ZFIN ID: ZDB-LAB-111129-2
Neil C. Chi Lab
PI/Director: Chi, Neil C.
Contact Person:
Address: UCSD School of Medicine 9500 Gilman Dr, Mail Code 0613-J La Jolla CA 92093-0613
Country: United States
Fax: 858-534-0522
Line Designation: sd

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Cardiovascular diseases, such as heart failure and stroke, are the leading cause of morbidity and mortality in the US and developed world due to failure to adequately replace lost myocardium and promote vasculogenesis/angiogenesis for supplying blood and oxygen to ischemic tissue. Though recent studies support the existence of a common progenitor for the cardiac and vascular lineages, the underlying developmental cues and transcriptional/epigenetic networks responsible for specification of these cell fates remain unclear. Our laboratory uses cellular, molecular, genetic, and transgenic approaches to study the specification, patterning, and differentiation of these cardiovascular progenitor cells that give rise to the heart and the vascular system.

Han, Peidong Post-Doc Han, Sangyoon Post-Doc Perry, Cynthia N. Post-Doc
Yang, Hongbo Post-Doc Deacon, Dekker Graduate Student Grinstein, Jonathan Graduate Student
Tedeschi, Gary Neil Research Staff Dickover, Michael Technical Staff Hegarty, Jeff Technical Staff
Gregory, Diana Perry Administrative Staff

