Pancreatic a and b cells secrete glucagon and insulin respectively to maintain glucose homeostasis. In conditions that impair the signaling of these hormones, a and b cells compensate by increasing their number and augmenting their secretion. Defects in the compensatory responses lead to defects in glucose homeostasis. The molecular mechanisms underlying the compensatory responses remain incompletely understood. The Chen laboratory found that compensatory responses of pancreatic a cells and b cells is conserved in zebrafish, a vertebrate model amenable for live imaging as well as large-scale genetic and chemical screens. We combine genetic, pharmacological, and imaging techniques to identify genes essential for the compensatory responses and to define their roles in diabetes.


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

Featured publications are shown below:

  1. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Lin CY, Erkek S, Tong Y, Yin L, Federation AJ, Zapatka M, Haldipur P, Kawauchi D, Risch T, Warnatz HJ, Worst BC, Ju B, Orr BA, Zeid R, Polaski DR, Segura-Wang M, Waszak SM, Jones DT, Kool M, Hovestadt V, Buchhalter I, Sieber L, Johann P, Chavez L, Gröschel S, Ryzhova M, Korshunov A, Chen W, Chizhikov VV, Millen KJ, Amstislavskiy V, Lehrach H, Yaspo ML, Eils R, Lichter P, Korbel JO, Pfister SM, Bradner JE, Northcott PA (2016) Nature 530(7588): 57-62
    › Primary publication · 26814967 (PubMed) · PMC5168934 (PubMed Central)
  2. Glucagon receptor inactivation leads to α-cell hyperplasia in zebrafish. Li M, Dean ED, Zhao L, Nicholson WE, Powers AC, Chen W (2015) J Endocrinol 227(2): 93-103
    › Primary publication · 26446275 (PubMed) · PMC4598637 (PubMed Central)
  3. FGF1 Mediates Overnutrition-Induced Compensatory β-Cell Differentiation. Li M, Page-McCaw P, Chen W (2016) Diabetes 65(1): 96-109
    › Primary publication · 26420862 (PubMed) · PMC4686947 (PubMed Central)
  4. Generation of Targeted Mutations in Zebrafish Using the CRISPR/Cas System. Yin L, Jao LE, Chen W (2015) Methods Mol Biol : 205-17
    › Primary publication · 26285757 (PubMed)
  5. A conserved role of αA-crystallin in the development of the zebrafish embryonic lens. Zou P, Wu SY, Koteiche HA, Mishra S, Levic DS, Knapik E, Chen W, Mchaourab HS (2015) Exp Eye Res : 104-13
    › Primary publication · 26149094 (PubMed) · PMC4638411 (PubMed Central)
  6. Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation. Gong Y, Ma Y, Sinyuk M, Loganathan S, Thompson RC, Sarkaria JN, Chen W, Lathia JD, Mobley BC, Clark SW, Wang J (2016) Neuro Oncol 18(1): 48-57
    › Primary publication · 26136493 (PubMed) · PMC4677408 (PubMed Central)
  7. High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Varshney GK, Pei W, LaFave MC, Idol J, Xu L, Gallardo V, Carrington B, Bishop K, Jones M, Li M, Harper U, Huang SC, Prakash A, Chen W, Sood R, Ledin J, Burgess SM (2015) Genome Res 25(7): 1030-42
    › Primary publication · 26048245 (PubMed) · PMC4484386 (PubMed Central)
  8. Multiplex Conditional Mutagenesis Using Transgenic Expression of Cas9 and sgRNAs. Yin L, Maddison LA, Li M, Kara N, LaFave MC, Varshney GK, Burgess SM, Patton JG, Chen W (2015) Genetics 200(2): 431-41
    › Primary publication · 25855067 (PubMed) · PMC4492370 (PubMed Central)
  9. Circadian modulation of dopamine levels and dopaminergic neuron development contributes to attention deficiency and hyperactive behavior. Huang J, Zhong Z, Wang M, Chen X, Tan Y, Zhang S, He W, He X, Huang G, Lu H, Wu P, Che Y, Yan YL, Postlethwait JH, Chen W, Wang H (2015) J Neurosci 35(6): 2572-87
    › Primary publication · 25673850 (PubMed) · PMC4323534 (PubMed Central)
  10. Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner. Maddison LA, Joest KE, Kammeyer RM, Chen W (2015) Am J Physiol Endocrinol Metab 308(8): E662-9
    › Primary publication · 25670827 (PubMed) · PMC4398831 (PubMed Central)
