Robert Mcgehee Jr Institution Verified

OverviewAI-generated summary

Robert Mcgehee Jr. leads a research program focused on diabetes and obesity, with a translational and basic science approach. He holds a position as Distinguished Professor in the Department of Pediatrics at the University of Arkansas for Medical Sciences (UAMS) College of Medicine and Arkansas Children’s Hospital, and also serves as the Dean of the UAMS Graduate School. His work has been supported by the National Institutes of Health (NIH).

Mcgehee is a Co-Principal Investigator on two federal grants. One is the "The University of Arkansas for Medical Sciences Initiative for Maximizing Student Development Program," funded by the NIH/National Institute of General Medical Sciences for $445,062. The second is the "UAMS Summer Undergraduate Research Program to Increase Diversity in Research," funded by the NIH/National Heart Lung and Blood Institute for $105,521. He also leads a research group.

In addition to his research, Mcgehee has extensive experience in infrastructure development, mentoring, career development, and grant writing. He is the associate fellowship director for the neonatal/perinatal subspecialty training program in the Department of Pediatrics and mentors research projects for pediatric fellows. He was also instrumental in establishing the UAMS Clinical and Translational Science Award (CTSA) formal training programs, including graduate certificate, MS, and PhD programs, serving as the original Director of the Education, Training, and Career Development Core and Director of its KL2 Training Program for the first six years of the TRI.

