Mechanisms of immune regulation in the skin

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DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an academic career in the field of cutaneous immunology. The candidate graduated from the Medical Scientist Training Program (MSTP) at the Medical College of Wisconsin. His graduate work focused on basic mechanisms of immune tolerance, and upon completion of his doctoral work, the candidate combined his 3rd and 4th years of medical school with a post-doctoral research project on immune regulation in the skin. He recently graduated from a dermatology residency at UCSF where he trained in the Molecular Medicine Physician-Scientist Training Pathway. During his residency, and over the past year as a UCSF junior faculty member, the candidate established a novel mouse model to study T cell-mediated immune responses in the skin. Through the proposed training program, the candidate will expand upon his scientific skills and become and independent investigator studying the basic immunology of the skin. He will accomplish this through coursework, participation in seminars and conferences, national presentations, and engagement in a mentored research project. Dr. Abul Abbas will mentor the candidate's scientific development. Dr. Abbas is Professor and Chairman of the Department of Pathology at UCSF and a world-renowned leader in the field of immune tolerance. His record of mentoring postdoctoral fellows and graduate students is outstanding. To enhance the candidate's training, an advisory committee of highly-regarded senior scientists will provide scientific and career advice. The advisory committee will consist of an immunologist (Dr. Mark Anderson, MD, PhD., Assistant Professor,of Medicine and Endocrinology at UCSF) a cutaneous biologist (Dr. Thea Mauro MD, Professor of Dermatology, UCSF), and a cutaneous geneticist (Dr. Pui-Yan Kwok MD, PhD., Professor of Dermatology, UCSF). Research will focus on uncovering basic mechanisms of immune regulation in the skin. Currently, little is known about how immune responses are controlled in peripheral tissues. Using a novel mouse model of CD4+ T cell-mediated inflammation, the research project will dissect the mechanisms responsible for attenuating these reactions in the skin. The work will focus on regulatory T cells and the PD-1/PD-L1 pathway. In addition, differential gene expression analysis will be utilized to uncover novel mechanisms of both T cell- mediated and keratinocyte-mediated immune regulation. The project will translate results obtained in mice to humans with inflammatory skin disease. The aggregate data will provide a major advancement in our understanding of how T cell-mediated immune responses are regulated in the skin, and have the potential to establish a foundation for novel therapeutic approaches for inflammatory skin disease. The proposed training program draws on the combined resources of the Abbas Laboratory, the UCSF Immunology Program, and the UCSF Department of Dermatology. This will provide an ideal setting for the candidate's transition to an independent investigator. PUBLIC HEALTH RELEVANCE: Chronic inflammatory skin diseases such as psoriasis and the eczematous dermatoses are associated with a significant amount of morbidity and markedly reduced health-related quality of life. The psychological and economic burden of these diseases on patients is profound. The research outlined in this proposal aims to enhance our understanding of these diseases and provide a foundation for novel therapeutic strategies.