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Research > Faculty Alphabetical > Michael McDaniel, PhD

Professor, Pathology and Immunology
Room 3709, West Building
Office: (314) 362-7435
Lab: (314) 362-7433
E-mail: mmcdaniel@wustl.edu
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Postdoctoral Training Program in Diabetes Research

Research

The focus of our laboratory is to define metabolic signaling pathways that mediate cell growth and proliferation in adult human and rodent pancreatic islets. Stimulating islet beta cells to proliferate is a clinical goal that could have a beneficial impact on both type 1 diabetes for ex vivo transplantation protocols and in type 2 diabetes for approaches that generate beta cell replication in vivo. Mammalian Target of Rapamycin (mTOR) is a protein kinase that integrates signals derived from growth factors and nutrients to regulate cell growth and proliferation. Our previous studies have demonstrated that nutrients stimulate mTOR-mediated DNA synthesis and cell cycle progression, prerequisite events for mitosis, in rodent islets but are rarely effective in human islets. Our recent findings have identified glycogen synthase kinase-3 (GSK-3) as a key component in the regulation of mTOR-dependent regenerative processes. Remarkably, the GSK-3 inhibitors such as lithium or the highly specific 1-azakenpaullone, possess the unique ability to stimulate mTOR-dependent DNA synthesis, cell cycle progression and an increase in proliferation markers, Ki-67 and BrdU incorporation, in human beta cells. Our ongoing studies will utilize molecular and genetic approaches to understand the transcriptional and translational signals that facilitate GSK-3 and mTOR-mediated regenerative processes necessary to expand functional human beta cells.

Editorial Responsibilities

2001 - 2004Editorial BoardDiabetes
2001 - 2004Associate EditorAmerican Journal of Physiology - Endocrinology and Metabolism
1998 - 2001MemberVA Merit Review Committee - Endocrinology
1997 - 2001MemberAmerican Diabetes Grant Review Committee
1997 - 2001Editorial BoardEndocrinology
1995 - 2001Editorial BoardAmerican Journal of Physiology - Endocrinology and Metabolism
1992 - 1996Associate EditorDiabetes
1988 - 1991Editorial BoardDiabetes
1988 - 1992MemberNIH Metabolism Study Section

Service to the Department

1990 - PresentProgram Director NIH Institutional National Research Service Award (Postdoctoral Training Grant), "Cell Biologic Approaches to Diabetes Research"

Service to the University

2009 - PresentCore Director, DRTC Morphology & BioImaging Core, Islet Cell Subcore Director
2005 - 2009Member Medical School Commitee on Admissions
PresentMedical School Representative to the Faculty of Arts and Sciences

DBBS Graduate Program Affiliation

Molecular Cell Biology Program

Selected Publications

Rohatgi N, Remedi MS, Kwon G, Pappan KL, Marshall CA, McDaniel ML. Therapeutic strategies to increase human beta cell growth and proliferation by regulating mTOR and GSK-3/beta-catenin pathways. The Open Endocrinol J 4:42-56, 2010

Chakravarthy MV, Zhu Y, Yin L, Coleman T, Pappan KL, Marshall CA, McDaniel ML, Semenkovich CF. Inactivation of hypothalamic fatty acid synthase protects mice from diet-induced obesity and inflammation. J Lipid Res 50:630-640, 2009 Abstract

Liu H, Remedi MS, Pappan KL, Kwon G, Rohatgi N, Marshall CA, McDaniel ML. Glycogen synthase kinase-3 (GSK-3) and mammalian target of rapamycin (mTOR) pathways contribute to DNA synthesis, cell cycle progression and proliferation in human islets. Diabetes 58:663-672, 2009 Abstract

Chakravarthy MV, Zhu Y, Wice MB, Coleman T, Pappan KL, Marshall CA, McDaniel ML, Semenkovich CF. Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age. Diabetes 57:2698-2707, 2008 Abstract

Kwon G, Marshall CA, Liu H, Pappan KL, Remedi MS, McDaniel ML. Glucose-stimulated DNA synthesis through mammalian target of rapamycin (mTOR) is regulated by KATP channels. J Biol Chem 281:3261-3267, 2006 Abstract

Remedi MS, Rocheleau JV, Tong A, Patton BL, McDaniel ML, Piston DW, Koster JC, NIchols CG. Hyperinsulinism in mice with heterozygous loss of K(ATP) channels. Diabetologia 49:2368-2378, 2006 Abstract

Marshall CA, McDaniel ML. Regulation of mTOR in adult pancreatic islets-revisited. Commentaries on Perspectives in Diabetes, Vol 3, RP Robertson, ed, 2006

Pappan KL, Pan Z, Kwon G, Marshall CA, Coleman T, Goldberg IJ, McDaniel ML, Semenkovich CF. Pancreatic beta-cell lipoprotein lipase independently regulates islet glucose metabolism and normal insulin secretion. J Biol Chem 280:9023-9029, 2005 Abstract

Remedi M, Koster JC, Markova K, Seino S, Miki T, Patton BL, McDaniel ML, NIchols CG. Diet-induced glucose intolerance in mice with decreased beta-cell ATP-sensitive K+ channels. Diabetes 53:3159-3167, 2004 Abstract

Kwon G, Marshall CA, Pappan KL, Remedi MS, McDaniel ML. Signaling elements involved in the metabolic regulation of mTOR by nutrients, incretins and growth factors in islets. Diabetes (Suppl) 3:S225-232, 2004 Abstract

