Donald Scott, PhD
- Professor of Medicine (Endocrinology, Diabetes and Bone Disease)
Research Topics:Cancer, Cell Biology, Cell Cycle, Chromatin, Diabetes, Epigenetics, Gene Expressions, Gene Regulation, Gene Therapy, Growth Factors and Receptors, Hormones, Image Analysis, Imaging, Insulin, Insulin Receptor, Knockout Mice, Liver, Molecular Biology, Nucleus, Obesity, Oncogenes, Protein Kinases, RNA, RNA Splicing & Processing, Transcription Factors, Transcriptional Activation and Repression, Transgenic Mice
Dr. Scott’s group works on the nutritional regulation of cellular phenotype. His lab works on molecular mechanisms that coordinate how nutrients, especially glucose, alter the regulation of genes to change the phenotype of cells. His work focuses on two glucose-sensing transcription factors, ChREBP and c-Myc. He found that ChREBP activity requires the presence of c-Myc and is currently working out the molecular mechanisms of this relationship. In addition, his lab, in collaboration with colleagues from the Metabolism Institute (Drs. Garcia-Ocaña, Vasavada, and Stewart) found that ChREBP is required for glucose-stimulated beta cell proliferation. This work is funded by the NIH, the American Diabetes Association, and the Juvenile Diabetes Research Foundation.Dr. Scott is member of the Graduate Faculty and is affiliated with the Systems Biology of Disease and Therapeutics Multiple Training Area.
Multi-Disciplinary Training AreaBiophysics and Systems Pharmacology [BSP]
AB, University of Missouri
MA, University of Missouri
PhD, Saint Louis University
Collier JJ, Doan TT, Daniels MC, Schurr JR, Kolls JK, Scott DK. c-Myc is required for the glucose-mediated induction of metabolic enzyme genes. The Journal of biological chemistry 2003 Feb; 278(8).
Collier JJ, Scott DK. Sweet changes: glucose homeostasis can be altered by manipulating genes controlling hepatic glucose metabolism. Molecular endocrinology (Baltimore, Md.) 2004 May; 18(5).
Collier JJ, Zhang P, Pedersen KB, Burke SJ, Haycock JW, Scott DK. c-Myc and ChREBP regulate glucose-mediated expression of the L-type pyruvate kinase gene in INS-1-derived 832/13 cells. American journal of physiology. Endocrinology and metabolism 2007 Jul; 293(1).
Alonso LC, Yokoe T, Zhang P, Scott DK, Kim SK, O'Donnell CP, Garcia-Ocaña A. Glucose infusion in mice: a new model to induce beta-cell replication. Diabetes 2007 Jul; 56(7).
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).
Burke SJ, Collier JJ, Scott DK. cAMP opposes the glucose-mediated induction of the L-PK gene by preventing the recruitment of a complex containing ChREBP, HNF4alpha, and CBP. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2009 Sep; 23(9).
Graves JA, Metukuri M, Scott D, Rothermund K, Prochownik EV. Regulation of reactive oxygen species homeostasis by peroxiredoxins and c-Myc. The Journal of biological chemistry 2009 Mar; 284(10).
Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O'Doherty RM. Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes 2010 Feb; 59(2).
Fiaschi-Taesch NM, Salim F, Kleinberger J, Troxell R, Cozar-Castellano I, Selk K, Cherok E, Takane KK, Scott DK, Stewart AF. Induction of human beta-cell proliferation and engraftment using a single G1/S regulatory molecule, cdk6. Diabetes 2010 Aug; 59(8).
Zhang P, Metukuri MR, Bindom SM, Prochownik EV, O'Doherty RM, Scott DK. c-Myc is required for the CHREBP-dependent activation of glucose-responsive genes. Molecular endocrinology (Baltimore, Md.) 2010 Jun; 24(6).
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).
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).
Velazquez-Garcia S, Valle S, Rosa TC, Takane KK, Demirci C, Alvarez-Perez JC, Mellado-Gil JM, Ernst S, Scott DK, Vasavada RC, Alonso LC, Garcia-Ocaña A. Activation of protein kinase C-ζ in pancreatic β-cells in vivo improves glucose tolerance and induces β-cell expansion via mTOR activation. Diabetes 2011 Oct; 60(10).
Stefanovic-Racic M, Yang X, Turner MS, Mantell BS, Stolz DB, Sumpter TL, Sipula IJ, Dedousis N, Scott DK, Morel PA, Thomson AW, O'Doherty RM. Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes 2012 Sep; 61(9).
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;.
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;.
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).
Wang P, Fiaschi-Taesch NM, Vasavada RC, Scott DK, García-Ocaña A, Stewart AF. Diabetes mellitus-advances and challenges in human β-cell proliferation. Nature reviews. Endocrinology 2015 Feb;.
Wang P, Alvarez-Perez JC, Felsenfeld DP, Liu H, Sivendran S, Bender A, Kumar A, Sanchez R, Scott DK, Garcia-Ocaña A, Stewart AF. A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. Nature medicine 2015 Mar;.
Zhang P, Kumar A, Katz LS, Li L, Paulynice M, Herman MA, Scott DK. Induction of the ChREBPβ isoform is essential for glucose-stimulated beta cell proliferation. Diabetes 2015 Sep;.
Martins FO, Delgado TC, Viegas J, Gaspar J, Scott DK, O'Doherty RM, Macedo MP, Jones JG. Mechanisms by which the thiazolidinedione troglitazone protects against sucrose-induced hepatic fat accumulation and hyperinsulinemia. British journal of pharmacology 2015 Oct;.
Lakshmipathi J, Alvarez-Perez JC, Rosselot C, Casinelli GP, Stamateris RE, Rausell-Palamos F, O'Donnell CP, Vasavada RC, Scott DK, Alonso LC, Garcia-Ocaña A. PKC-ζ is essential for pancreatic beta cell replication during insulin resistance by regulating mTOR and cyclin-D2. Diabetes 2016 Feb;.