Andrew Stewart, MD
- Director, Diabetes, Obesity and Metabolism Institute
Irene and Dr. Arthur M. Fishberg Professor of Medicine (Endocrinology, Diabetes and Bone Disease)
Research Topics:Autoimmunity, Cell Biology, Cell Cycle, Cell Division, Cellular Differentiation, DNA Replication, Diabetes, Gene Discovery, Gene Expressions, Gene Therapy, Genomics, Growth Factors and Receptors, Hormones, Immunosuppression, Insulin, Knockout Mice, Obesity, Oncogenes, Phosphorylation, Protein Kinases, Proteomics, Receptors, Transgenic Mice, Transplantation, Tumor Suppressor Genes
Dr. Andrew Stewart’s research focuses on understanding and developing novel means for inducing the replication and regeneration of insulin-producing pancreatic beta cells. As Chief of the Division of Endocrinology and Metabolism at the University of Pittsburgh School of Medicine, Dr. Stewart and his research team were the first to demonstrate that adult human beta cells could be induced to replicate at substantial rates. Three long-time colleagues from that group are joining him: Donald K. Scott, PhD; Adolfo García-Ocaña, PhD; and Rupangi Chhaya Vasavada, PhD, as Professors in the Division of Endocrinology, Diabetes and Bone Disease, and as members of the Institute. Dr. Stewart, who has also been named Professor of Medicine (Endocrinology, Diabetes & Bone Diseases) will oversee the continued expansion of the Institute through the recruitment of additional researchers.
Dr. Stewart has devoted more than 30 years to patient care and scientific research, and received numerous honors, including the prestigious Aurbach award of The Endocrine Society, and also served as Program Chair for the American Diabetes Association Annual Scientific Sessions in 2010 and 2012. He has published more than 230 clinical and scientific papers in journals including the Proceedings of the National Academy of Sciences, The New England Journal of Medicine, and Science. He received his bachelor's degree from Trinity College in Hartford, Connecticut, and his MD from Columbia University, College of Physicians and Surgeons, in New York. He served as a fellow in Endocrinology and Metabolism and faculty member at Yale University School of Medicine in Connecticut, and later as Chief of the Division of Endocrinology at the University of Pittsburgh. Dr. Stewart currently has strong funding support from the National Institutes of Health, the Juvenile Diabetes Research Foundation, and other agencies.
Multi-Disciplinary Training AreasBiophysics and Systems Pharmacology [BSP], Developmental and Stem Cell Biology [DSCB], Genetics and Genomic Sciences [GGS]
MD, Columbia University, College of Physicians and Surgeons
Dr. Andrew Stewart is the Scientific Director of the Diabetes, Obesity and Metabolism Institute (DOMI). He an authority on human insulin-producing pancreatic beta cell replication and regeneration for people with diabetes. His research focuses on understanding and developing novel therapies for inducing human beta cell regeneration, from gene therapy to small molecule drug discovery. His group was the first to demonstrate that growth factors could drive beta cell replication in vivo in mammals, and also improve glucose control in living animals. His group was also the first to carefully define cell cycle control in the rodent and human beta cell. They were also the first to report that small molecule drugs that inhibit the enzyme DYRK1A are able to induce human beta cells to replicate, and to reverse diabetes in vivo in mice transplanted with human beta cells. He is actively involved in developing next-generation DYRK1A inhibitors for human diabetes, and understanding why human beta cells are so refractory to replication. His work has been continually supported by the NIH/NIDDK and the JDRF.
Please visit the Stewart Laboratory.
Cozar-Castellano I, Weinstock M, Haught M, Velázquez-Garcia S, Sipula D, Stewart AF. Evaluation of beta-cell replication in mice transgenic for hepatocyte growth factor and placental lactogen: comprehensive characterization of the G1/S regulatory proteins reveals unique involvement of p21cip. Diabetes 2006 Jan; 55(1).
Horwitz MJ, Tedesco MB, Sereika SM, Garcia-Ocaña A, Bisello A, Hollis BW, Gundberg C, Stewart AF. Safety and tolerability of subcutaneous PTHrP(1-36) in healthy human volunteers: a dose escalation study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2006 Feb; 17(2).
Siminerio LM, Piatt GA, Emerson S, Ruppert K, Saul M, Solano F, Stewart A, Zgibor JC. Deploying the chronic care model to implement and sustain diabetes self-management training programs. The Diabetes educator; 32(2).
