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Directory >> Joshua T. Schiffer, MD, MSc

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Joshua T. Schiffer, MD, MSc

  • Assistant Professor, Division of Allergy and Infectious Diseases, Department of Medicine
  • University of Washington
  • Assistant Member, Vaccine and Infectious Diseases Division and Clinical Research Division
  • Fred Hutchinson Cancer Research Center

The aim of my research program is to gain a better understanding of the quantitative features of human pathogens and immune responses. In close collaboration with colleagues at the Fred Hutchinson Cancer Research Center and the University of Washington, I design mathematical models that capture growth and decay kinetics of infectious organisms. My models attempt to replicate detailed empirical datasets, and in turn, are used to inform subsequent human studies and laboratory experiments. At its core, my group's research tries to identify conditions that predict either containment or expansion of human pathogens.

A major focus in my group is the evaluation of interactions between herpes simplex virus-2 (HSV-2) and host immune response in the human genital tissues. HSV-2 is a globally important infection that is the leading cause of genital ulcers, and is also a critical risk factor for HIV acquisition and transmission. In addition, HSV can cause severe disease in persons with immunosuppression due to HIV, organ transplantation, stem cell transplantation, or other immuncompromised conditions. I design detailed clinical studies to capture the dynamic features of the frequent, heterogeneous shedding episodes that are a key feature of chronic HSV-2 infection in humans, and to characterize the dynamics of the HSV-specific lymphocyte response to viral replication in the genital tract. I synthesize this virologic and immunologic data into mathematical models of pathogenesis, which I continually update as our group accrues new data and new ideas. While our models and empirical data suggest extraordinarily rapid expansion of HSV-2 across the genital tract, each shedding episode is ultimately contained and significant immune pressure is evident within hours of shedding episode initiation. We continue to explore the spatial immune mechanisms that lead to this balance between virus and host.

My group is involved in a number of other projects, all of which involved the synthesis of novel clinical and laboratory datasets with mathematical models. These projects include: pharmacokinetic and pharmacodynamic evaluation of antiviral therapies; curative approaches for chronic viral infections such as hepatitis B, HSV and HIV; role of tissue resident T-cells in containing infection; transmission dynamics of viruses in newborns; and dynamics of bacterial species that compromise the human micro biome. Please visit my lab site for more details.


Selected Publications


Schiffer JT, Abu-Raddad L, Mark KE, et al. Frequent release of low amounts of herpes simplex virus from neurons: results of a mathematical model. Sci Transl Med. 2009;1(7): 7ra16.
PubMed Abstract


Schiffer JT, Abu-Raddad L, Mark KE, Zhu J, Selke, S, Koelle, DM, Wald A and Corey L. Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes. Proc Natl Acad Sci. 2010; 107(44): 18973-8. PMID: 20956313, PMCID: PMC2973882.
• PubMed Abstract


Schiffer JT, Swan D, Al Sallaq R, et al. Rapid localized spread and immunologic containment define Herpes simplex virus-2 reactivation in the human genital tract. Elife. 2013; 2: e00288.
PubMed Abstract


Schiffer JT, Swan D, Stone D, Jerome K. Predictors of hepatitis B cure using gene therapy to deliver DNA cleavage enzymes: a mathematical modeling approach. PLoS Comput Biol. 2013 Jul;9(7):e1003131. PMID: 23861664, PMCID: PMC3701691.
• PubMed Abstract


Schiffer JT, Swan D, Corey L, Wald A. Rapid viral expansion and short drug half-life explain the incomplete effectiveness of current Herpes Simplex Virus-2 directed antiviral agents. Antimicrob Agents Chemother. 2013 Dec;57(12):5820-9. PMID: 24018260, PMCID: PMC3837890.

Matrajt L, Younan P, Kiem HP, Schiffer JT,. The majority of CD4+ T-cell depletion during acute SHIV89.6P infection occurs in uninfected cells. JVI (in press) PMID: 24390339. PMCID: PMC Journal - In Process.
• PubMed Abstract

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