec; 79(12):4858-67.
    View in: PubMed
  13. Tam JM, Castro CE, Heath RJ, Mansour MK, Cardenas ML, Xavier RJ, Lang MJ, Vyas JM. Use of an optical trap for study of host-pathogen interactions for dynamic live cell imaging. J Vis Exp. 2011; (53).
    View in: PubMed
  14. Vyas JM. The duality of Aspergillus terreus: Differential immune responses to distinct conidia. Virulence. 2011 May-Jun; 2(3):181-4.
    View in: PubMed
  15. Tam JM, Castro CE, Heath RJ, Cardenas ML, Xavier RJ, Lang MJ, Vyas JM. Control and manipulation of pathogens with an optical trap for live cell imaging of intercellular interactions. PLoS One. 2010; 5(12):e15215.
    View in: PubMed
  16. Xia Y, Cortez-Retamozo V, Niederkofler V, Salie R, Chen S, Samad TA, Hong CC, Arber S, Vyas JM, Weissleder R, Pittet MJ, Lin HY. Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages. J Immunol. 2011 Feb 1; 186(3):1369-76.
    View in: PubMed
  17. Artavanis-Tsakonas K, Kasperkovitz PV, Papa E, Cardenas ML, Khan NS, Van der Veen AG, Ploegh HL, Vyas JM. The tetraspanin CD82 is specifically recruited to fungal and bacterial phagosomes prior to acidification. Infect Immun. 2011 Mar; 79(3):1098-106.
    View in: PubMed
  18. Kasperkovitz PV, Cardenas ML, Vyas JM. TLR9 is actively recruited to Aspergillus fumigatus phagosomes and requires the N-terminal proteolytic cleavage domain for proper intracellular trafficking. J Immunol. 2010 Dec 15; 185(12):7614-22.
    View in: PubMed
  19. Bender Ignacio RA, Liu AY, Sohani AR, Vyas JM. Hodgkin's lymphoma masquerading as vertebral osteomyelitis in a man with diabetes: a case report. J Med Case Rep. 2010; 4:102.
    View in: PubMed
  20. Vyas JM, Van der Veen AG, Ploegh HL. The known unknowns of antigen processing and presentation. Nat Rev Immunol. 2008 Aug; 8(8):607-18.
    View in: PubMed
  21. Vyas JM, Telford SR, Robbins GK. Treatment of refractory Babesia microti infection with atovaquone-proguanil in an HIV-infected patient: case report. Clin Infect Dis. 2007 Dec 15; 45(12):1588-90.
    View in: PubMed
  22. Vyas JM, Telford III S, Robbins GK. Treatment of Refractory Babesia microti Infection with Atovaquone-Proguanil in an HIV-Infected Patient: Case Report. Clinical Infectious Disease. 2007; 45:1588-1590.
  23. Vyas JM, Kim YM, Artavanis-Tsakonas K, Love JC, Van der Veen AG, Ploegh HL. Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells. J Immunol. 2007 Jun 1; 178(11):7199-210.
    View in: PubMed
  24. Vyas JM, Kasmar A, Holden J, Chang H, Hohmann E. Abdominal Actinomycosis after Laparascopic Cholecystectomy: Case Reports and Review. Clinical Infectious Diseases. 2007; 44:e1-e4.
  25. Vyas JM, Kasmar A, Chang HR, Holden J, Hohmann E. Abdominal abscesses due to actinomycosis after laparoscopic cholecystectomy: case reports and review. Clin Infect Dis. 2007 Jan 15; 44(2):e1-4.
    View in: PubMed
  26. Trivedi V, Zhang SC, Castoreno AB, Stockinger W, Shieh EC, Vyas JM, Frickel EM, Nohturfft A. Immunoglobulin G signaling activates lysosome/phagosome docking. Proc Natl Acad Sci U S A. 2006 Nov 28; 103(48):18226-31.
