ZFIN ID: ZDB-LAB-070402-1
Zhaoxia Sun lab
PI/Director: Sun, Zhaoxia
Contact Person: Sun, Zhaoxia
Email: zhaoxia.sun@yale.edu
URL: http://info.med.yale.edu/genetics/fac/ZhaoxiaSun.php
Address: Department of Genetics Yale University School of Medicine P.O. Box 208005 333 Cedar ST., NSB-393 New Haven, CT 06520-8005
Country: United States
Phone: 203-785-3589
Fax: 203-785-7227
Line Designation: ya

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My lab uses zebrafish, a vertebrate system amenable to both genetic and embryonic analyses, to study kidney development and diseases. Currently, we are focusing on polycystic kidney disease (PKD). Understanding PKD is of profound medical importance. Striking one in 1000 live births, autosomal dominant form of PKD (ADPKD) is among the most common monogenetic disorders in humans. PKD1 and PKD2, two genes cloned for ADPKD, encode two membrane proteins polycystin-1 (Pc1) and polycystin-2 (Pc2). Pc1 is a large novel protein, while Pc2 belongs to the TRP channel superfamily, members of which frequently function as mechano-sensory channels. How the functions of Pc1 and Pc2 are regulated, their downstream signaling events, as well as the molecular pathogenesis of PKD remains to be elucidated. In a large-scale insertional mutagenesis screen in zebrafish, I identified 12 genes that can cause kidney cyst when mutated. Two of the genes, vHNF1 and PKD2, are known human PKD genes, indicating that zebrafish cystic kidney mutants are highly relevant to human PKD. Interestingly, three of the mutated genes encode components of IFT (intraflagellar transport) particles, which are required for the formation and maintenance of flagellum and cilium. We are now using this group of cystic kidney mutants as entry points to address multiple questions. First, how is the cilium built during development? Second, how is signal sensed by cilia? Third, how does signal from cilia eventually regulate tube size? Our goal is to tease out the signaling network coupling ciliary signal to size control mechanisms of the renal tube.

DiBella, Linda Post-Doc Kishimoto, Norihito Post-Doc Lee, Sunjin Post-Doc
Duldulao, Neil Graduate Student Park, Alice Graduate Student Dillon, Nicole Research Staff

Li, Y., Xu, W., Jerman, S., Sun, Z. (2019) In vivo analysis of renal epithelial cells in zebrafish. Methods in cell biology. 154:163-181
Merrick, D., Mistry, K., Wu, J., Gresko, N., Baggs, J.E., Hogenesch, J.B., Sun, Z., Caplan, M.J. (2018) Polycystin-1 regulates bone development through an interaction with the transcriptional co-activator taz. Human molecular genetics. 28(1):16-30
Li, Y., Zhao, L., Yuan, S., Zhang, J., Sun, Z. (2017) Axonemal dynein assembly requires the R2TP complex component Pontin. Development (Cambridge, England). 144(24):4684-4693
Jerman, S., Sun, Z. (2017) Using Zebrafish to Study Kidney Development and Disease. Current topics in developmental biology. 124:41-79
Li, Y., Tian, X., Ma, M., Jerman, S., Kong, S., Somlo, S., Sun, Z. (2016) Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts. Journal of the American Society of Nephrology : JASN. 27(12):3628-3638
Soens, Z.T., Li, Y., Zhao, L., Eblimit, A., Dharmat, R., Li, Y., Chen, Y., Naqeeb, M., Fajardo, N., Lopez, I., Sun, Z., Koenekoop, R.K., Chen, R. (2016) Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. Genetics in medicine : official journal of the American College of Medical Genetics. 18(10):1044-51
