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. RIPK3-mediated inflammation is a conserved β cell response to ER stress. Yang B, Maddison LA, Zaborska KE, Dai C, Yin L, Tang Z, Zang L, Jacobson DA, Powers AC, Chen W (2020) Sci Adv 6(51)
    › Primary publication · 33355143 (PubMed)
  2. Taste buds are not derived from neural crest in mouse, chicken, and zebrafish. Yu W, Wang Z, Marshall B, Yoshida Y, Patel R, Cui X, Ball R, Yin L, Kawabata F, Tabata S, Chen W, Kelsh RN, Lauderdale JD, Liu HX (2021) Dev Biol : 76-88
    › Primary publication · 33326797 (PubMed) · PMC7855483 (PubMed Central)
  3. Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species. Alexander MR, Schoeder CT, Brown JA, Smart CD, Moth C, Wikswo JP, Capra JA, Meiler J, Chen W, Madhur MS (2020) FASEB J 34(12): 15946-15960
    › Primary publication · 33015868 (PubMed) · PMC7675292 (PubMed Central)
  4. In vivo generation and regeneration of β cells in zebrafish. Yang B, Covington BA, Chen W (2020) Cell Regen 9(1): 9
    › Primary publication · 32613468 (PubMed) · PMC7329966 (PubMed Central)
  5. Systematic genome editing of the genes spanning an entire chromosome by CRISPR/Cas9 in a vertebrate-zebrafish (Danio rerio). Gong Y, Yang B, Chen W (2020) Sci China Life Sci 63(7): 1096-1097
    › Primary publication · 32140907 (PubMed) · PMC8608268 (PubMed Central)
  6. Global Transcriptomic Analysis of Zebrafish Glucagon Receptor Mutant Reveals Its Regulated Metabolic Network. Kang Q, Hu M, Jia J, Bai X, Liu C, Wu Z, Chen W, Li M (2020) Int J Mol Sci 21(3)
    › Primary publication · 31979106 (PubMed) · PMC7037442 (PubMed Central)
  7. Therapeutic Silencing of Centromere Protein X Ameliorates Hyperglycemia in Zebrafish and Mouse Models of Type 2 Diabetes Mellitus. Zang L, Shimada Y, Nakayama H, Chen W, Okamoto A, Koide H, Oku N, Dewa T, Shiota M, Nishimura N (2019) Front Genet : 693
    › Primary publication · 31417608 (PubMed) · PMC6681619 (PubMed Central)
  8. Zebrafish as a Model for Obesity and Diabetes. Zang L, Maddison LA, Chen W (2018) Front Cell Dev Biol : 91
    › Primary publication · 30177968 (PubMed) · PMC6110173 (PubMed Central)
  9. Interrupted Glucagon Signaling Reveals Hepatic α Cell Axis and Role for L-Glutamine in α Cell Proliferation. Dean ED, Li M, Prasad N, Wisniewski SN, Von Deylen A, Spaeth J, Maddison L, Botros A, Sedgeman LR, Bozadjieva N, Ilkayeva O, Coldren A, Poffenberger G, Shostak A, Semich MC, Aamodt KI, Phillips N, Yan H, Bernal-Mizrachi E, Corbin JD, Vickers KC, Levy SE, Dai C, Newgard C, Gu W, Stein R, Chen W, Powers AC (2017) Cell Metab 25(6): 1362-1373.e5
    › Primary publication · 28591638 (PubMed) · PMC5572896 (PubMed Central)
  10. Modeling Pancreatic Endocrine Cell Adaptation and Diabetes in the Zebrafish. Maddison LA, Chen W (2017) Front Endocrinol (Lausanne) : 9
    › Primary publication · 28184214 (PubMed) · PMC5266698 (PubMed Central)
  11. Autolysosome biogenesis and developmental senescence are regulated by both Spns1 and v-ATPase. Sasaki T, Lian S, Khan A, Llop JR, Samuelson AV, Chen W, Klionsky DJ, Kishi S (2017) Autophagy 13(2): 386-403
    › Primary publication · 27875093 (PubMed) · PMC5324850 (PubMed Central)
  12. Zebrafish Genome Engineering Using the CRISPR-Cas9 System. Li M, Zhao L, Page-McCaw PS, Chen W (2016) Trends Genet 32(12): 815-827
    › Primary publication · 27836208 (PubMed) · PMC5127170 (PubMed Central)
  13. Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish. Michel M, Page-McCaw PS, Chen W, Cone RD (2016) Proc Natl Acad Sci U S A 113(11): 3084-9
    › Primary publication · 26903647 (PubMed) · PMC4801292 (PubMed Central)
  14. 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)
  15. 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)
  16. 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)
  17. 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)
  18. 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)
  19. 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)
  20. 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)
  21. 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)
  22. 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)
  23. 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)
  24. 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)
  25. 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)
  26. 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)
  27. 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)
  28. 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)
  29. 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)
  30. 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)
  31. 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)
  32. 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)
  33. 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)
  34. 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)
  35. 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)
  36. 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)
  37. 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)
  38. 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)
  39. 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)
  40. Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Golling G, Amsterdam A, Sun Z, Antonelli M, Maldonado E, Chen W, Burgess S, Haldi M, Artzt K, Farrington S, Lin SY, Nissen RM, Hopkins N (2002) Nat Genet 31(2): 135-40
    › Primary publication · 12006978 (PubMed)
  41. The zebrafish spiel-ohne-grenzen (spg) gene encodes the POU domain protein Pou2 related to mammalian Oct4 and is essential for formation of the midbrain and hindbrain, and for pre-gastrula morphogenesis. Burgess S, Reim G, Chen W, Hopkins N, Brand M (2002) Development 129(4): 905-16
    › Primary publication · 11861474 (PubMed)
  42. High-throughput selection of retrovirus producer cell lines leads to markedly improved efficiency of germ line-transmissible insertions in zebra fish. Chen W, Burgess S, Golling G, Amsterdam A, Hopkins N (2002) J Virol 76(5): 2192-8
    › Primary publication · 11836396 (PubMed) · PMC135931 (PubMed Central)
  43. Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Chen W, Burgess S, Hopkins N (2001) Development 128(12): 2385-96
    › Primary publication · 11493557 (PubMed)
  44. A large-scale insertional mutagenesis screen in zebrafish. Amsterdam A, Burgess S, Golling G, Chen W, Sun Z, Townsend K, Farrington S, Haldi M, Hopkins N (1999) Genes Dev 13(20): 2713-24
    › Primary publication · 10541557 (PubMed) · PMC317115 (PubMed Central)
  45. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, Cone RD (1997) Cell 91(6): 789-98
    › Primary publication · 9413988 (PubMed)
  46. The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Cone RD, Lu D, Koppula S, Vage DI, Klungland H, Boston B, Chen W, Orth DN, Pouton C, Kesterson RA (1996) Recent Prog Horm Res : 287-317; discussion 318
    › Primary publication · 8701084 (PubMed)
  47. A colorimetric assay for measuring activation of Gs- and Gq-coupled signaling pathways. Chen W, Shields TS, Stork PJ, Cone RD (1995) Anal Biochem 226(2): 349-54
    › Primary publication · 7793637 (PubMed)