    View in: PubMed
  27. Artavanis-Tsakonas K, Love JC, Ploegh HL, Vyas JM. Recruitment of CD63 to Cryptococcus neoformans phagosomes requires acidification. Proc Natl Acad Sci U S A. 2006 Oct 24; 103(43):15945-50.
    View in: PubMed
  28. Wozniak KL, Vyas JM, Levitz SM. In vivo role of dendritic cells in a murine model of pulmonary cryptococcosis. Infect Immun. 2006 Jul; 74(7):3817-24.
    View in: PubMed
  29. Gewurz B, Vyas JM, and Ploegh H.L. Subversion of adaptive immunity: immune evasion of T cells. Human Herpesviruses: Biology, Therapy and Immunoprophylaxis. Editor: Ann M. Arvin, MD. 2006.
  30. Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, Vyas JM, Boes M, Ploegh HL, Fox JG, Littman DR, Reinecker HC. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science. 2005 Jan 14; 307(5707):254-8.
    View in: PubMed
  31. Fiebiger E, Hirsch C, Vyas JM, Gordon E, Ploegh HL, Tortorella D. Dissection of the dislocation pathway for type I membrane proteins with a new small molecule inhibitor, eeyarestatin. Mol Biol Cell. 2004 Apr; 15(4):1635-46.
    View in: PubMed
  32. Vyas JM, Marasco, WA. Fatal fulminant hepatic failure from adenovirus in allogenic bone marrow transplant patients. Infectious Disease Society of America. 2003.
  33. Jatin M Vyas, MD, PhD Mary Jane Ferraro, PhD, MPH. Antibiotic susceptibility testing in specific clinical situations. 2003.
  34. Jatin M Vyas, MD, PhD Mary Jane Ferraro, PhD, MPH. Overview of antibacterial susceptibility testing. 2003.
  35. Dow SW, Roberts A, Vyas J, Rodgers J, Rich RR, Orme I, Potter TA. Immunization with f-Met peptides induces immune reactivity against Mycobacterium tuberculosis. Tuber Lung Dis. 2000; 80(1):5-13.
    View in: PubMed
  36. Vyas JM, Rodgers JR, Rich RR. H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding. J Exp Med. 1995 May 1; 181(5):1817-25.
    View in: PubMed
  37. Vyas JM, Lamphear JL and Rich RR. The language of immunology. Clinical Immunology: Principles and Practice. Editor: Robert R. Rich. 1995; G1-8.
  38. Vyas JM. The peptide binding specificity of the MHC class I-b molecule, H-2M3a. 1994.
  39. Shawar SM, Vyas JM, Rodgers JR, Rich RR. Antigen presentation by major histocompatibility complex class I-B molecules. Annu Rev Immunol. 1994; 12:839-80.
    View in: PubMed
  40. Vyas JM, Rich RR, Howell DD, Shawar SM, Rodgers JR. Availability of endogenous peptides limits expression of an M3a-Ld major histocompatibility complex class I chimera. J Exp Med. 1994 Jan 1; 179(1):155-65.
    View in: PubMed
  41. Shawar SM, Vyas JM, Shen E, Rodgers JR, Rich RR. Differential amino-terminal anchors for peptide binding to H-2M3a or H-2Kb and H-2Db. J Immunol. 1993 Jul 1; 151(1):201-10.
    View in: PubMed
  42. Vyas JM, Shawar SM, Rodgers JR, Cook RG, Rich RR. Biochemical specificity of H-2M3a. Stereospecificity and space-filling requirements at position 1 maintain N-formyl peptide binding. J Immunol. 1992 Dec 1; 149(11):3605-11.
    View in: PubMed
  43. Shawar SM, Vyas JM, Rodgers JR, Cook RG, Rich RR. Specialized functions of major histocompatibility complex class I molecules. II. Hmt binds N-formylated peptides of mitochondrial and prokaryotic origin. J Exp Med. 1991 Oct 1; 174(4):941-4.
    View in: PubMed
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