Genetic Analysis of the TNF Pathway in Psoriasis

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in the field of psoriasis genetics. The candidate completed his medical studies at Harvard, performed a year of clinical research training at the NIH, and recently graduated from a dermatology residency at UCSF. Over the past year, as a UCSF junior faculty member, the candidate has contributed to the discovery of several psoriasis genes through his establishment of a large psoriasis patient database. Through the proposed training program, the candidate will expand upon his scientific skills to become an independent investigator in human genetics. He will accomplish this through coursework, participation in seminars and conferences, national presentations, and engagement in a mentored research project. Dr. Pui-Yan Kwok will mentor the candidate's scientific development. Dr. Kwok is a recognized leader in the field of genetics and genomics. Dr. Kwok serves as the Henry Bachrach Distinguished Professor at UCSF and is a founding member of the International HapMap Consortium. His record of mentoring postdoctoral fellows and graduate students is superb. 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 two geneticists (Anne Bowcock, PhD., Joint Director for Human Genetics at Washington University, and Lindsey Criswell, MD, MPH, Professor of Medicine and Rheumatology at UCSF) and an immunologist (Averil Ma, MD, Professor of Medicine and Gastroenterology at UCSF). Of note, Dr. Criswell and Dr. Ma's own research interests are integrally tied to the candidate's proposed research plan; thus, the candidate will receive closer-than-usual feedback through a unique "team science" approach. Research will focus on the role of TNF pathway gene variants in psoriasis. Recent results from a large genome wide association study in psoriasis demonstrate that two genes in the TNF pathway, TNFAIP3 and TNIP1, are major risk factors for the development of psoriasis. The research project will perform fine mapping of these two genes to identify causal variants, and additionally examine other genes in this pathway for genetic association. High throughput genotyping, DNA sequencing, and copy number assays will be employed. The aggregate data will provide the first detailed picture of TNF pathway genes in psoriasis. The proposed training program draws on the combined resources of the UCSF Institute for Human Genetics, UCSF Department of Dermatology, and UCSF Psoriasis Center. This will provide an ideal setting for the candidate's maturation into an independent investigator.