  11. Oncogenic KRAS promotes malignant brain tumors in zebrafish. Ju B, Chen W, Orr BA, Spitsbergen JM, Jia S, Eden CJ, Henson HE, Taylor MR (2015) Mol Cancer : 18
    › Primary publication · 25644510 (PubMed) · PMC4320811 (PubMed Central)
  12. Spatial regionalization and heterochrony in the formation of adult pallial neural stem cells. Dirian L, Galant S, Coolen M, Chen W, Bedu S, Houart C, Bally-Cuif L, Foucher I (2014) Dev Cell 30(2): 123-36
    › Primary publication · 25017692 (PubMed)
  13. Activation of Sonic hedgehog signaling in neural progenitor cells promotes glioma development in the zebrafish optic pathway. Ju B, Chen W, Spitsbergen JM, Lu J, Vogel P, Peters JL, Wang YD, Orr BA, Wu J, Henson HE, Jia S, Parupalli C, Taylor MR (2014) Oncogenesis : e96
    › Primary publication · 24686726 (PubMed) · PMC4038393 (PubMed Central)
  14. Overnutrition induces β-cell differentiation through prolonged activation of β-cells in zebrafish larvae. Li M, Maddison LA, Page-McCaw P, Chen W (2014) Am J Physiol Endocrinol Metab 306(7): E799-807
    › Primary publication · 24473439 (PubMed) · PMC3962607 (PubMed Central)
  15. Conditional gene-trap mutagenesis in zebrafish. Maddison LA, Li M, Chen W (2014) Methods Mol Biol : 393-411
    › Primary publication · 24233792 (PubMed) · PMC4129463 (PubMed Central)
  16. Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Jao LE, Wente SR, Chen W (2013) Proc Natl Acad Sci U S A 110(34): 13904-9
    › Primary publication · 23918387 (PubMed) · PMC3752207 (PubMed Central)
  17. Targeted overexpression of CKI-insensitive cyclin-dependent kinase 4 increases functional β-cell number through enhanced self-replication in zebrafish. Li M, Maddison LA, Crees Z, Chen W (2013) Zebrafish 10(2): 170-6
    › Primary publication · 23544990 (PubMed) · PMC3673610 (PubMed Central)
  18. Generating conditional mutations in zebrafish using gene-trap mutagenesis. Maddison LA, Lu J, Chen W (2011) Methods Cell Biol : 1-22
    › Primary publication · 21924154 (PubMed) · PMC3438898 (PubMed Central)
  19. Pineal-specific agouti protein regulates teleost background adaptation. Zhang C, Song Y, Thompson DA, Madonna MA, Millhauser GL, Toro S, Varga Z, Westerfield M, Gamse J, Chen W, Cone RD (2010) Proc Natl Acad Sci U S A 107(47): 20164-71
    › Primary publication · 20980662 (PubMed) · PMC2996689 (PubMed Central)
  20. PhiC31 integrase induces efficient site-specific excision in zebrafish. Lu J, Maddison LA, Chen W (2011) Transgenic Res 20(1): 183-9
    › Primary publication · 20556509 (PubMed) · PMC3019273 (PubMed Central)
  21. Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish. Ju B, Spitsbergen J, Eden CJ, Taylor MR, Chen W (2009) Mol Cancer : 40
    › Primary publication · 19555497 (PubMed) · PMC2711045 (PubMed Central)
  22. FlEx-based transgenic reporter lines for visualization of Cre and Flp activity in live zebrafish. Boniface EJ, Lu J, Victoroff T, Zhu M, Chen W (2009) Genesis 47(7): 484-91
    › Primary publication · 19415631 (PubMed) · PMC3813317 (PubMed Central)
  23. A gain-of-function screen in zebrafish identifies a guanylate cyclase with a role in neuronal degeneration. Maddison LA, Lu J, Victoroff T, Scott E, Baier H, Chen W (2009) Mol Genet Genomics 281(5): 551-63
    › Primary publication · 19221799 (PubMed) · PMC3814131 (PubMed Central)
  24. Using retroviruses as a mutagenesis tool to explore the zebrafish genome. Jao LE, Maddison L, Chen W, Burgess SM (2008) Brief Funct Genomic Proteomic 7(6): 427-43
    › Primary publication · 18977782 (PubMed) · PMC2722255 (PubMed Central)
  25. Two ribeye genes in teleosts: the role of Ribeye in ribbon formation and bipolar cell development. Wan L, Almers W, Chen W (2005) J Neurosci 25(4): 941-9
    › Primary publication · 15673675 (PubMed) · PMC6725632 (PubMed Central)
  26. Three modules of zebrafish Mind bomb work cooperatively to promote Delta ubiquitination and endocytosis. Chen W, Casey Corliss D (2004) Dev Biol 267(2): 361-73
    › Primary publication · 15013799 (PubMed)