Fiaschi-Taesch N, Sicari BM, Ubriani K, Bigatel T, Takane KK, Cozar-Castellano I, Bisello A, Law B, Stewart AF. Cellular mechanism through which parathyroid hormone-related protein induces proliferation in arterial smooth muscle cells: definition of an arterial smooth muscle PTHrP/p27kip1 pathway. Circulation research 2006 Oct; 99(9).
Kelly TG, Shattuck TM, Reyes-Mugica M, Stewart AF, Simonds WF, Udelsman R, Arnold A, Carpenter TO. Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2006 Oct; 21(10).
Cozar-Castellano I, Haught M, Stewart AF. The cell cycle inhibitory protein p21cip is not essential for maintaining beta-cell cycle arrest or beta-cell function in vivo. Diabetes 2006 Dec; 55(12).
Zgibor JC, Orchard TJ, Saul M, Piatt G, Ruppert K, Stewart A, Siminerio LM. Developing and validating a diabetes database in a large health system. Diabetes research and clinical practice 2007 Mar; 75(3).
Vasavada RC, Cozar-Castellano I, Sipula D, Stewart AF. Tissue-specific deletion of the retinoblastoma protein in the pancreatic beta-cell has limited effects on beta-cell replication, mass, and function. Diabetes 2007 Jan; 56(1).
Cozar-Castellano I, Harb G, Selk K, Takane K, Vasavada R, Sicari B, Law B, Zhang P, Scott DK, Fiaschi-Taesch N, Stewart AF. Lessons from the first comprehensive molecular characterization of cell cycle control in rodent insulinoma cell lines. Diabetes 2008 Nov; 57(11).
Wesseling-Perry K, Harkins GC, Wang HJ, Elashoff R, Gales B, Horwitz MJ, Stewart AF, Jüppner H, Salusky IB. The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84). The Journal of clinical endocrinology and metabolism 2010 Jun; 95(6).
Carneiro RM, Prebehalla L, Tedesco MB, Sereika SM, Hugo M, Hollis BW, Gundberg CM, Stewart AF, Horwitz MJ. Lactation and bone turnover: a conundrum of marked bone loss in the setting of coupled bone turnover. The Journal of clinical endocrinology and metabolism 2010 Apr; 95(4).
Harb G, Vasavada RC, Cobrinik D, Stewart AF. The retinoblastoma protein and its homolog p130 regulate the G1/S transition in pancreatic beta-cells. Diabetes 2009 Aug; 58(8).
Fiaschi-Taesch N, Bigatel TA, Sicari B, Takane KK, Salim F, Velazquez-Garcia S, Harb G, Selk K, Cozar-Castellano I, Stewart AF. Survey of the human pancreatic beta-cell G1/S proteome reveals a potential therapeutic role for cdk-6 and cyclin D1 in enhancing human beta-cell replication and function in vivo. Diabetes 2009 Apr; 58(4).
Guthalu Kondegowda N, Joshi-Gokhale S, Harb G, Williams K, Zhang XY, Takane KK, Zhang P, Scott DK, Stewart AF, Garcia-Ocaña A, Vasavada RC. Parathyroid hormone-related protein enhances human ß-cell proliferation and function with associated induction of cyclin-dependent kinase 2 and cyclin E expression. Diabetes 2010 Dec; 59(12).
Fiaschi-Taesch N, Sicari B, Ubriani K, Cozar-Castellano I, Takane KK, Stewart AF. Mutant parathyroid hormone-related protein, devoid of the nuclear localization signal, markedly inhibits arterial smooth muscle cell cycle and neointima formation by coordinate up-regulation of p15Ink4b and p27kip1. Endocrinology 2009 Mar; 150(3).
Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforova MN. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. The Journal of clinical endocrinology and metabolism 2011 Nov; 96(11).
Niemeier LA, Kuffner Akatsu H, Song C, Carty SE, Hodak SP, Yip L, Ferris RL, Tseng GC, Seethala RR, Lebeau SO, Stang MT, Coyne C, Johnson JT, Stewart AF, Nikiforov YE. A combined molecular-pathologic score improves risk stratification of thyroid papillary microcarcinoma. Cancer 2012 Apr; 118(8).
Williams K, Abanquah D, Joshi-Gokhale S, Otero A, Lin H, Guthalu NK, Zhang X, Mozar A, Bisello A, Stewart AF, Garcia-Ocaña A, Vasavada RC. Systemic and acute administration of parathyroid hormone-related peptide(1-36) stimulates endogenous beta cell proliferation while preserving function in adult mice. Diabetologia 2011 Nov; 54(11).
Horwitz MJ, Tedesco MB, Sereika SM, Prebehala L, Gundberg CM, Hollis BW, Bisello A, Garcia-Ocaña A, Carneiro RM, Stewart AF. A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2011 Sep; 26(9).