Kallakuri, S., Yu, J.A., Li, J., Li, Y., Weinstein, B.M., Nicoli, S., Sun, Z. (2015) Endothelial Cilia Are Essential for Developmental Vascular Integrity in Zebrafish. Journal of the American Society of Nephrology : JASN. 26(4):864-75
Yuan, S., Zhao, L., Brueckner, M., Sun, Z. (2015) Intraciliary Calcium Oscillations Initiate Vertebrate Left-Right Asymmetry. Current biology : CB. 25(5):556-67
Aldahmesh, M.A., Li, Y., Alhashem, A., Anazi, S., Alkuraya, H., Hashem, M., Awaji, A.A., Sogaty, S., Alkharashi, A., Alzahrani, S., Al Hazzaa, S.A., Xiong, Y., Kong, S., Sun, Z., and Alkuraya, F.S. (2014) IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome. Human molecular genetics. 23(12):3307-15
Zariwala, M.A., Gee, H.Y., Kurkowiak, M., Al-Mutairi, D.A., Leigh, M.W., Hurd, T.W., Hjeij, R., Dell, S.D., Chaki, M., Dougherty, G.W., Adan, M., Spear, P.C., Esteve-Rudd, J., Loges, N.T., Rosenfeld, M., Diaz, K.A., Olbrich, H., Wolf, W.E., Sheridan, E., Batten, T.F., Halbritter, J., Porath, J.D., Kohl, S., Lovric, S., Hwang, D.Y., Pittman, J.E., Burns, K.A., Ferkol, T.W., Sagel, S.D., Olivier, K.N., Morgan, L.C., Werner, C., Raidt, J., Pennekamp, P., Sun, Z., Zhou, W., Airik, R., Natarajan, S., Allen, S.J., Amirav, I., Wieczorek, D., Landwehr, K., Nielsen, K., Schwerk, N., Sertic, J., Köhler, G., Washburn, J., Levy, S., Fan, S., Koerner-Rettberg, C., Amselem, S., Williams, D.S., Mitchell, B.J., Drummond, I.A., Otto, E.A., Omran, H., Knowles, M.R., and Hildebrandt, F. (2013) ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6. American journal of human genetics. 93(2):336-345
Zhao, L., Yuan, S., Cao, Y., Kallakuri, S., Li, Y., Kishimoto, N., Dibella, L., and Sun, Z. (2013) Reptin/Ruvbl2 is a Lrrc6/Seahorse interactor essential for cilia motility. Proceedings of the National Academy of Sciences of the United States of America. 110(31):12697-702
Kishimoto, N., Asakawa, K., Madelaine, R., Blader, P., Kawakami, K., and Sawamoto, K. (2013) Interhemispheric asymmetry of olfactory input-dependent neuronal specification in the adult brain. Nature Neuroscience. 16(7):884-8
Paavola, J., Schliffke, S., Rossetti, S., Kuo, I.Y., Yuan, S., Sun, Z., Harris, P.C., Torres, V.E., and Ehrlich, B.E. (2013) Polycystin-2 mutations lead to impaired calcium cycling in the heart and predispose to dilated cardiomyopathy. Journal of Molecular and Cellular Cardiology. 58:199-208
Yuan, S., Zhao, L., and Sun, Z. (2013) Dissecting the Functional Interplay Between the TOR Pathway and the Cilium in Zebrafish. Methods in enzymology. 525:159-189
Kishimoto, N., Shimizu, K., and Sawamoto, K. (2012) Neuronal regeneration in a zebrafish model of adult brain injury. Disease models & mechanisms. 5(2):200-209
Yuan, S., Li, J., Diener, D.R., Choma, M.A., Rosenbaum, J.L., and Sun, Z. (2012) Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation. Proceedings of the National Academy of Sciences of the United States of America. 109(6):2021-2026
Merrick, D., Chapin, H., Baggs, J.E., Yu, Z., Somlo, S., Sun, Z., Hogenesch, J.B., and Caplan, M.J. (2012) The γ-Secretase Cleavage Product of Polycystin-1 Regulates TCF and CHOP-Mediated Transcriptional Activation through a p300-Dependent Mechanism. Developmental Cell. 22(1):197-210
