Scientist Profile

I joined Genentech as a scientist in 2001, after studying signal transduction and transcriptional networks in T helper cell differentiation. Genentech provides a very special environment that facilitates the integration of basic scientific research with therapeutic innovation. Scientists from different disciplines are encouraged to join forces to pursue fundamental molecular mechanisms underlying various diseases with unmet medical needs.

My Focus

My lab is interested in understanding the crosstalk between immune system and various tissue cell types, especially epithelial cells, during autoimmune and infectious diseases.

One of the questions we have asked is how the immune infiltration, particular with T cells, in epidermis and dermis during the pathogenesis of psoriasis resulting in epidermal keratinocytes hyperplasia and abnormal differentiation.

We have identified Th17 cells as one of the major T helper subsets migrating into psoriatic skin. Th17 cells produce IL-22 that is a major leukocyte cytokine targeting tissue epithelial cells. IL-22 induces many pathogenic features, observed in psoriatic skin, from epidermal keratinocytes. Thus, IL-22 is one of the important mediators from immune system to epithelial cells during the pathogenesis of psoriasis.

Recently, we have been focused on the role of Th17 cells in regulation of mucosal immunity. We are interested in the relationships among luminal flora, intestinal epithelial cells, and leukocytes during diseases such as IBD. We try to understand the mechanisms on how different microbes can trigger distinct downstream immune responses, for example the induction of IL-17 and IL-22 from innate lymphocytes and T cells during Citrobactor rodentium infection. In addition, we found that cytokines targeting intestinal epithelial cells not only regulate innate host defense mechanisms, but also contribute to the formation of tissue embedded lymph follicles, such as isolated lymph follicles (ILF) and colonic patches.

My lab is also interested in the regulation and function of various T helper subsets in autoimmune diseases. We identified that IL-22 is an effector cytokine produced by Th17 cells and the regulation of IL-22 is different from the regulation of IL-17 during the development of Th17 cells. Both IL-23 and IL-6 are able to induce IL-22 production in vitro. IL-23 is also required for IL-22 production from many disease models in vivo. Interestingly while TGF-b is required for IL-17 production from T cells, it actually inhibits the production of IL-22 from Th17 cells. We are currently in the process of dissecting the molecular mechanism of the differential regulation of these cytokines in T cells.

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Publications & Recognition

• Regulation and Functions of IL-10 Family Cytokines in Inflammation and Diseases
• Annu Rev Immunol, 2011
• Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG
• View Abstract on PubMed

• Even neurons are excited by Th17 cells
• Immunity, 2010. 33(3):298-300
• Egen JG, Ouyang W
• View Abstract on PubMed

• Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages
• Proc Natl Acad Sci., 2010, 107(19):8712-7
• Wong K, Valdez PA, Tan C, Yeh S, Hongo JA, Ouyang W
• View Abstract on PubMed

 

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