Allergy and Immunology; Immunity; Inflammation; Macrophages; Gene Expression; Host-Pathogen Interactions; Adaptive Immunity
Molecular Virology: Virology laboratories
Skin Diseases Research Center, Yale
Research in this laboratory includes the following areas:
- Biology of Inflammation. Basic biology and inflammation and physiological functions of inflammatory response. Inflammation and metabolism.
- Infection biology. Host-microbe interactions. Modes of communication between micro-organisms and their hosts. Role of avoidance, resistance and tolerance in host defense from infection.
- Mechanisms of autoimmunity and allergy. Biology of allergens and allergic responses. Mechanisms of allergen sensing. Mechanisms of dysregulation of immune responses leading to autoimmune and allergic diseases.
- Principles of transcriptional response. Role of epigenetic regulation in developmental plasticity.
- Cellular heterogeneity. Cell fate decisions. Agent-based modeling.
Specialized Terms: Inflammation; Allergy; Immunology; Innate Immunity; Pathophysiology
Extensive Research Description
The disease state caused by microbial infection is a result of either microbial virulence or immunopathology (the host response to infection), or in some cases both. Thus immune sensing and responsiveness to infection are adjusted during evolution to achieve an optimal balance to maximize protection from infection, and to minimize the pathology caused by an overzealous immune response. This balance can presumably vary depending on infection. We are interested in studying the mechanisms (both hard-wired and adaptive) that allow for an optimal trade-off between these two conflicting goals. We are interested in understanding the role avoidance, resistance and tolerance as defense strategies.
Inflammation is a fundamental physiological process that underlies a multitude of normal and pathological conditions. We are studying both the basic biology of inflammation and the regulatory mechanisms that control initiation, quality and intensity of inflammatory responses. In particular, we are studying the links between inflammation and metabolism, inflammation and aging, and inflammation and cancer.
Control of adaptive immunity
Innate immune recognition plays a critical role in the control of adaptive immune responses. Multiple mechanisms underlie the connections between innate and adaptive immune systems, and most of them are poorly understood. We are studying basic mechanisms that couple innate immune recognition with activation and differentiation of adaptive immune responses. We are also studying the links between innate immune system and peripheral tolerance.
Control of gene expression
Stimulation of macrophages through TLRs leads to changes in the expression (induction and suppression) of hundreds of genes. These changes are effected through a diversity of mechanisms. Gene regulation occurs at multiple levels (activation of trasnscription factors, chromatin remodeling and histone modifications) and has both signal-specific and gene-specific components. Different subsets of TLR-inducible genes are subject to differential regulatory influences, which are dependent on the function of the products they encode. We are interested in the basic principles of inducible gene expression, which are currently poorly characterized.
We are studying the role of macrophages in maintenance of homeostasis and in physiological inflammation.
- Semaphorin 7A contributes to West Nile virus pathogenesis through TGF-β1/Smad6 signaling. Sultana H, Neelakanta G, Foellmer HG, Montgomery RR, Anderson JF, Koski RA, Medzhitov RM, Fikrig E. J Immunol. 2012 Sep 15;189(6):3150-8. doi: 10.4049/jimmunol.1201140. Epub 2012 Aug 15.
- Age-associated defect in human TLR-1/2 function. an Duin D, Mohanty S, Thomas V, Ginter S, Montgomery RR, Fikrig E, Allore HG, Medzhitov R, Shaw AC. J Immunol. 2007 Jan 15;178(2):970-5.