Kwon G, Pappan KL, Marshall CA, Schaffer JE, McDaniel ML. Cyclic AMP dose-dependently prevents palmitate-induced apoptosis by both PKA- and cAMP-GEF-dependent pathways in beta-cells. J Biol Chem 279:8938-8945, 2004 Abstract

Kwon G, Xu G, Cruz WS, Marshall CA, McDaniel ML. Autoregulation of protein synthesis by translation. In "RNA Binding Proteins: New Concepts in Gene Regulation". Eds. Kathryn Sandberg and Susan E. Mulroney, Kluwer Academic Publishers, Boston, pp 71-86, 2002

McDaniel ML, Marshall CA, Pappan KL, Kwon G. Metabolic and autocrine regulation of the mammalian target of rapamycin by pancreatic beta-cells. Diabetes 51:2877-2885, 2002 Abstract

Greenberg AS, McDaniel ML. Identifying the links between obesity, insulin resistance and beta-cell function: potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes. Eur J Clin Invest 32(Suppl3):24-34, 2002 Abstract

Greiwe JS, Kwon G, McDaniel ML, Semenkovich CF. Leucine and insulin activate p70S6 kinase through different pathways in human skeletal muscle. Am J Physiol Endocrinol Metab 281:E466-E471, 2001 Abstract

Cruz WS, Kwon G, Marshall CA, McDaniel ML, Semenkovich CF. Glucose and insulin stimulate heparin-releasable lipoprotein lipase activity in mouse islets and INS-1 cells. J Biol Chem 276:12162-12168, 2001 Abstract

Xu G., Kwon G, Cruz WS, Marshall CA, McDaniel ML. Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic beta-cells. Diabetes 50:353-360, 2001 Abstract

Marshall BA, Tordjman K, Host HH, Ensor NJ, Kwon G, Marshall CA, Coleman T, McDaniel ML, Semenkovich. Relative hypoglycemia and hyperinsulinemia in mice with heterozygous lipoprotein lipase (LPL) deficiency. Islet LPL regulates insulin secretion. J Biol Chem 274:27426-27432, 1999 Abstract

Kwon G, Xu G, Marshall CA, McDaniel ML. Tumor necrosis factor a-induced pancreatic beta-cell insulin resistance is mediated by nitric oxide and prevented by 15-deoxy-D12,14-prostaglandin J2 and aminoguanidine. J Biol Chem 274:18702-18708, 1999 Abstract

Xu G, Kwon G, Marshall CA, Lin T-A, Lawrence JC Jr, McDaniel ML. Branched-chain amino acids are essential in the regulation of PHAS-I and p70S6 kinase by pancreatic beta-cells: a possible role in protein translation and mitogenic signaling. J Biol Chem 273:28178-28184, 1998 Abstract

Xu G, Marshall CA, Lin TA, Kwon G, Munivenkatappa RB, Lawrence JC Jr, McDaniel ML. Insulin mediates glucose stimulated phosphorylation of PHAS-I by pancreatic beta-cells: an insulin-receptor mechanism for autoregulation of protein translation. J Biol Chem 273:4485-4491, 1998 Abstract

Kwon G, Corbett JA, Hauser S, Hill JR, Turk J, McDaniel ML. Evidence for involvement of the proteasome complex (26S) in IL-1-induced nitric oxide and prostaglandin production by rat islet and RINm5F cells. Diabetes 47:583-591, 1998 Abstract

Hill JR, Kwon G, Marshall CA, McDaniel ML. Hyperglycemic levels of glucose inhibit interleukin 1 release from RAW 264.7 murine macrophages by activation of protein kinase C. J Biol Chem 273:3308-3313, 1998 Abstract

Kwon G, Hill JR, Corbett JA, McDaniel ML. Effects of aspirin on NO formation and de novo protein synthesis by RINm5F cell and rat islets. Mol Pharmacol 52:398-405, 1997 Abstract

Scarim AL, Arnush M, Hill JR, Marshall CA, Baldwin A, McDaniel ML, Corbett JA. Evidence for the presence of type 1 IL-1 receptors on "b"-cells of islets of Langerhans. Biochim Biophys Acta 1361:313-320, 1997 Abstract

Hill JR, Corbett JA, Kwon G, Marshall CA, McDaniel ML. Nitric oxide regulates interleukin 1 bioactivity released from murine macrophages. J Biol Chem 271:22672-22678, 1996 Abstract

Zhao W, Tilton RG, Corbett JA, McDaniel ML, Misko TP, Williamson JR, Cross AH, Hickey WF. Experimental allergic encephalomyelitis in the rat is inhibited by aminoguanidine, an inhibitor of nitric oxide synthase. J Neuroimmunol 64:123-133, 1996 Abstract

Hill JR, Corbett JA, Baldwin AC, McDaniel ML. Nitric oxide production by the rat insulinoma cell line, RINm5F, is specific for IL-1: a spectometric IL-1 bioassay. Anal Biochem 236:14-19, 1996 Abstract

Corbett JA, Kwon G, Marino MH, Rodi CP, Sullivan PM, Turk J, McDaniel ML. Tyrosine kinase inhibitors prevent cytokine-induced expression of iNOS and COX-2 by human islets of Langerhans. Am J Physiol 270:C1581-C1587, 1996 Abstract


Current Trainees

Haytham Aly, PhD
Nidhi Rohatgi, PhD

Past Trainees

Maria Remedi, PhD
Postdoctoral Fellows
Hui Liu, PhD
Kirk Pappan, PhD