Jennifer Moss, PhD

Faculty Member, Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center

Position

Assistant Professor Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition Duke University Medical Center

Contact

Carmichael Building

919 479 2379

jennifer.b.moss@duke.edu

Summary

Jennifer Moss, PhD has been a member of the Duke University Medical Center and the Sarah W. Stedman Center since 2005. She is an Assistant Professor of Medicine in the Division of Endocrinology, Metabolism, and Nutrition. Dr. Jennifer Moss' training in developmental biology and organogenesis has been focused on the establishment and evaluation of new models that produce insights into human cardiac and pancreatic disease. Through the use of the zebrafish as a whole animal system, the Moss lab has found that islet tissue can be regenerated after conditional genetic, chemical or surgical ablation without the need for insulin therapy. Regenerating, transparent zebrafish are currently being used to evaluate the activity of small molecules on the potentiation of beta cell neogenesis and beta cell function in vivo. By translating positive hits into mammalian islets and engineered tissues, we are developing a pipeline to identify potential drugs for biomedical diabetes therapies. Interests: 

  • Small molecule potentiation of beta cell regeneration
  • In vivo analysis of signal transduction pathways in the islet.
  • Pancreatic islet regeneration and stem cell biology in vertebrate model systems.
  • Vertebrate developmental biology and pancreas organogenesis
  • Imaging and image analysis of islet cells and islet vasculature

BA, SUNY Binghamton, Binghamton, NY
PhD, Baylor College of Medicine, Houston, TX Fellowship, CVRC, Harvard Medical School, Massachusetts General Hospital-East, Charlestown, MA

The Moss laboratory is focused on understanding how pancreatic beta cell neogenesis and function can be potentiated in vivo using zebrafish and other animal models of beta cell regeneration in adults. Our experiments are ultimately directed towards providing translational information that can be used as diabetes therapeutics in humans. Previous analysis of mammalian insulin (1,2) and cardiac actin (3) promoters in cell lines has led to our development of in vivo models where relevant changes in gene expression or cell signaling represent physiological changes (4). Although developmental paradigms can instruct organogenesis and metabolism (5,6), we have redirected our focus on generating adult models of diabetes and obesity (7,8). We have found that islet tissue can be regenerated after conditional genetic, chemical or surgical ablation without the need for insulin therapy in living adult zebrafish (8). Using transparent, conditional knock-out adults as a platform for small molecule manipulation of important signaling pathways in the beta cell, we are discovering critical signal transduction nodes necessary for regeneration. This economical and efficient zebrafish model, where beta cells can be evaluated directly in the same animal over time using fluorescent markers, provides a framework for understanding how small molecules affect beta cell growth and function in vivo. Interestingly, an unexpected source of auto-fluorescence in zebrafish provides a cautionary tale for researchers using whole animal models (9). Recently, we have expanded our inquiry into beta cell regeneration by generating a dual reporter zebrafish where both beta cells and the islet microvasculature are labeled with fluorescent proteins (10). In vivo changes in both cell types are being evaluated in the presence of small molecule inhibitors or activators during regeneration.

Pancreatic beta cells are lost due to insulin resistance, inflammation, hyperglycemia or autoimmune attack and are not significantly replenished by endogenous progenitors in mammals. In contrast, we observe a robust regeneration of beta cells in contact with islet vasculature that restores function in adult zebrafish within two weeks (10). To determine if small molecules promoting beta cell regeneration in zebrafish might benefit humans, we are developing vascularized hydrogels to improve islet cell growth compared with conventional cultures. Cadaveric human islets are available for research, however their limited survival in culture after severance from pancreatic vasculature introduces significant errors in evaluating experimental outcomes from multiple donors. In contrast, vascularized hydrogels can sustain long-term culture of beta cells and when transplanted, rescue induced diabetes in rodent models more effectively than islets transplanted alone. In collaboration with Duke's Biomedical Engineering, small molecules potentiating regeneration in vivo are being used to test human islet tissue surrogates in vitro, directing new analysis and treatment paradigms for diabetes.

Please visit the Links page for recent discoveries.

Lab Members (Former and Present)
Owen Liu
Rebecca Schneider
Jacob Wood
Tanner Kaplan
Wei Wei Ye

Current Trainees
Jaehong Park PhD
Melanie Greenman MD (Duke Stead Fellow)
Lauren Rusy BA (Duke Biology)

Collaborators
Chris Newgard and team
Jennifer West and Laila Rudsari
David Tobin and Dana Sisk
Ken Poss and all the fish room scientists
John Rawls
Michel Bagnat
Virginia Kraus
Rochelle Schwartz-Bloom