Wenbiao Chen, Ph.D.


Faculty Appointments
Professor of Molecular Physiology & Biophysics
Ph.D., Cell and Developmental Biology, Oregon Health & Science University, Portland, OregonM.S., Genetics and Cell Biology, Washington State University, Pullman, WashingtonB.S., Biology, Hunan Normal University, Changsha, China
Office Address
8425A MRB IV
TN 0615
Research Description
Pancreatic alpha and beta cells secrete glucagon and insulin respectively to maintain glucose homeostasis. In conditions that impair the signaling of these hormones, alpha and beta 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 alpha cells and beta 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.
Research Keywords
Genetic basis of susceptibility to type 2 diabetes.
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. Interrupted Glucagon Signaling Reveals Hepatic a Cell Axis and Role for L-Glutamine in a Cell Proliferation. Cell Metab. 2017 Jun 6/6/2017; 25(6): 1362-1373.e5. PMID: 28591638, PII: S1550-4131(17)30300-5, DOI: 10.1016/j.cmet.2017.05.011, ISSN: 1932-7420.

Maddison LA, Chen W. Modeling Pancreatic Endocrine Cell Adaptation and Diabetes in the Zebrafish. Front Endocrinol (Lausanne). 2017; 8: 9. PMID: 28184214, PMCID: PMC5266698, DOI: 10.3389/fendo.2017.00009, ISSN: 1664-2392.

Sasaki T, Lian S, Khan A, Llop JR, Samuelson AV, Chen W, Klionsky DJ, Kishi S. Autolysosome biogenesis and developmental senescence are regulated by both Spns1 and v-ATPase. Autophagy [print-electronic]. 2016 Nov 11/22/2016; 0. PMID: 27875093, DOI: 10.1080/15548627.2016.1256934, ISSN: 1554-8635.

Li M, Zhao L, Page-McCaw PS, Chen W. Zebrafish Genome Engineering Using the CRISPR-Cas9 System. Trends Genet [print-electronic]. 2016 Nov 11/8/2016; PMID: 27836208, PII: S0168-9525(16)30137-8, DOI: 10.1016/j.tig.2016.10.005, ISSN: 0168-9525.

Michel M, Page-McCaw PS, Chen W, Cone RD. Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2016 Mar 3/15/2016; 113(11): 3084-9. PMID: 26903647, PMCID: PMC4801292, PII: 1513212113, DOI: 10.1073/pnas.1513212113, ISSN: 1091-6490.

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. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature [print-electronic]. 2016 Feb 2/4/2016; 530(7588): 57-62. PMID: 26814967, PII: nature16546, DOI: 10.1038/nature16546, ISSN: 1476-4687.

Gong Y, Ma Y, Sinyuk M, Loganathan S, Thompson RC, Sarkaria JN, Chen W, Lathia JD, Mobley BC, Clark SW, Wang J. Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation. Neuro-oncology [print-electronic]. 2016 Jan; 18(1): 48-57. PMID: 26136493, PMCID: PMC4677408, PII: nov096, DOI: 10.1093/neuonc/nov096, ISSN: 1523-5866.

Li M, Page-McCaw P, Chen W. FGF1 Mediates Overnutrition-Induced Compensatory ß-Cell Differentiation. Diabetes [print-electronic]. 2016 Jan; 65(1): 96-109. PMID: 26420862, PII: db15-0085, DOI: 10.2337/db15-0085, ISSN: 1939-327X.

Yin L, Maddison LA, Chen W. Multiplex conditional mutagenesis in zebrafish using the CRISPR/Cas system. Methods Cell Biol [print-electronic]. 2016; 135: 3-17. PMID: 27443918, PII: S0091-679X(16)30052-8, DOI: 10.1016/bs.mcb.2016.04.018, ISSN: 0091-679X.

