Doris A. Stoffers

faculty photo
Sylvan H. Eisman Professor of Medicine
Member, Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania
Member, Penn Diabetes Research Center, University of Pennsylvania
Member, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania
Director, Pilot and Feasibility Grant Program, Diabetes Research Center (DRC), University of Pennsylvania
Member Diabetes Research Center (DRC) Executive Committee, University of Pennsylvania
Director, Islet Cell Biology Core (Co-Director: Franz Matschinsky), Penn Diabetes Research Center Institute for Diabetes, Obesity and Metabolism Perelman School of Medicine at the University of Pennsylvania
Member, Burden Reduction Initiative, commissioned by the Vice Provost for Research Dawn Bonnell (Chair: Jon Vos)
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

Description of Itmat Expertise

The Stoffers laboratory studies the development, growth and regeneration of pancreatic beta cells, the source of insulin production that is critical to normal glucose homeostasis.

Selected Publications

Loyd C, Liu Y, Kim T, Holleman C, Galloway J, Bethea M, Ediger BN, Swain TA, Tang Y, Stoffers DA, Rowe GC, Young M, Steele C, Habegger KM, Hunter, CS : LDB1 Regulates Energy Homeostasis During Diet-Induced Obesity Endocrinology 158 (5): 1289-1297, May 2017

Remsberg JR, Ediger BN, Ho WY, Damle M, Li Z, Teng C, Lanzillotta C, Stoffers DA, and Lazar MA: Deletion of Histone Deacetylase 3 in Adult Beta Cells Improves Glucose Tolerance via Increased Insulin Secretion Molecular Metabolism 6(1): 30-37, Nov 2017.

Rozo AV, Babu DA, Suen PA, Groff DN, Seeley RJ, Simmons RA, Seale P, Ahima RS and Stoffers DA: Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture. Molecular Metabolism 6(7): 748-759, May 2017.

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 66(2): 372-384, Feb 2017.

Stanescu DE, Yu R, Won KJ, Stoffers DA: Single cell transcriptomic profiling of mouse pancreatic progenitors Physiological Genomics 49(2): 105-114, Feb 2017.

Juliana CA, Yang J, Rozo AV, Good A, Groff DN, Wang SZ, Green MR and Stoffers DA: ATF5 regulates β cell survival during stress Proceedings of the National Academy of Sciences USA 114(6): 1341-1346, Feb 2017.

Ediger BN, Hee-Woong L, Juliana CA, Groff DN, Williams L, Dominguez G, Liu JH, Taylor B, Walp E, Kamesawaran V, Yang J, Liu C, Hunter C, Kaestner KH, Naji A, Li C, Sander M, Stein R, Sussel L, Won KJ, May CS, Stoffers DA: LIM-Domain-Binding 1 maintains the terminally-differentiated state of pancreatic β-cells. Journal of Clinical Investigation 127(1): 215-229, Jan 2017.

Melissa Burmeister, Jacob Brown, Jennifer Ayala, Doris Stoffers, Darleen Sandoval, Randy Seeley, and Julio Ayala: The Glucagon-Like Peptide-1 Receptor in the Ventromedial Hypothalamus Reduces Short-Term Food Intake in Male Mice by Regulating Nutrient Sensor Activity. American Journal of Physiology in press 2017.

Peter Kropp, Jennifer Dunn, Bethany Carboneau, Doris Stoffers, and Maureen Gannon : Cooperative function of Pdx1 and Oc1 in multipotent pancreatic progenitors impacts postnatal islet maturation and adaptability. American Journal of Physiology-Endocrinology and Metabolism under review 2017.

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.

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Last updated: 09/13/2017
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