Research Overview

A. Personal Statement I am currently a Professor of Pediatrics/Neonatology in the UAMS College of Medicine and Arkansas Children’s Hospital, and Dean of the UAMS Graduate School. I have had a longstanding NIH-funded translational/basic science research program in diabetes and obesity and in addition to the current IMSD non-competing renewal, I serve as a Co-PI on an NHLBI SURP award to promote diversity among undergraduate students with interests in health care. I am the associate fellowship director for the neonatal/perinatal subspecialty training program in the Department of Pediatrics and help mentor research projects for pediatric fellows. I am also very engaged with our CTSA award that established the UAMS TRI, and for the first six years of the TRI was the original Director of the Education, Training, and Career Development Core, as well as Director of its KL2 Training Program. In this role, I helped establish the formal CTS training program that includes the Graduate Certificate, MS, and PhD graduate programs. Combined throughout my career, I have had a broad range of successful experience with infrastructure development, mentoring, career development, grant writing, and translational research C. Contributions to Science 1. My lab has always focused in some degree the cellular differentiation of adipocytes. Initially, this was through the use of in vitro murine cell lines such as 3T3-L1’s. We worked on identifying molecular mechanisms that promoted the adipocyte lineage and identified unique molecules that were required for differentiation. These studies were the first to demonstrate a role for two members of the Retinoblastoma tumor suppressor gene family, p107 and p130, in regulating adipogenesis. a. McGehee Jr. RE and Habener JF. Nuclear protein DSEB binds to a differentiation-specific element in the promoter of the angiotensinogen gene required for the irreversible induction of gene expression during differentiation of 3T3-L1 adipoblasts to adipocytes. Molec Endocrinology 1995; 9:487-501. b. Richon VM, Lyle RE and McGehee Jr. RE. Regulation and expression of retinoblastoma proteins p107 and p130 during 3T3-L1 adipocyte differentiation. J Biol Chem 1997; 272:10117-10124. c. Liu K, Guan Y, MacNicol M, MacNicol A and McGehee Jr. RE. Early expression of p107 is associated with 3T3-L1 adipocyte differentiation. Mol Cell Endocrinol 2002; 194:51-61. d. Prince AM, May JM, Burton G, Lyle RE and McGehee Jr. RE. Specific degradation of the p130 Tumor suppressor gene by the 26S proteasome during 3T3-L1 adipocyte differentiation. Biophys Res Comm 2002; 290:1066-71. 2. We went on to show that these proteins were differentially regulated in murine myoblast differentiation and that in aging myoblasts, the pattern of expression was similar to adipocytes; and that these proteins had similar roles in the differentiation of adult derived human adipose stem cells (ADHAS) isolated from lipoaspirates collected following elective liposuction surgery. a. Guan Y, Taylor-Jones JM, Peterson CA and McGehee, Jr., RE. p130/p107 expression distinguishes adipogenic potential in primary myoblasts based on age. Biochem Biophys Res Comm 2002; 296:1340-1345. b. Taylor-Jones JM, McGehee Jr. RE, Rando TA, Lecka-Cernik B, Lipschitz DA, Peterson CA. Activation of an adipogenic program in adult skeletal myoblasts with age. Mechanisms of Ageing and Development 2002; 123:649-661. c. Vertino AM, Taylor-Jones JM, Longo KA, Bearden ED, Lane TF, McGehee RE Jr, Macdougald OA, and Peterson CA. Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts. Mol Biol Cell 2005; 16:2039-48. PMCID: PMC1073681 d. Ross AS, Tsang R, Shewmake K, McGehee RE Jr, Expression of p107 and p130 during human adipose-derived stem cell adipogenesis. Biochem Biophys Res Comm 2008; 366:927-931. PMCID: PMC2877912 3. In collaboration with Drs. Philip Kern and Charlotte Peterson, we began investigating mechanisms of how adipose and adipocytes contribute to insulin resistance. a. Yao-Borengasser A, Rasouli N, Varma V, Miles LM, Phanavanh B, Starks, TN, Phan J, Spencer, HJ III, McGehee RE Jr, Reue K, Kern PA. Lipin expression is attenuated in adipose tissue of insulin-resistant human subjects and increases with peroxisome proliferator-activated receptor gamma activation. Diabetes 2006; 55:2811-2818. b. Spencer M, Unal R, Zhu B, Rasouli N, McGehee RE Jr, Peterson CA, Kern PA. Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance. J Clin Endocrinol Metab 2011 96:E1990-8. c. Kern PA, Spencer M, Finlin B, Unal R, Zhu B, Morris A, Shipp L, Adu A, Erfani R, Campbell M, McGehee RE Jr, Peterson CA. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes 2013 62:1709-1717. d. Kern PA, Finlin BS, Zhu B, Rasouli N, McGehee RE Jr, Westgate PM, Dupont-Versteegden EE. The effects of temperature and seasons on subcutaneous white adipose tissue in humans: evidence for thermogenic gene induction. J Clin Endocrinol Metab. 2014 99:E2772-9. 4. To extend our investigations into muscle-adipose interactions, we more recently developed a Transwell membrane co-culture model plating ADHAS derived adipocytes and myoblast differentiated from muscle biopsies on the two surfaces. By seeding human macropahges on top of the adipocytes, we have been able to study the mechanisms by which these cells interact with each other in the presence or absence of inflammation in contributing to insulin resistance, metabolic syndrome and diabetes. a. Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, NolenGT, Nagarajan R, Spencer III HJ, Lee MJ, Fried SK, McGehee RE Jr*, Peterson CA* and Kern PA* (*co senior authors). Thrombospondin-1 (TSP1) is an adipokine associated with obesity, adipose inflammation and insulin resistance. Diabetes 2008; 57:432-439. PMCID: PMC2877915 b. Varma V, Yao-Borengasser A, Rasouli N, Nolen GT, Phanavanh B, Starks T, Gurley C, Simpson P, McGehee RE Jr, Kern PA, Peterson PA. Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am J Physiol Endocrinol Metab 2009; 296:E1300-10. PMCID: PMC2692398 c. DiGregorio GB, Yao-Borengasser, Rasouli N, Varma V, Lu T, Miles LM, Ranganathan G, Peterson CA, McGehee RE Jr, and Kern PA. The expression of CD 68 and macrophage chemoattactant protein-1 genes in human adipose and muscle tissue: association with cytokine expression, insulin resistance and reduction by piaglitazone. Diabetes 2005; 54:2305-2313. d. Finlin BS, Zhu B, Starnes CP, McGehee RE Jr, Peterson CA, Kern PA. Regulation of Thrombospondin-1 expression in alternatively activated macrophages and adipocytes: role of cellular crosstalk and omega-3 fatty acids. J Nutr Biochem 2013 24:1571-1579.