Li M, Dean ED, Zhao L, Nicholson WE, Powers AC, Chen W. Glucagon receptor inactivation leads to a-cell hyperplasia in zebrafish. J. Endocrinol. 2015 Nov; 227(2): 93-103. PMID: 26446275, PMCID: PMC4598637, PII: 227/2/93, DOI: 10.1530/JOE-15-0284, ISSN: 1479-6805.

Zou P, Wu SY, Koteiche HA, Mishra S, Levic DS, Knapik E, Chen W, Mchaourab HS. A conserved role of aA-crystallin in the development of the zebrafish embryonic lens. Exp. Eye Res [print-electronic]. 2015 Sep; 138: 104-13. PMID: 26149094, PMCID: PMC4638411, PII: S0014-4835(15)00220-1, DOI: 10.1016/j.exer.2015.07.001, ISSN: 1096-0007.

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. High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Genome Res [print-electronic]. 2015 Jul; 25(7): 1030-42. PMID: 26048245, PMCID: PMC4484386, PII: gr.186379.114, DOI: 10.1101/gr.186379.114, ISSN: 1549-5469.

Yin L, Maddison LA, Li M, Kara N, LaFave MC, Varshney GK, Burgess SM, Patton JG, Chen W. Multiplex Conditional Mutagenesis Using Transgenic Expression of Cas9 and sgRNAs. Genetics [print-electronic]. 2015 Jun; 200(2): 431-41. PMID: 25855067, PMCID: PMC4492370, PII: genetics.115.176917, DOI: 10.1534/genetics.115.176917, ISSN: 1943-2631.

Maddison LA, Joest KE, Kammeyer RM, Chen W. Skeletal muscle insulin resistance in zebrafish induces alterations in ß-cell number and glucose tolerance in an age- and diet-dependent manner. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2015 Apr 4/15/2015; 308(8): E662-9. PMID: 25670827, PMCID: PMC4398831, PII: ajpendo.00441.2014, DOI: 10.1152/ajpendo.00441.2014, ISSN: 1522-1555.

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. Circadian modulation of dopamine levels and dopaminergic neuron development contributes to attention deficiency and hyperactive behavior. J. Neurosci. 2015 Feb 2/11/2015; 35(6): 2572-87. PMID: 25673850, PMCID: PMC4323534, PII: 35/6/2572, DOI: 10.1523/JNEUROSCI.2551-14.2015, ISSN: 1529-2401.

Ju B, Chen W, Orr BA, Spitsbergen JM, Jia S, Eden CJ, Henson HE, Taylor MR. Oncogenic KRAS promotes malignant brain tumors in zebrafish. Mol. Cancer. 2015; 14: 18. PMID: 25644510, PMCID: PMC4320811, PII: s12943-015-0288-2, DOI: 10.1186/s12943-015-0288-2, ISSN: 1476-4598.

Yin L, Jao LE, Chen W. Generation of Targeted Mutations in Zebrafish Using the CRISPR/Cas System. Methods Mol. Biol. 2015; 1332: 205-17. PMID: 26285757, DOI: 10.1007/978-1-4939-2917-7_16, ISSN: 1940-6029.

Dirian L, Galant S, Coolen M, Chen W, Bedu S, Houart C, Bally-Cuif L, Foucher I. Spatial regionalization and heterochrony in the formation of adult pallial neural stem cells. Dev. Cell [print-electronic]. 2014 Jul 7/28/2014; 30(2): 123-36. PMID: 25017692, PII: S1534-5807(14)00314-1, DOI: 10.1016/j.devcel.2014.05.012, ISSN: 1878-1551.

Li M, Maddison LA, Page-McCaw P, Chen W. Overnutrition induces ß-cell differentiation through prolonged activation of ß-cells in zebrafish larvae. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2014 Apr 4/1/2014; 306(7): E799-807. PMID: 24473439, PMCID: PMC3962607, PII: ajpendo.00686.2013, DOI: 10.1152/ajpendo.00686.2013, ISSN: 1522-1555.

