Suparna Sarkar MBBS, PhD
Instructor, Barbara Davis Center
DERC Bioinformatics Core Director, The Diabetes and Endocrinology Research Center (DERC)
BioSketch
The focus of my research is two-fold:
1) To understand how T cells secreted soluble mediators like cytokines: IL1b, TNF-a, IFN-g and chemokines impair beta cell function and subsequently cause beta cell destruction. We investigate global changes in gene expression and pathways modulated in cultured human islets exposed to cytokines. Our aim is to understand the molecular mechanism of cytokine -induced cell death and infer mechanisms to prevent beta cell death.
2) Our other approach is to understand the origin and life cycle of b-cells in humans. Our current knowledge of transcriptional regulation of mammalian pancreatic development are largely derived from extrapolation of studies on mice and other models of development in which gene regulation can be manipulated in a conditional and tissue specific manner to provide information on signaling pathways and cell lineage. Although the morphogenesis of the endocrine tissue is unlikely to be equivalent in human and mouse, given the differences in gestation and the larger relative volume of the human pancreas (high resolution images of human fetal pancreas 9-23 weeks of gestation are available through this link), we believe that by drawing parallels with rodents and other models of development, we can derive unique data regarding islet precursor-cell population that could be expanded ex vivo for therapeutic transplantation in human subjects. Elucidation of molecular factors that are responsible for the development and function of ß-cells in humans is key to generating new research tools that will provide critical insights into the prevention and treatment of diabetes. Our current and future research endeavors are directed towards finding answers to these exciting questions.
Publications:
Pound LD, Sarkar S, Benninger RK, Wang Y, Suwanichkul A, Shadoan MK, Printz RL, Oeser JK, Lee CE, Piston DW, McGuinness OP, Hutton JC, Powell DR, O'Brien RM (2009). Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion. Biochem J. [Epub ahead of print]
Sarkar SA, Kutlu B, Velmurugan K, Kizaka-Kondoh S, Lee CE, Wong R, Valentine A, Davidson HW, Hutton JC, Pugazhenthi S (2009). Cytokine-mediated induction of anti-apoptotic genes that are linked to nuclear factor kappa-B (NF-kappaB) signalling in human islets and in a mouse beta cell line. Diabetologia. 52 (6):1092-1101.
Wolter T, Wong R, Sarkar SA, Zipris D (2009). DNA microarray analysis for the identification of innate immune pathways implicated in virus-induced autoimmune diabetes. Clinical Immunology Mar 25 [Epub ahead of print].
Wenzlau JM, Frisch LM, Gardner TJ, Sarkar S, Hutton JC, Davidson HW (2009). Novel antigens in type 1 diabetes: the importance of ZnT8. Curr Diab Rep. 9(2):105-112.
Wenzlau JM, Moua O, Sarkar SA, Yu L, Rewers M, Eisenbarth GS, Davidson HW, Hutton JC (2008). SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes. Ann N Y Acad Sci. 1150:256-259
Quayum N, Kutchma A, Sarkar SA, Juhl K, Gradwohl G, Mellitzer G, Hutton JC, Jensen J (2008). GeneSpeed Beta Cell: an online genomics data repository and analysis resource tailored for the islet cell biologist. Exp Diabetes Res, 2008:312060.
Juhl K, Sarkar SA, Wong R, Jensen J, Hutton JC (2008). Definition of the mouse pancreatic islet transcriptome. Diabetes, 57(10): 2755-2761.
Sarkar SA, Kobberup S, Wong R, Lopez AD, Quayum N, Still T, Kutchma A, Jensen JN, Gianani R, Beattie GM, Jensen J, Hayek A, Hutton JC (2008). Global gene expression profiling and histochemical analysis of the developing human fetal pancreas. Diabetologia 51(2):285-97.
Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J, Davidson HW, Hutton JC. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes (2007). Proc Natl Acad Sci U S A. 104(43):17040-5.
Sarkar SA, Gunter J, Bouchard R, Reusch JE, Wiseman A, Gill RG, Hutton JC, Pugazhenthi S (2007). Dominant negative mutant forms of the cAMP response element binding protein induce apoptosis and decrease the anti-apoptotic action of growth factors in human islets. Diabetologia. 50(8):1649-59.
Wang Y, Martin CC, Oeser JK, Sarkar S, McGuinness OP, Hutton JC, O'Brien RM (2007). Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype. Diabetologia. 50(4):774-8.
Sarkar SA, Wong R, Hackl SI, Moua O, Gill RG, Wiseman A, Davidson HW, Hutton JC (2007). Induction of indoleamine 2,3-dioxygenase by interferon-gamma in human islets. Diabetes. 56(1):72-9.
Wang Y, Oeser JK, Yang C, Sarkar S, Hackl SI, Hasty AH, McGuinness OP, Paradee W, Hutton JC, Powell DR, O'Brien RM (2006). Deletion of the gene encoding the ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein (UGRP)/glucose-6-phosphatase catalytic subunit-beta results in lowered plasma cholesterol and elevated glucagon. J Biol Chem. 281(52):39982-9.
Sarkar SA and Sharma RP (2003). Modulation of p53 after maternal exposure to all-trans-retinoic-acid in Swiss Webster mouse fetuses, Experimental and Molecular Pathology, 74(3), 298-308.
Sarkar SA and Sharma RP (2002). Expression of selected apoptosis related genes, MIF, IGIF and TNF alpha, during retinoic acid-induced neural differentiation in murine embryonic stem cells. Cell Structure and Function, 27, 99-107.
Sarkar SA and Sharma RP (2002). Modulation of c-Myc, max, and mad gene expression during neural differentiation of murine embryonic stem cells by all-trans-retinoic acid. Gene Expression, 10(3), 125-135.
Sarkar SA and Sharma RP (2002). Expression of c-Myc and other apoptosis-related genes in swiss webster mice fetuses after maternal exposure to all trans-retinoic acid, Reproductive Toxicology, 16(3), 245-252.
Sarkar SA and Sharma RP (2002). All-trans-retinoic acid-mediated modulation of p53 during neural differentiation in murine embryonic stem cells. Cell Biology and Toxicology, 18(4), 243-257.
To access a more complete listing of publications, please go to PubMed http://www.ncbi.nlm.nih.gov/PubMed/ and use the search term Barbara Davis Center for Childhood Diabetesor enter individual author names.
Please direct inquiries to specific e-mail addresses listed within individual entries. For all other general Research inquiries, please contact:
kathryn.gray@ucdenver.edu