The Gu laboratory studies the developmental biology of the pancreas in both mouse and chicken models. The vertebrate pancreas has two functions: providing digestive enzymes for food digestion and endocrine hormones for regulating energy metabolism.  The exocrine pancreas, comprised of acinar and pancreatic duct cells perform the former function.  The endocrine islets of Langerhans secrete hormones into the blood stream for the latter.  Four major islet cell types reside in the islets.  They are alpha, beta, delta, and PP cells that secrete glucagon, insulin, somatostatin, and pancreatic polypeptide, respectively.  Dysfunction of endocrine islets, especially the insulin secreting beta cells, results in diabetes. Our goals are to unravel the molecular and cellular mechanisms regulating pancreatic development and endocrine islet cell function, and translate these basic understandings to therapeutic strategies for diabetes.


Our current studies centered on the factor/pathways that regulate the differentiation of pancreatic progenitors to beta cells, beta cell maturation/insulin secretion, and beta cell functional maintenance.


1)    Allocation of pancreatic progenitors to pancreatic beta cells.  All pancreatic cells derive from a common set of endodermal pancreatic progenitors in later gestation.  We ask why a specific portion of these progenitors becomes beta cells.  By designing innovative tool and utilizing elegant genetic studies, we explore how cell-cell communications via membrane proteins restrict the activation of a proendocrine gene, Neurogenin 3, in a specific number of cells to activate their endocrine program.  We then determine the combination of transcription factors  and mechanisms that specify particular progenitors to beta cell fate. 

2)    Controlling beta cell maturation and insulin secretion. When beta cells were first made, i.e. when insulin vesicles are first achieved in cells, they do not secrete insulin when stimulated with nutrients.  These immature cells have to re-organize their molecular machinery to make cells glucose responsive.  By examining the gene expression pattern and correlate them with insulin secretion, we have revealed several genetic networks, including the factors that regulate neural transmission, that accompany beta cell maturation.  We are testing whether manipulating these pathways expedite beta cell maturation by facilitating insulin secretion. Furthermore, we also collaborate with colleagues to examine whether the cytoskeletal networks in beta cells paly any roles in insulin secretion regulation.

