Until recently, little detailed information was known about the factors controlling pancreas development and islet alpha and beta cell function. However, our understanding has increased greatly with the identification and molecular characterization of islet-enriched transcription factors like MAFA, MAFB, and PDX-1. Gene knockouts performed on these in human embryonic stem cells and islets are elucidating how each influence pancreatic morphogenesis and adult islet cell function. Because of their fundamental significance to alpha and beta cells, work here is also focused on identifying the coregulators recruited by MAFA, MAFB, and PDX1 mediate transcriptional control in human islets. Animal, human islet, and cell culture systems are used in our studies, with comprehensive and diverse methods from CRISPR/Cas9, islet cell transplantation to mass spectrometry involved in addressing our experimental questions.
Understanding the mechanisms involved in controlling human pancreatic islet alpha- and beta-cells will likely lead to the development of therapeutic approaches that will prevent, correct, or at least delay the decline in islet cell function observed in diabetics. In fact, considerable efforts are focused on trying to develop an unlimited source of both insulin and glucagon hormone cells from adult and embryonic stem cells, as a consequence of success in reversing type 1 diabetes by islet transplantation. We believe that long-term success in this endeavor will require a fundamental understanding of the regulatory factors that are required for controlling the specialized genetic programs associated with these cell populations. Our hope is that successful completion of our proposed studies will provide information important for generating acceptable islet-like cells for therapeutic treatment.
The islet cell biology community here is also very interactive and supportive, with twelve groups meeting bi-monthly to discuss their most recent findings. This gives students, post-docs, and faculty a routine opportunity to obtain input from a group of experts.
The Stein program is actively recruiting postdocs with an established background in cell/molecular biology, biochemistry, and/or cell physiology. Notably, several successful trainees have recently left for tenured track Assistant Professorships, including Chad Hunter (UAB, Endocrinology in 2014), Holly Cyphert (Marshall University, Biological Sciences in 2015) & Jason Spaeth (Indiana University – Purdue University Medical Center, Biochemistry in 2018).