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William Marshall

TitleAssociate Professor
InstitutionUMass Chan Medical School
AddressUMass Chan Medical School
364 Plantation Street LRB
Worcester MA 01605
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DivisionInfectious Diseases And Immunology

    Collapse Biography 
    Collapse education and training
    Harvard University, Cambridge, MA, United StatesABBiology
    Columbia University, New York, NY, United StatesMD

    Collapse Overview 
    Collapse overview

    Academic Background


    • A.B., Harvard University, 1982
    • M.D., Columbia University, 1986

    Post-Graduate Training:

    • Internal Medicine Residency, Columbia-Presbyterian Medical Center, New York, NY, 1986-89
    • Infectious Disease Fellowship, Beth-Israel Hospital, Brigham & Women's Hospital, and Dana-Farber Cancer Institute, Boston, MA, 1989-92

    Board Certification:

    • National Board of Medical Examiners, 1987
    • Diplomate, American Board of Internal Medicine, 1989
    • Diplomate, American Board of Internal Medicine (Infectious Diseases), 1992, 2002

    Honors and Awards:

    • Leukemia & Lymphoma Society of America, Translational Research Award
    • Physician Scientist Award
    • Michael Aranow Award, College of Physicians and Surgeons
    • Cum Laude, Biology, Harvard University, Cambridge, MA

    Photo of Dr William L MarshallResearch Interests

    My research interests are in the mechanisms that viruses employ to evade innate immunity, including cell-mediated death pathways that ordinarily regulate viral replication. Specifically, my laboratory is studying:

    1. the function of novel viral bcl-2s in the EBV and poxvirus life-cycles,
    2. TNF family members’ effects upon viral replication, and
    3. mechanisms of viral evasion of the innate immune response.

    Poxvirus Inhibitin of Innate Immune Signaling

    WLMarshall, MD

    • Toll like receptors (TLRs) are receptors for molecular patterns of microbial pathogens. TLRs signal to transcription factors such as NF-kB & IRF3, inducing antiviral cytokines and interferons.
    • N1L is a vaccinia virus gene responsible for a 10,000 fold increase in virulence (Kotwal, 1989), inhibition of NF-kB and IRF3 signaling (DiPerna, 2004), and encodes an anti-apoptotic bcl-2 (Aoyagi, 2007).
    • All of the characterized A52R family of genes inhibit NF-kB signaling (see Figure below). A52R affects p38 kinase activity, all the rest also inhibit IRF3 signaling and one (N1L) encodes a vbcl-2.
    • Despite this apparent redundancy, deletion of A52R, A46R, or N1L significantly attenuates infection. Our lab is attempting to understand the other mechanisms whereby members of this growing family of poxvirus genes function to modulate innate and adaptive immune responses.

    image of Poxvirus Inhibitin of Innate Immune Signaling

    In collaboration with the laboratories of other UMass faculty (Dr. Neal Silverman and Katherine Fitzgerald) we are attempting to define other mechanisms whereby N1L modulates innate immune responses. Dr. Fitzgerald’s laboratory is investigating the effects of RIG-I on viral replication. Two RNA-helicase and CARD-domain containing proteins, RIG-I and Mda5, are believed to recognize viral dsRNA in the cytoplasm. RIG-I and Mda5 are likely to play critical roles in the recognition of and response to many viral pathogens. RIG-I signals to MAVS/VISA/Cardif and then downstream to TBK-1.

    TLR3-mediated signal transduction relies entirely on the TIR-adaptor protein TRIF. Macrophages lacking the TRIF gene replicate vaccinia virus to 20-fold higher titers. This result highlights the importance of signaling downstream of TRIF for the protection against poxvirus infection. N1L inhibits TLR3-mediated signaling and N1L-mutant vaccinia virus has 104-fold decreased virulence in vivo, and 10-fold reduced replication both ex vivo and in a mouse model of vaccinia virus infection. The effect of N1L on poxvirus virulence in vivo may be even greater than the effect of losing TLR3 signaling on replication because N1L may inhibit both TLR3 and RIG-I mediated activation of NF-kB and IRF3.

    Collapse Bibliographic 
    Collapse 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.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Gammon DB, Duraffour S, Rozelle DK, Hehnly H, Sharma R, Sparks ME, West CC, Chen Y, Moresco JJ, Andrei G, Connor JH, Conte D, Gundersen-Rindal DE, Marshall WL, Yates JR, Silverman N, Mello CC. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection. Elife. 2014 Jun 25; 3. PMID: 24966209.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    2. Rus F, Morlock K, Silverman N, Pham N, Kotwal GJ, Marshall WL. Characterization of poxvirus-encoded proteins that regulate innate immune signaling pathways. Methods Mol Biol. 2012; 890:273-88. PMID: 22688773.
      Citations: 2     Fields:    Translation:HumansCells
    3. Mathew A, O'Bryan J, Marshall W, Kotwal GJ, Terajima M, Green S, Rothman AL, Ennis FA. Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus. PLoS One. 2008 Oct 02; 3(10):e3323. PMID: 18830408.
      Citations: 10     Fields:    Translation:AnimalsCells
    4. Chowdhry R, Marshall WL. Antifungal therapies in the intensive care unit. J Intensive Care Med. 2008 May-Jun; 23(3):151-8. PMID: 18474502.
      Citations: 1     Fields:    Translation:Humans
    5. Ilangovan R, Marshall WL, Hua Y, Zhou J. Inhibition of apoptosis by Z-VAD-fmk in SMN-depleted S2 cells. J Biol Chem. 2003 Aug 15; 278(33):30993-9. PMID: 12783893.
      Citations: 22     Fields:    Translation:AnimalsCells
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