报告题目：From GWAS to Functional SNPs and to Mechanisms

报告人：Dr. Gang Li, Assistant professor in the Aging Institute at University of Pittsburgh.

主持人：钱旻 教授

报告时间：12月18日 下午13:30

报告地点： 生命科学学院534小会议室

主办单位：生命科学学院

 

报告人简介：Dr. Gang Li is an assistant professor in the Aging Institute at University of Pittsburgh. He received both his B.S. degree in Biology and his M.A degree in developmental biology at East China Normal University and acquired his Ph.D. degree in molecule biology at Brown University. Dr. Li had his first postdoctoral training in Dr. Frederick Alt’s lab at HHMI/Harvard Medical School where he studied DNA double-strand break repair in terms of V(D)J recombination and class switch recombination during immunoglobulin production. Later, Dr. Li joined Dr. Robert Plenge’s lab in Brigham and Women’s Hospital/Harvard Medical School to help identify new drug targets in rheumatoid arthritis based on GWAS analysis. During this period, Dr. Li became interested in functional studies in the post GWAS era and developed a set of novel high throughput screening techniques to study the mechanisms underlying the contribution of disease-associated non-coding SNPs revealed by GWAS. The diseases that are currently studied in Dr. Li’s lab are aging-related diseases such as Alzheimer's disease, cardiovascular disease and cancers. The goal of Dr. Li’s study is to use human genetics (GWAS) as a guide to identify new drug targets and ultimately apply these new findings to develop precision drugs for aging-related human diseases. Currently, Dr. Li’s studies are supported by three NIH grants and grants from Arthritis National Research Foundation and National Multiple Sclerosis Society.

 

报告内容简介：Genome wide associat ion studies (GWAS) identify numerous disease-associated, non-coding single nucleotide polymorphisms (SNPs), however, GWAS cannot distinguish the functional SNPs (fSN P) from the many non-randomly associated SNPs that are in linkage disequilibrium. To meet this challenge, we developed SNP-sequencing (SNP-seq) to experimentally identify fSNPs in a high throughput (HTP) way . Moreover, we also developed Flanking Restriction Enhanced DNA pulldown-mass spectrometry (FREP-MS) to identify regulatory proteins that specifically bind to fSNPs with great efficiency. We demonstrated the feasib ility of these techniques in an experimenta l trial on a CD40 locus that is associated with multiple autoimmune diseases such as rheumatoid arthritics (RA) and multiple sclerosis (MS). We identified three fSNPs together with four regulatory proteins that regulate CD40 expression via the fSNPs . We also performed a HTP screen by identifying 148 potential fSNPs out of 608 juvenile idiopathic arthritis (JIA)-associated SNPs. We proved multiple fSNPs together with the regulatory proteins on the STAT4, TyK2 and SH2B3 loc i that are also associated with other autoimmune diseases such as RA and type I diabetes (T1D). In summary, we developed a potentially transformative approach to study autoimmune diseases in the post GWAS era, which will accelerate our understanding of the mechanisms underlying the contribution of disease-associated non-coding fSNPs.