Assistant Professor
Phone: 615-936-3634My lab investigates the developmental biology of pancreas. The vertebrate pancreas includes two glands that perform separate functions. Exocrine acini and pancreatic ducts form the exocrine pancreas that secretes enzymes for food digestion. Four major types of endocirne cells comprise the endocrine islets of Langerhans. These islet cells secrete peptide hormones into the blood stream to regulate lipid and glucose metabolism. Illnesses associated with endocrine pancreas malfunction include diabetes mellitus and pancreatic cancer. Diabetes inflicts more than 17 million people in the United States alone, and the prognosis of pancreatic cancer is dismal.
In order to understand the mechanism of diabetes development and to design cures for this debilitating disease, we set to investigate the normal differentiation procedure of the endocrine islets. Our effort includes first to identify the stem/progenitor cells that specifically give rise to islet cells and then identify the genes that are specifically expressed and are functionally required within these endocrine precursors. The identification of the pancreatic cell lineages (i.e., to look for the progenitor cells for each type of mature pancreatic tissues) is made possible by a temporally controlled Cre-ER-LoxP system that marks and follows cell fate in vivo.
Through cell marking, sorting, and high-density cDNA microarrays, we have identified a number of genes that are specifically expressed in endocrine progenitors. We plan to investigate the function of each candidate gene by generating transgenic chick embryos, transgenic mice, or knockout mice. Utilizing this system, I am specifically interested in studying the functions of transcription factors and notch signaling modifiers for endocrine cells differentiation. Our preliminary data indicated that transcription factor Myt1 and the fringe molecules (the notch modifiers) are sufficient to initiate endocrine differentiation in the endodermal epithelium. We are currently generating knockout mice to verify their function during normal endocrine islet development.
| PubMedID | Citation |
|---|---|
| 19487660 | Wang S, Jensen JN, Seymour PA, Hsu W, Dor Y, Sander M, Magnuson MA, Serup P, Gu G. Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function. (2009) Proc Natl Acad Sci U S A 106: 9715-20 |
| 18543299 | Means AL, Xu Y, Zhao A, Ray KC, Gu G. A CK19(CreERT) knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs. () Genesis 46: 318-23 |
| 18515495 | Artner I, Hang Y, Guo M, Gu G, Stein R. MafA is a dedicated activator of the insulin gene in vivo. (2008) J Endocrinol 198: 271-9 |
| 18394599 | Wang S, Hecksher-Sorensen J, Xu Y, Zhao A, Dor Y, Rosenberg L, Serup P, Gu G. Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. (2008) Dev Biol 317: 531-40 |
| 17510410 | Gu G, Yuan J, Wills M, Kasper S. Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. () Cancer Res 67: 4807-15 |
You can also view publications listed at PubMed.