Levitt HE, Cyphert TJ, Pascoe JL, Hollern DA, Abraham N, Lundell RJ, Rosa T, Romano LC, Zou B, O'Donnell CP, Stewart AF, Garcia-Ocaña A, Alonso LC. Glucose stimulates human beta cell replication in vivo in islets transplanted into NOD-severe combined immunodeficiency (SCID) mice. Diabetologia 2011 Mar; 54(3).
Mellado-Gil J, Rosa TC, Demirci C, Gonzalez-Pertusa JA, Velazquez-Garcia S, Ernst S, Valle S, Vasavada RC, Stewart AF, Alonso LC, Garcia-Ocaña A. Disruption of hepatocyte growth factor/c-Met signaling enhances pancreatic beta-cell death and accelerates the onset of diabetes. Diabetes 2011 Feb; 60(2).
Christopher LJ, Hong H, Vakkalagadda BJ, Clemens PL, Su H, Roongta V, Allentoff A, Sun H, Heller K, Harbison CT, Iyer RA, Humphreys WG, Wong T, Zhang S. Metabolism and disposition of [14C]BMS-690514, an ErbB/vascular endothelial growth factor receptor inhibitor, after oral administration to humans. Drug metabolism and disposition: the biological fate of chemicals 2010 Nov; 38(11).
Kulkarni RN, Mizrachi EB, Ocana AG, Stewart AF. Human β-cell proliferation and intracellular signaling: driving in the dark without a road map. Diabetes 2012 Sep; 61(9).
Metukuri MR, Zhang P, Basantani MK, Chin C, Stamateris RE, Alonso LC, Takane KK, Gramignoli R, Strom SC, O'Doherty RM, Stewart AF, Vasavada RC, Garcia-Ocaña A, Scott DK. ChREBP mediates glucose-stimulated pancreatic β-cell proliferation. Diabetes 2012 Aug; 61(8).
Takane KK, Kleinberger JW, Salim FG, Fiaschi-Taesch NM, Stewart AF. Regulated and reversible induction of adult human β-cell replication. Diabetes 2012 Feb; 61(2).
Walpita D, Hasaka T, Spoonamore J, Vetere A, Takane KK, Fomina-Yadlin D, Fiaschi-Taesch N, Shamji A, Clemons PA, Stewart AF, Schreiber SL, Wagner BK. A human islet cell culture system for high-throughput screening. Journal of biomolecular screening 2012 Apr; 17(4).
Toledo FG, Stewart AF. The academic and clinical endocrinology physician workforce in the U.S. The Journal of clinical endocrinology and metabolism 2011 Apr; 96(4).
Karslioglu E, Kleinberger JW, Salim FG, Cox AE, Takane KK, Scott DK, Stewart AF. cMyc is a principal upstream driver of beta-cell proliferation in rat insulinoma cell lines and is an effective mediator of human beta-cell replication. Molecular endocrinology (Baltimore, Md.) 2011 Oct; 25(10).
Fiaschi-Taesch N, Stewart AF, Garcia-Ocaña A. Improving islet transplantation by gene delivery of hepatocyte growth factor (HGF) and its downstream target, protein kinase B (PKB)/Akt. Cell biochemistry and biophysics 2007; 48(2-3).
Cozar-Castellano I, Fiaschi-Taesch N, Bigatel TA, Takane KK, Garcia-Ocaña A, Vasavada R, Stewart AF. Molecular control of cell cycle progression in the pancreatic beta-cell. Endocrine reviews 2006 Jun; 27(4).
Horwitz MJ, Stewart AF. Hypoparathyroidism: is it time for replacement therapy?. The Journal of clinical endocrinology and metabolism 2008 Sep; 93(9).
Fiaschi-Taesch NM, Kleinberger JW, Salim F, Troxell R, Wills R, Tanwir M, Casinelli G, Cox AE, Takane KK, Srinivas H, Scott DK, Stewart AF. Cytoplasmic-Nuclear Trafficking of G1/S Cell Cycle Molecules and Adult Human Beta Cell Replication: A Revised Model of Human Beta Cell G1/S Control. Diabetes 2013 Mar;.
Fiaschi-Taesch NM, Kleinberger JW, Salim F, Troxell R, Wills R, Tanwir M, Casinelli G, Cox AE, Takane KK, Scott DK, Stewart AF. A Human Pancreatic Beta Cell G1/S Molecule Cell Cycle Atlas. Diabetes 2013 Mar;.