Kishimoto, N., Alfaro-Cervello, C., Shimizu, K., Asakawa, K., Urasaki, A., Nonaka, S., Kawakami, K., Garcia-Verdugo, J.M., and Sawamoto, K. (2011) Migration of neuronal precursors from the telencephalic ventricular zone into the olfactory bulb in adult zebrafish. The Journal of comparative neurology. 519(17):3549-65
Li, J., and Sun, Z. (2011) Qilin is essential for cilia assembly and normal kidney development in zebrafish. PLoS One. 6(11):e27365
Malicki, J., Avanesov, A., Li, J., Yuan, S., and Sun, Z. (2011) Analysis of cilia structure and function in zebrafish. Methods (San Diego, Calif.). 101:39-74
Hellman, N.E., Liu, Y., Merkel, E., Austin, C., Le Corre, S., Beier, D.R., Sun, Z., Sharma, N., Yoder, B.K., and Drummond, I.A. (2010) The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch. Proceedings of the National Academy of Sciences of the United States of America. 107(43):18499-18504
Cao, Y., Park, A., and Sun, Z. (2010) Intraflagellar Transport Proteins Are Essential for Cilia Formation and for Planar Cell Polarity. Journal of the American Society of Nephrology : JASN. 21(8):1326-1333
Cao, Y., Semanchik, N., Lee, S.H., Somlo, S., Barbano, P.E., Coifman, R., and Sun, Z. (2009) Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models. Proceedings of the National Academy of Sciences of the United States of America. 106(51):21819-21824
Duldulao, N.A., Lee, S., and Sun, Z. (2009) Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion. Development (Cambridge, England). 136(23):4033-4042
Yuan, S., and Sun, Z. (2009) Microinjection of mRNA and morpholino antisense oligonucleotides in zebrafish embryos. Journal of visualized experiments : JoVE. (27)
Dibella, L.M., Park, A., and Sun, Z. (2009) Zebrafish Tsc1 Reveals Functional Interactions Between the Cilium and the TOR Pathway. Human molecular genetics. 18(4):595-606
Kishimoto, N., Cao, Y., Park, A., and Sun, Z. (2008) Cystic kidney gene seahorse regulates cilia-mediated processes and Wnt pathways. Developmental Cell. 14(6):954-961
Amsterdam, A., Nissen, R.M., Sun, Z., Swindell, E., Farrington, S., and Hopkins, N. (2005) Submission and curation of data from an insertional mutagenesis screen. ZFIN Direct Data Submission.
Amsterdam, A., Nissen, R.M., Sun, Z., Swindell, E., Farrington, S., and Hopkins, N. (2004) Identification of 315 genes essential for early zebrafish development. Proceedings of the National Academy of Sciences of the United States of America. 101(35):12792-12797
Sun, Z., Amsterdam, A., Pazour, G.J., Cole, D.G., Miller, M.S. and Hopkins, N. (2004) A Genetic Screen in Zebrafish Identifies Cilia Genes as a Principal Cause of Cystic Kidney Development. Development (Cambridge, England). 131(16):4085-4093
Golling, G., Amsterdam, A., Sun, Z., Antonelli, M., Maldonado, E., Chen, W., Burgess, S., Haldi, M., Artzt, K., Farrington, S., Lin, S.Y., Nissen, R.M., and Hopkins, N. (2002) Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development. Nature Genetics. 31(2):135-140
Sun, Z. and Hopkins, N. (2001) vhnf1, the MODY5 and familial GCKD-associated gene, regulates regional specification of the zebrafish gut, pronephros, and hindbrain. Genes & Development. 15(23):3217-3229
Amsterdam, A., Burgess, S., Golling, G., Chen, W., Sun, Z., Townsend, K., Farrington, S., Haldi, M., and Hopkins, N. (1999) A large-scale insertional mutagenesis screen in zebrafish. Genes & Development. 13(20):2713-2724