Joshua W. Knowles, MD, PhD, Assistant Professor, Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine
Research Description: Dr. Knowles' research has been centered on understanding the genetic basis for insulin resistance (IR). He has helped to lead a large international consortium (GENESIS) that has identified novel insulin sensitivity genes and is focused on understanding the causal mechanisms for these genes. He has also pioneered in the creation of induced pluripotent cell models of IR to serve as a resource for the greater scientific community. Knowles is also a clinician with a strong interest in understanding the cardiovascular implications of insulin resistance specifically statin-associated type 2 diabetes. He has had long-term and productive collaborations with other members of the SDRC, detailed below and in his biosketch. Dr. Knowles is co-leader of the Metabolism and Signaling in Diabetes Research Affinity Group of the SDRC.
Selected relevant publications (Stanford DRC members in BOLD):
1. Knowles JW, Xie W, Zhang Z, Chennemsetty I, Assimes TL, Paananen J, Hansson O, Pankow J, Goodarzi MO, Carcamo-Orive I, Morris A, Chen Y-DI, Mäkinen V-P, Ganna A, Guo X, Abbasi F...(> 5 authors)...Schadt EE, Rotter JI, Sinaiko A, Reaven G, Yang X, Hsiung CA, Groop L, Cordell HJ, Laakso M, 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(4):1739-51, 2015.
2. Dimas AS*, Lagou V*, Barker A*, Knowles JW*, Magi R…(>15 authors)... Ingelsson E, McCarthy MI, Prokopenko I. Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes 63: 2158-2171, 2013 * co-first author
3. Xie W, Wood AR, Lyssenko V, Weedon MN, Knowles JW, Alkayyali S, Assimes TL, Quertermous T, Abbasi F,..(12 authors).. Frayling TM, Walker M. Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes. Diabetes 62:2141-2150, 2013.
4. Kohli P, Knowles JW*, Sarraju A, Waters DD, Reaven G. Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated Patients (From the Treating to New Targets (TNT) and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trials). Am J Cardiol 11:1275-1281, 2016.
5. Knowles JW, Assimes TL, Tsao PS, Natali A, Mari A, Quertermous T, Reaven GM, Abbasi F. Measurement of insulin-mediated glucose uptake: Direct comparison of the modified insulin suppression test and the euglycemic, hyperinsulinemic clamp. Metabolism 62:548-553, 2013.
6. Fall T, Xie W, Poon W, Yaghootkar H, Mägi R; GENESIS consortium, Knowles JW, Lyssenko V, Weedon M, Frayling TM, Ingelsson E. Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes. Diabetes 64: 2676-2684, 2015.