3)    Beta cell mass maintenance.  In postnatal life, beta cells proliferate to compensate for bodily growth and beta cell death, so that a specific beta cell mass is maintained in each individual. By examining beta cell division and mass, we have found that there is an inverse relationship between beta cell proliferation and the insulin secretion capability of beta cells.  We are currently pursuing a hypothesis that an autocrine mechanism is utilized to ensure that each individual to produce a sufficient amount of insulin secreting ability (i.e. a combination of beta cell mass and secreting efficiency). We also investigate the mechanisms underlying beta cell survival.  We have revealed a Myt1 transcription factor-organized pathway that maintains beta cell survival during insulin secretion.  We envision that this mechanism is highly relevant to the development of Type II diabetes in human subjects, which is postulated to be a matter of beta cell death induced by over insulin secretion.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Microtubules Negatively Regulate Insulin Secretion in Pancreatic β Cells. Zhu X, Hu R, Brissova M, Stein RW, Powers AC, Gu G, Kaverina I (2015) Dev Cell 34(6): 656-68
    › Primary publication · 26418295 (PubMed) · PMC4594944 (PubMed Central)
  2. Effects of Sevoflurane on Young Male Adult C57BL/6 Mice Spatial Cognition. Liu J, Zhang X, Zhang W, Gu G, Wang P (2015) PLoS One 10(8): e0134217
    › Primary publication · 26285216 (PubMed) · PMC4540577 (PubMed Central)
  3. Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers. Chera S, Baronnier D, Ghila L, Cigliola V, Jensen JN, Gu G, Furuyama K, Thorel F, Gribble FM, Reimann F, Herrera PL (2014) Nature 514(7523): 503-7
    › Primary publication · 25141178 (PubMed) · PMC4209186 (PubMed Central)
  4. Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Yanger K, Knigin D, Zong Y, Maggs L, Gu G, Akiyama H, Pikarsky E, Stanger BZ (2014) Cell Stem Cell 15(3): 340-349
    › Primary publication · 25130492 (PubMed) · PMC4505916 (PubMed Central)
  5. Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells. Sancho R, Gruber R, Gu G, Behrens A (2014) Cell Stem Cell 15(2): 139-53
    › Primary publication · 25105579 (PubMed) · PMC4136739 (PubMed Central)
  6. Generation of a tenascin-C-CreER2 knockin mouse line for conditional DNA recombination in renal medullary interstitial cells. He W, Xie Q, Wang Y, Chen J, Zhao M, Davis LS, Breyer MD, Gu G, Hao CM (2013) PLoS One 8(11): e79839
    › Primary publication · 24244568 (PubMed) · PMC3823583 (PubMed Central)
  7. Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice. Baeyens L, Lemper M, Leuckx G, De Groef S, Bonfanti P, Stangé G, Shemer R, Nord C, Scheel DW, Pan FC, Ahlgren U, Gu G, Stoffers DA, Dor Y, Ferrer J, Gradwohl G, Wright CV, Van de Casteele M, German MS, Bouwens L, Heimberg H (2014) Nat Biotechnol 32(1): 76-83
    › Primary publication · 24240391 (PubMed) · PMC4096987 (PubMed Central)
  8. Reconstituting pancreas development from purified progenitor cells reveals genes essential for islet differentiation. Sugiyama T, Benitez CM, Ghodasara A, Liu L, McLean GW, Lee J, Blauwkamp TA, Nusse R, Wright CV, Gu G, Kim SK (2013) Proc Natl Acad Sci U S A 110(31): 12691-6
    › Primary publication · 23852729 (PubMed) · PMC3732989 (PubMed Central)
  9. Non-parallel recombination limits Cre-LoxP-based reporters as precise indicators of conditional genetic manipulation. Liu J, Willet SG, Bankaitis ED, Xu Y, Wright CV, Gu G (2013) Genesis 51(6): 436-42
    › Primary publication · 23441020 (PubMed) · PMC3696028 (PubMed Central)
  10. Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas. Wang S, Yan J, Anderson DA, Xu Y, Kanal MC, Cao Z, Wright CV, Gu G (2010) Dev Biol 339(1): 26-37
    › Primary publication · 20025861 (PubMed) · PMC2824035 (PubMed Central)
  11. Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function. Wang S, Jensen JN, Seymour PA, Hsu W, Dor Y, Sander M, Magnuson MA, Serup P, Gu G (2009) Proc Natl Acad Sci U S A 106(24): 9715-20
    › Primary publication · 19487660 (PubMed) · PMC2701002 (PubMed Central)
  12. A CK19(CreERT) knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs. Means AL, Xu Y, Zhao A, Ray KC, Gu G (2008) Genesis 46(6): 318-23
    › Primary publication · 18543299 (PubMed) · PMC3735352 (PubMed Central)
  13. MafA is a dedicated activator of the insulin gene in vivo. Artner I, Hang Y, Guo M, Gu G, Stein R (2008) J Endocrinol 198(2): 271-9
    › Primary publication · 18515495 (PubMed) · PMC3787904 (PubMed Central)
  14. Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. Wang S, Hecksher-Sorensen J, Xu Y, Zhao A, Dor Y, Rosenberg L, Serup P, Gu G (2008) Dev Biol 317(2): 531-40
    › Primary publication · 18394599 (PubMed) · PMC2423199 (PubMed Central)
  15. Evidence for an inhibition of thyroid hormone effects during chronic treatment with amiodarone. Beck-Peccoz P, Volpi A, Maggioni AP, Cattaneo MG, Piscitelli G, Giani P, Landolina M, Tognoni G, Faglia G (1986) Horm Metab Res 18(6): 411-4
    › Primary publication · 3732989 (PubMed)