faculty photo

Doris A. Stoffers

Sylvan H. Eisman Professor of Medicine
Department: Medicine

Contact information
Smilow Center for Translational Research, Room 12-124
3400 Civic Center Boulevard
Philadelphia, PA 19104
Office: 215 573-5413
Fax: 215 898-5408
Graduate Group Affiliations
Education:
B.A. (Chemistry)
Johns Hopkins University , 1984.
Ph.D. (Neuroscience)
Johns Hopkins University, School of Medicine, 1991.
M.D.
Johns Hopkins University, School of Medicine, 1991.
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Description of Research Expertise

Research Interests
- transcription factors and signal transduction
- embryonic development and adult regeneration of the endocrine pancreas
- relationship of defects in these pathways to the pathophysiology of diabetes mellitus, a disease caused by a deficiency in the production or action of insulin

Key words: Diabetes, insulin, beta cell, pancreas development, transcriptional regulation, signal transduction.

Description of Research
Research in our laboratory focuses on the embryonic development and adult regeneration of the endocrine pancreas, and the relationship of defects in these pathways to the pathophysiology of diabetes mellitus, a disease caused by a deficiency in the production or action of insulin. The beta cells of the endocrine pancreas are the only source of insulin production in the body- therefore the regulation of beta cell mass is pivotal to the development of diabetes and successful therapies aimed at correcting diabetes must impact beta cell growth and/or function. Further support for this focus derives from genetic studies linking monogenic forms of human diabetes to mutations in transcription factors that regulate the development of beta cell mass. A model example is the homeobox transcription factor, IPF-1/PDX-1, that plays critical roles in embryonic pancreas development and in differentiated islet beta cell function in the adult endocrine pancreas. Using cutting edge molecular methods, yeast two hybrid libraries, transgenic and knock-out mice, cDNA microarray, chromatin immunoprecipitation, human genetics, and genomic and proteomic approaches, our current projects include:

1. Characterization of a novel PDX C-terminus Interacting Factor, PCIF1, identified in a yeast two-hybrid screen. PCIF1 is a novel nuclear factor that recruits Pdx1 into a cullin3 based E3 ubiquitin ligase for polyubiquitination and proteasomal degradation. Biochemical, molecular, in vivo and human genetics approaches are being applied to elucidate the role of this novel regulatory molecule.
2. Examining the molecular mechanisms by which the incretin hormone GLP-1 stimulates expansion of beta cell mass, with a particular emphasis on signal transduction and the identification of molecular mechanisms whereby GLP-1 promotes beta cell regeneration and regulates PDX expression.
3. Elucidating molecular mechanisms underlying islet compensation for diet-induced insulin resistance.
4. Identifing targets of Pdx1, Pbx and Meis homeodomain factors in the pancreatic ß cell.

Rotation Projects
Lab rotation projects are available in all of the major areas described above. Please arrange for an appointment to discuss.

Lab personnel:
Doris A. Stoffers, MD, PhD, Principal Investigator
Jiangying Liu, PhD Postdoctoral Fellow
Ada Po Man Suen, PhD Postdoctoral Fellow
Scott Soleimanpour, MD, Postdoctoral Fellow
You Wang, Postdoctoral Fellow
Jennifer Oliver-Krasinski, Graduate Student
Mira Sachdeva, Graduate Student
Katy Claiborn, Graduate Student
Cynthia Khoo, Graduate Student
David Groff, Research Specialist
Juxiang Yang, PhD, Research Specialist

Selected Publications

Henley K@, Stanescu D@, Kropp PA, Wright CVE, Won KJ, Stoffers DA*, Gannon M* *,@equal contribution: Threshold-dependent cooperative function of Pdx1 and Oc1 within pancreatic progenitors establishes competency for later β-cell maturation. Cell Reports 15(12): 2637-50, Jun 2016.

Melissa A. Burmeister, Jennifer E. Ayala, Hannah Smouse, Adriana LandivarRocha, Jacob D. Brown, Daniel J. Drucker, Doris A. Stoffers, Darleen A. Sandoval, Randy J. Seeley and Julio E. Ayala : The Hypothalamic Glucagon-Like Peptide-1 (GLP-1) Receptor (GLP-1R) is Sufficient but Not Necessary for the Regulation of Energy Balance and Glucose Homeostasis in Mice. Diabetes under review 2016.

Stanescu DE, Yu R, Won KJ, Stoffers DA: Single cell transcriptomic profiling of mouse pancreatic progenitors Physiological Genomics Accepted with minor revision 2016.

Daniella A. Babu, Andrea V. Rozo, PoMan A. Suen, David N. Groff, Juxiang Yang, Diana Stanescu, Rebecca A. Simmons, Patrick Seale, Rexford S. Ahima and Doris A. Stoffers: Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture. Cell Metabolism under review 2016.

Benjamin N. Ediger, Lim Hee-Woong, Christine Juliana, David Groff, LaQueena Williams, Giselle Dominguez, Jin-Hua Liu, Brandon Taylor, Erik Walp, Vasumathi Kamesawaran, Juxiang Yang, CHengyang Liu, Chad Hunter, Klaus Kaestnerm Ali Naji, Changhong Li, Maike Sander, Roland Stein, Lori Sussel, Kyoung Jae Won, Catherine Lee-May, Doris A. Stoffers: LIM-Domain-Binding 1 maintains the terminally-differentiated state of pancreatic β-cells. Journal of Clinical Investigation in press 2016.

Christine A. Juliana1, Juxiang Yang1, Andrea V. Rozo1, Austin Good1, David Groff1, Shu-Zong Wang2, Michael R. Green2 and Doris A. Stoffers1: ATF5 regulates β cell survival during stress Proceedings of the National Academy of Sciences USA under revision 2016.

Jarrett R. Remsberg1,2,3, Benjamin N. Ediger1,2, Wesley Y. Ho1,2, Manashree Damle1,2, Zhenghui Li1,2, Christopher Teng2, Cristina Lanzillotta1,2, Doris A. Stoffers1,2, and Mitchell A. Lazar1,2,4 : Deletion of Histone Deacetylase 3 in Adult Beta Cells Improves Glucose Tolerance via Increased Insulin Secretion Molecular Metabolism in press 2016.

Scott A. Soleimanpour; Alana M. Ferrari; Jeffrey C. Raum; David N. Groff; Juxiang Yang; Brett A. Kaufman; and Doris A. Stoffers: Diabetes susceptibility genes Pdx1 and Clec16a function in a pathway regulating mitophagy in β-cells Diabetes 64(10): 3475-84, October 2015.

Raum JC, Soleimanpour SA, Groff DN, Coré N, Fasano L, Garratt AN, Dai C, Powers AC, Stoffers DA: Tshz1 regulates pancreatic beta cell maturation. Diabetes 64(8): 2905-14, Aug 2015.

Wang A, Yue F, Li Y, Xie R, Harper T, Patel NA, Muth K, Palmer J, Qiu Y, Wang J, Lam DK, Raum JC, Stoffers DA, Ren B, Sander M: Epigenetic Priming of Enhancers Predicts Developmental Competence of hESC-Derived Endodermal Lineage Intermediates Cell Stem Cell 16(4): 386-99, 2015.

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Last updated: 11/17/2016
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