Maddison LA, Li M, Chen W. Conditional gene-trap mutagenesis in zebrafish. Methods Mol. Biol. 2014; 1101: 393-411. PMID: 24233792, PMCID: PMC4129463, DOI: 10.1007/978-1-62703-721-1_19, ISSN: 1940-6029.

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. Activation of Sonic hedgehog signaling in neural progenitor cells promotes glioma development in the zebrafish optic pathway. Oncogenesis. 2014; 3: e96. PMID: 24686726, PMCID: PMC4038393, PII: oncsis201410, DOI: 10.1038/oncsis.2014.10, ISSN: 2157-9024.

Jao LE, Wente SR, Chen W. Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Aug 8/20/2013; 110(34): 13904-9. PMID: 23918387, PMCID: PMC3752207, PII: 1308335110, DOI: 10.1073/pnas.1308335110, ISSN: 1091-6490.

Li M, Maddison LA, Crees Z, Chen W. Targeted overexpression of CKI-insensitive cyclin-dependent kinase 4 increases functional ß-cell number through enhanced self-replication in zebrafish. Zebrafish [print-electronic]. 2013 Jun; 10(2): 170-6. PMID: 23544990, PMCID: PMC3673610, DOI: 10.1089/zeb.2012.0816, ISSN: 1557-8542.

Maddison LA, Chen W. Nutrient excess stimulates ß-cell neogenesis in zebrafish. Diabetes [print-electronic]. 2012 Oct; 61(10): 2517-24. PMID: 22721970, PMCID: PMC3447891, PII: db11-1841, DOI: 10.2337/db11-1841, ISSN: 1939-327X.

Ni TT, Lu J, Zhu M, Maddison LA, Boyd KL, Huskey L, Ju B, Hesselson D, Zhong TP, Page-McCaw PS, Stainier DY, Chen W. Conditional control of gene function by an invertible gene trap in zebrafish. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2012 Sep 9/18/2012; 109(38): 15389-94. PMID: 22908272, PMCID: PMC3458342, PII: 1206131109, DOI: 10.1073/pnas.1206131109, ISSN: 1091-6490.

Lu J, Maddison LA, Chen W. PhiC31 integrase induces efficient site-specific excision in zebrafish. Transgenic Res [print-electronic]. 2011 Feb; 20(1): 183-9. PMID: 20556509, PMCID: PMC3019273, DOI: 10.1007/s11248-010-9394-5, ISSN: 1573-9368.

Maddison LA, Lu J, Chen W. Generating conditional mutations in zebrafish using gene-trap mutagenesis. Methods Cell Biol. 2011; 104: 1-22. PMID: 21924154, PMCID: PMC3438898, PII: B978-0-12-374814-0.00001-X, DOI: 10.1016/B978-0-12-374814-0.00001-X, ISSN: 0091-679X.

Zhang C, Song Y, Thompson DA, Madonna MA, Millhauser GL, Toro S, Varga Z, Westerfield M, Gamse J, Chen W, Cone RD. Pineal-specific agouti protein regulates teleost background adaptation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Nov 11/23/2010; 107(47): 20164-71. PMID: 20980662, PMCID: PMC2996689, PII: 1014941107, DOI: 10.1073/pnas.1014941107, ISSN: 1091-6490.

Boniface EJ, Lu J, Victoroff T, Zhu M, Chen W. FlEx-based transgenic reporter lines for visualization of Cre and Flp activity in live zebrafish. Genesis. 2009 Jul; 47(7): 484-91. PMID: 19415631, PMCID: PMC3813317, DOI: 10.1002/dvg.20526, ISSN: 1526-968X.

Maddison LA, Lu J, Victoroff T, Scott E, Baier H, Chen W. A gain-of-function screen in zebrafish identifies a guanylate cyclase with a role in neuronal degeneration. Mol. Genet. Genomics [print-electronic]. 2009 May; 281(5): 551-63. PMID: 19221799, PMCID: PMC3814131, DOI: 10.1007/s00438-009-0428-8, ISSN: 1617-4623.

