Scientific Program

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Dr. Steve Beverley (Washington University)

Many eukaryotic microbes possess RNA virus-like elements, the role and significance of which are usually unknown. We have studied the trypanosomatid protozoan parasite Leishmania in South America, which often bear the dsRNA virus LRV1, as a new paradigm of protozoal viral virulence. Like most Totiviruses, LRV1 is neither shed nor infectious, and thus may be viewed as a persistent endobiont. Perspectives on the importance of protozoal viruses changed upon discovery that L. guyanensis LRV1 is associated with hypervirulence and increased metastasis in animal models, the latter being a hallmark of the more severe forms of leishmaniasis (Ives et al. Science 2011). For Leishmania we developed RNA interference or antiviral tools for reproducibly generating isogenic lines lacking LRV1s (Brettmann et al PNAS 2016; Kuhlmann et al PNAS 2017). This has allowed extension of findings with L. guyanensis to L. braziliensis, the predominant agent of mucocutaneous leishmaniasis (MCL). In murine infections Leishmania bearing LRV1 display many alterations in host responses as shown by the work of Nicolas Fasel’s group, perhaps most significant being the induction of Type-I interferons (Rossi et al PNAS 2017). How these combine to promote LRV1-mediated hypervirulence is a key question.

One question is the contribution of LRV1 with Leishmania pathogenicity in human infections, where disease manifestations differ greatly from those seen in murine models, Many but not all studies have reported an association of LRV1 with more severe forms of leishmaniasis (Cantanhêde et al PLoS NTD 2015), and LRV1 was associated with increased relapse and/or treatment failures in human L. braziliensis-infected patients treated with pentavalent antimonials in Peru and Bolivia, as well as in L. guyanensis infections treated with pentamidine (Adauai et al & Bourreau et al. J. Inf. Dis 2016). The association of LRV1 with clinical drug treatment failure could serve to guide more effective treatments through the use of LRV1 inhibitors.

Currently we have embarked on a systematic survey of known and new viruses in Leishmania as well as their monoxenous insect trypanosomatid relatives and other parasites including the Apicomplexans Toxoplasma and Plasmodium, using a wide range of methods including next-gen RNA sequencing (Grybchuk et al PNAS 2018). This has greatly expanded our knowledge of the parasitic protozoal virome with the discovery of multiple new viruses, several of which may play similar roles impacting virulence through different mechanisms. The properties, evolution and potential contributions of these to virulence and biology will be discussed.

Dr. Marion Pepper (University of Washington)

Dr. Marion Pepper earned her Ph.D. in Immunology in 2006 from the University of Pennsylvania School of Medicine. Her work there focused on the development of the CD4+ T cell response to the eukaryotic parasite, Toxoplasma gondii in the laboratory of Dr. Christopher A. Hunter. She continued to study the adaptive immune response, specifically focusing on memory lymphocyte differentiation and function in Dr. Marc K. Jenkins’ lab at the University of Minnesota. In 2011, she joined the faculty of the Department of Immunology at the University of Washington in Seattle as an Assistant Professor. The overarching goals of her laboratory are to understand how to regulate immune cell differentiation such that memory responses against infections can be optimized, while those against allergy can be suppressed. Her studies have revealed key differentiation programs and functions of both memory CD4+ T cells and B cells in response to pathogens and allergens. In 2017, she was awarded the Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases award and was promoted to Associate Professor. She enjoys living in Seattle with her husband, two daughters, one very large dog and a recently acquired puppy.

Dr. Donna Farber (Columbia University)

Donna L. Farber, Ph.D. is the George H Humphreys, II Professor of Surgical Sciences (in Surgery) and Professor of Microbiology and Immunology at Columbia University. The focus of Dr. Farber’s research is on adaptive immunity, particularly to virus infections and how T cell differentiate and generate long-term immunological memory in diverse tissues sites. Dr. Farber’s laboratory identified subsets of tissue-resident memory T cells in the lung that mediate protective immunity to respiratory virus infection and has led an initiative in translational immunology to dissect human immune responses in tissues throughout the body, in multiple mucosal and lymphoid tissues from individual organ donors of all ages. She has also made important contributions to understanding how T cells seed tissues and mediate responses to viruses during different life stages including infancy. Dr. Farber leads NIH/NIAID-funded Program grants on human immunity, anti-viral responses and is part of the Human Immunology Project Consortium (HIPC), as well as the NIH/NHLBI consortium on human lung aging. In addition to the NIH, her research is supported by the Helmsley Charitable trust and the Chan-Zuckerberg seed network for the Human Cell Atlas. She has over 140 publications and has served on numerous advisory committees for the NIH, American Association of Immunologists, Federation of Clinical Immunology Societies and others.