Thomas Quertermous MD, Professor, Department of Medicine; William G. Irwin Professor in Cardiovascular Medicine, Stanford Unviersity School of Medicine
Research Description: Dr. Quertermous has had a longstanding interest in insulin resistance and adult onset diabetes (T2D), focusing primarily on the identification of genes that mediate the variance in insulin sensitivity, and thus are likely contributors to insulin resistance. He created the Genetics of Insulin Sensitivity (GENESIS) consortium when it first became apparent that genome-wide association (GWA) studies of T2D would not fully address the genetic basis of insulin resistance. The goal of this study has been to use insulin clamp measures as the physiological variable of insulin sensitivity for application of GWA methodology, and he has enlisted collaborating investigators worldwide with significant numbers of subjects evaluated by insulin clamp for which DNA is also available. Dr. Quertermous has conducted a GWA study in over 2000 subjects, and is currently working to replicate the top findings in additional subjects with insulin clamp measures of insulin sensitivity. One near genome-wide associated variant and related gene identified through these studies is currently being investigated with follow-up in vitro and animal model studies. As PI of the Genetics of Insulin Sensitivity iPSC (GENESiPS) study, Dr. Quertermous leads a collaborative effort to develop 200 iPSC lines from subjects of the GENESIS consortium, and this group is differentiating these cells into metabolic and vascular cell types in an effort to map insulin sensitivity genes. These studies have already shown that variance in the insulin mediated glucose uptake is a cell autonomous phenotype highly correlated to measures of insulin sensitivity in vivo.
Selected relevant publications (Stanford DRC Members in BOLD):
1. Suhre K,…Quertermous T,… Gieger C. Human metabolic individuality in biomedical and pharmaceutical research. Nature 477:54-60, 2011.
2. Dastani Z,...Quertermous T, ...Kathiresan S. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLOS Genet 8:1002607, 2012.
3. Knowles JW, Xie W, Zhang Z, Chennemsetty I, Assimes TL, Paananen J, Hansson O, Pankow J, Goodarzi MO, Carcamo-Orive I, Morris A, Yii-Der I. Chen Y-DI, Mäkinen V-P, Ganna A, Guo X, Abbasi F, Greenawalt DM, Lum P, Molony C, Lind L, Lindgren C, Raffel LJ, Tsao PS, The RISC Consortium, The ULSAM Study, The EUGENE2 Study, The GUARDIAN Consortium, The SAPPHIRe Study, Schadt EE, Rotter JI, Sinaiko A, Reaven G, Yang X, Hsiung CA, Groop L, Cordell HJ, Laakso M, Ke Hao K, Ingelsson E, Frayling TM, Weedon MN, Walker M, Quertermous T. Identification and validation of NAT2 as an insulin sensitivity gene. J Clin Invest 125:1739-51, 2015.
4. Chennamsetty I, Michael Coronado M, Contrepois K, Keller MP, Carcamo-Orive I, Sandin J, Fajardo G, Whittle AJ, Fathzadeh M, Snyder M, Reaven G, Attie AD, Bernstein D, Quertermous T, Knowles JW. Nat1 deficiency is associated with mitochondrial dysfunction and excerise intolerance in mice. Cell Reports, 17:527-540, 2016.