Research Interests

There are several areas of research interests pursued in this laboratory, including:

1. Innate immune recognition
2. Host-pathogen interactions
3. Biology of inflammation
4. Control of adaptive immunity
5. Cell biology of signal transduction
6. Control of gene expression
7. Cancer biology

Innate immune recognition

The innate immune system relies on several distinct strategies of recognition, including pattern recognition and missing self recognition. We are interested in defining cellular and molecular mechanisms of innate immune sensing and signaling. There are several different classes of receptors involved in innate immune recognition. We are interested in the general design of the recognition and signaling modules of the innate immune system, their functional relationships, their roles in host defense and in control of adaptive immunity, and their contributions to immunopathology.

Host-Pathogen interactions

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 of virulence in host-pathogen interactions and the effect of microbial virulence on innate and adaptive immunity. We are also studying the affect of infection on the immune system and how the immune system handles co-infections.

Inflammation

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.

Cell biology of signal transduction

Most of what we know about cell signaling is based on biochemical and genetic studies. While these approaches provide essential information about the composition of signaling pathways, much less progress has been made in understanding the functional organization of signaling pathways, especially in the context of basic cell biological processes, such as protein sorting and vesicular trafficking. We are interested in basic principles that govern the cell biology of signaling transduction pathways.

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.

Cancer biology

We are studying the mechanisms whereby cancer cells can sense their 'oncogenic state' and communicate it to other cells of the host. We are also studying the role of inflammation and tissue repair in tumor progression.