Ju B, Spitsbergen J, Eden CJ, Taylor MR, Chen W. Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish. Mol. Cancer. 2009; 8: 40. PMID: 19555497, PMCID: PMC2711045, PII: 1476-4598-8-40, DOI: 10.1186/1476-4598-8-40, ISSN: 1476-4598.

Jao LE, Maddison L, Chen W, Burgess SM. Using retroviruses as a mutagenesis tool to explore the zebrafish genome. Brief Funct Genomic Proteomic [print-electronic]. 2008 Nov; 7(6): 427-43. PMID: 18977782, PMCID: PMC2722255, PII: eln038, DOI: 10.1093/bfgp/eln038, ISSN: 1477-4062.

Wan L, Almers W, Chen W. Two ribeye genes in teleosts: the role of Ribeye in ribbon formation and bipolar cell development. J. Neurosci. 2005 Jan 1/26/2005; 25(4): 941-9. PMID: 15673675, PII: 25/4/941, DOI: 10.1523/JNEUROSCI.4657-04.2005, ISSN: 1529-2401.

Chen W, Casey Corliss D. Three modules of zebrafish Mind bomb work cooperatively to promote Delta ubiquitination and endocytosis. Dev. Biol. 2004 Mar 3/15/2004; 267(2): 361-73. PMID: 15013799, PII: S001216060300719X, DOI: 10.1016/j.ydbio.2003.11.010, ISSN: 0012-1606.

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. Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Nat. Genet [print-electronic]. 2002 Jun; 31(2): 135-40. PMID: 12006978, PII: ng896, DOI: 10.1038/ng896, ISSN: 1061-4036.

Chen W, Burgess S, Golling G, Amsterdam A, Hopkins N. High-throughput selection of retrovirus producer cell lines leads to markedly improved efficiency of germ line-transmissible insertions in zebra fish. J. Virol. 2002 Mar; 76(5): 2192-8. PMID: 11836396, PMCID: PMC135931, ISSN: 0022-538X.

Burgess S, Reim G, Chen W, Hopkins N, Brand M. 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. Development. 2002 Feb; 129(4): 905-16. PMID: 11861474, ISSN: 0950-1991.

Chen W, Burgess S, Hopkins N. Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Development. 2001 Jun; 128(12): 2385-96. PMID: 11493557, ISSN: 0950-1991.

Amsterdam A, Burgess S, Golling G, Chen W, Sun Z, Townsend K, Farrington S, Haldi M, Hopkins N. A large-scale insertional mutagenesis screen in zebrafish. Genes Dev. 1999 Oct 10/15/1999; 13(20): 2713-24. PMID: 10541557, PMCID: PMC317115, ISSN: 0890-9369.

Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, Cone RD. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell. 1997 Dec 12/12/1997; 91(6): 789-98. PMID: 9413988, PII: S0092-8674(00)80467-5, ISSN: 0092-8674.

Hou X, Li JJ, Chen W, Li SA. Estrogen-induced proto-oncogene and suppressor gene expression in the hamster kidney: significance for estrogen carcinogenesis. Cancer Res. 1996 Jun 6/1/1996; 56(11): 2616-20. PMID: 8653706, ISSN: 0008-5472.

Cone RD, Lu D, Koppula S, Vage DI, Klungland H, Boston B, Chen W, Orth DN, Pouton C, Kesterson RA. The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Prog. Horm. Res. 1996; 51: 287-317; discussion 318. PMID: 8701084, ISSN: 0079-9963.

Chen W, Shields TS, Stork PJ, Cone RD. A colorimetric assay for measuring activation of Gs- and Gq-coupled signaling pathways. Anal. Biochem. 1995 Apr 4/10/1995; 226(2): 349-54. PMID: 7793637, PII: S0003269785712353, ISSN: 0003-2697.