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Clinical Systems Biology Research

Current Research

  • Women vs. Men with GWI: Differences in Computational Models and Therapeutic Target
    VA MERIT

    We hypothesize that GWI affects regulatory function differently in women than in men, with implications on therapeutic management. The objective of this study is to improve our understanding of GWI pathogenesis in women by: (i) integrating data across several of the body’s regulatory systems, and (ii) mapping of dysfunctional signaling networks in GWI in each sex.
  • Microbial Translocation in Chronic Fatigue Syndrome
    NIH R21

    To investigate the involvement of microbial translocation (MT) from the gut as a potential mechanism of disease progression and persistence in chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME). Specifically, survey microbial translocation into peripheral blood of the biomarkers, lipopolysaccharide (LPS) and soluble CD14 (sCD14): at baseline, at 18 months as well as at two intervening time points corresponding to an episode of severe symptom onset. Then describe biomarker involvement in disease circuitry of immune, autonomic, neuroendocrine markers and clinical biomarkers using a systems biology framework.
  • Understanding Gulf War Illness: An Integrative Modeling Approach
    DoD CDMRP/ GWIRC

    Integrate two animal models of GWI with human clinical data to pinpoint the underlying mechanisms of disease and target treatment more effectively to re-establish normal well-coordinated signaling interactions. Specifically, our more detailed understanding of the dysfunction associated with key metabolic pathways involved in GWI would greatly expedite the identification of promising biomarkers for improved diagnosis over the short-term as well as selection and testing of more targeted therapeutic interventions over the longer term that will address the underlying mechanisms of disease.
  • Gender Differences in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
    NIH RO1
    We aim to understand the mediators of persistence and relapse in men with ME/CFS, as we have in women. We will approach this by: (i) integration across several of the body’s regulatory systems of data and knowledge collected from disparate sources, and (ii) mapping of the coordinated interactions between these physiologic systems and the potential for dysfunctional signaling networks. This project will extend this modeling of immune regulatory pathways and pathways that regulate latent viral expression in a way that will enable us to compare gender differences in illness mechanisms and explore gender-specific therapeutic targets.
  • Epigenetic Mediation of Endocrine and Immune Responses in an Animal Model of Gulf War Illness
    DoD CDMRP/GWIRP
    The overall objective is to identify epigenetic mechanisms of altered Hypothalamic-Pituitary-Adrenal (HPA) axis and immune signaling in a mouse model of environmental exposures linked to GWI. DNA methylation and histone modifications will be examined in peripheral blood and the brain using a high-throughput genome-wide approach. This proposal builds on a funded GWIRP Consortium project examining gene regulatory dynamics in a mouse model of exposure to a sarin surrogate under stress/immune challenge.

Past Research

  • Molecular Patterns of Persistent Immune Activation in a Post-infectious Adolescent Cohort
    CFIDS ASSOCIATION OF AMERICA

    To describe deviations in endocrine-immune status and signaling that occur with onset and progression of post-infectious chronic fatigue syndrome (PI-CFS) for early detection and objective diagnosis.
  • Post-exertion malaise in CFS: A systems biology approach to understanding brain, inflammation and behavior interactions (Collaboration Univ. of Wisconsin)
    CFIDS ASSOCIATION OF AMERICA
    The main goal is to determine the dynamic relationships between brain structure and function, gene expression for sensory, adrenergic, and immune function and self-reported symptoms in chronic fatigue syndrome (CFS/ME) using an exercise model in a systems biology framework.
  • Study of Chronic Fatigue Syndrome using comprehensive molecular profiling with network and control theory 
    NIH R01 

    To improve our understanding of CFS pathogenesis by: (i) integrating data and knowledge collected from disparate sources across several of the body’s regulatory systems,  (ii) mapping the interactions that emerge at multiple scales of biology and identifying potentially altered “wiring” in these signaling networks specific rapid response to exercise in CFS.
  • Theory-driven Models for Correcting “Fight or Flight” Imbalance in Gulf War Illness 
    DoD CDMRP/ GWIRP
    The goal of this project is to create a comprehensive engineering model of endocrine-immune interaction dynamics in order to identify (i) theoretical failure modes of the HPA-immune axis that align with GWI, and (ii) promising treatment strategies that exploit the regulatory dynamics of these systems to reset control of the HPA-immune axis to normal.
  • The Use of Comprehensive Molecular Profiling with Network and Control Theory to Better Understand Gulf War Illness and Model Therapeutic Strategies 
    DoD CDMRP/ GWIRP
    We propose that GWI and CFS result not only from failure of individual neuroendocrine and immune components but perhaps more importantly from a significant deterioration of their regulatory interaction as a result of infectious, environmental or psychological insult. This study aims to verify this hypothesis by monitoring levels of immune and neuroendocrine markers in blood prior, during and after an exercise challenge.
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