Ross, K.D., Ren, J., Zhang, R., Chi, N.C., Hamilton, B.A. (2021) Ankfn1-mutant vestibular defects require loss of both ancestral and derived paralogs for penetrance in zebrafish. G3 (Bethesda). 12(3):
Sidhwani, P., Leerberg, D.M., Boezio, G.L.M., Capasso, T.L., Yang, H., Chi, N.C., Roman, B.L., Stainier, D.Y.R., Yelon, D. (2020) Cardiac function modulates endocardial cell dynamics to shape the cardiac outflow tract. Development (Cambridge, England). 147(12):
Ren, J., Han, P., Ma, X., Farah, E.N., Bloomekatz, J., Zeng, X.I., Zhang, R., Swim, M.M., Witty, A.D., Knight, H.G., Deshpande, R., Xu, W., Yelon, D., Chen, S., Chi, N.C. (2019) Canonical Wnt5b Signaling Directs Outlying Nkx2.5+ Mesoderm into Pacemaker Cardiomyocytes. Developmental Cell. 50(6):729-743.e5
Gálvez-Santisteban, M., Chen, D., Zhang, R., Serrano, R., Nguyen, C., Zhao, L., Nerb, L., Masutani, E.M., Vermot, J., Burns, C.G., Burns, C.E., Del Álamo, J.C., Chi, N.C. (2019) Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming. eLIFE. 8:
Takada, N., Omae, M., Sagawa, F., Chi, N.C., Endo, S., Kozawa, S., Sato, T.N. (2017) Re-evaluating functional landscape of the cardiovascular system during development. Biology Open. 6(11):1756-1770
Hu, Z., Liu, Y., Huarng, M.C., Menegatti, M., Reyon, D., Rost, M.S., Norris, Z.G., Richter, C.E., Stapleton, A.N., Chi, N.C., Peyvandi, F., Joung, J.K., Shavit, J.A. (2017) Genome editing of factor X in zebrafish reveals unexpected tolerance of severe defects in the common pathway. Blood. 130(5):666-676
Pradhan, A., Zeng, X.I., Sidhwani, P., Marques, S.R., George, V., Targoff, K.L., Chi, N.C., Yelon, D. (2017) FGF signaling enforces cardiac chamber identity in the developing ventricle. Development (Cambridge, England). 144(7):1328-1338
Lardelli, R.M., Schaffer, A.E., Eggens, V.R., Zaki, M.S., Grainger, S., Sathe, S., Van Nostrand, E.L., Schlachetzki, Z., Rosti, B., Akizu, N., Scott, E., Silhavy, J.L., Heckman, L.D., Rosti, R.O., Dikoglu, E., Gregor, A., Guemez-Gamboa, A., Musaev, D., Mande, R., Widjaja, A., Shaw, T.L., Markmiller, S., Marin-Valencia, I., Davies, J.H., de Meirleir, L., Kayserili, H., Altunoglu, U., Freckmann, M.L., Warwick, L., Chitayat, D., Blaser, S., Çağlayan, A.O., Bilguvar, K., Per, H., Fagerberg, C., Christesen, H.T., Kibaek, M., Aldinger, K.A., Manchester, D., Matsumoto, N., Muramatsu, K., Saitsu, H., Shiina, M., Ogata, K., Foulds, N., Dobyns, W.B., Chi, N.C., Traver, D., Spaccini, L., Bova, S.M., Gabriel, S.B., Gunel, M., Valente, E.M., Nassogne, M.C., Bennett, E.J., Yeo, G.W., Baas, F., Lykke-Andersen, J., Gleeson, J.G. (2017) Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing. Nature Genetics. 49(3):457-464
Bloomekatz, J., Galvez-Santisteban, M., Chi, N.C. (2016) Myocardial plasticity: cardiac development, regeneration and disease. Current opinion in genetics & development. 40:120-130
Reischauer, S., Stone, O.A., Villasenor, A., Chi, N., Jin, S.W., Martin, M., Lee, M.T., Fukuda, N., Marass, M., Witty, A., Fiddes, I., Kuo, T., Chung, W.S., Salek, S., Lerrigo, R., Alsiö, J., Luo, S., Tworus, D., Augustine, S.M., Mucenieks, S., Nystedt, B., Giraldez, A.J., Schroth, G.P., Andersson, O., Stainier, D.Y. (2016) Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification. Nature. 535:294-8
Han, P., Bloomekatz, J., Ren, J., Zhang, R., Grinstein, J.D., Zhao, L., Burns, C.G., Burns, C.E., Anderson, R.M., Chi, N.C. (2016) Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis. Nature. 534:700-4
Lee, J., Fei, P., Packard, R.R., Kang, H., Xu, H., Baek, K.I., Jen, N., Chen, J., Yen, H., Kuo, C.J., Chi, N.C., Ho, C.M., Li, R., Hsiai, T.K. (2016) 4-Dimensional light-sheet microscopy to elucidate shear stress modulation of cardiac trabeculation. The Journal of Clinical Investigation. 126(5):1679-90
Yang, H., Fang, L., Zhan, R., Hegarty, J.M., Ren, J., Hsiai, T.K., Gleeson, J.G., Miller, Y.I., Trejo, J., Chi, N.C. (2015) Polo-like kinase 2 regulates angiogenic sprouting and blood vessel development. Developmental Biology. 404(2):49-60
Zhang, M., Sun, T., Jian, C., Lei, L., Han, P., Lv, Q., Yang, R., Zhou, X., Xu, J., Hu, Y., Men, Y., Huang, Y., Zhang, C., Zhu, X., Wang, X., Cheng, H., Xiong, J.W. (2015) Remodeling of Mitochondrial Flashes in Muscular Development and Dystrophy in Zebrafish. PLoS One. 10:e0132567
Guemez-Gamboa, A., Nguyen, L.N., Yang, H., Zaki, M.S., Kara, M., Ben-Omran, T., Akizu, N., Rosti, R.O., Rosti, B., Scott, E., Schroth, J., Copeland, B., Vaux, K.K., Cazenave-Gassiot, A., Quek, D.Q., Wong, B.H., Tan, B.C., Wenk, M.R., Gunel, M., Gabriel, S., Chi, N.C., Silver, D.L., Gleeson, J.G. (2015) Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. Nature Genetics. 47(7):809-13
Kametani, Y., Chi, N.C., Stainier, D.Y., Takada, S. (2015) Notch signaling regulates venous arterialization during zebrafish fin regeneration. Genes to cells : devoted to molecular & cellular mechanisms. 20(5):427-38
Mishra-Gorur, K., Çağlayan, A.O., Schaffer, A.E., Chabu, C., Henegariu, O., Vonhoff, F., Akgümüş, G.T., Nishimura, S., Han, W., Tu, S., Baran, B., Gümüş, H., Dilber, C., Zaki, M.S., Hossni, H.A., Rivière, J., Kayserili, H., Spencer, E.G., Rosti, R.Ö., Schroth, J., Per, H., Çağlar, C., Çağlar, Ç., Dölen, D., Baranoski, J.F., Kumandaş, S., Minja, F.J., Erson-Omay, E.Z., Mane, S.M., Lifton, R.P., Xu, T., Keshishian, H., Dobyns, W.B., Chi, N.C., Šestan, N., Louvi, A., Bilgüvar, K., Yasuno, K., Gleeson, J.G., Günel, M. (2014) Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors. Neuron. 84:1226-1239
Li, R., Beebe, T., Jen, N., Yu, F., Takabe, W., Harrison, M., Cao, H., Lee, J., Yang, H., Han, P., Wang, K., Shimizu, H., Chen, J., Lien, C.L., Chi, N.C., Hsiai, T.K. (2014) Shear Stress-Activated Wnt-Angiopoietin-2 Signaling Recapitulates Vascular Repair in Zebrafish Embryos. Arterioscler. Thromb. Vasc. Biol.. 34(10):2268-75
Han, P., Zhou, X.H., Chang, N., Xiao, C.L., Yan, S., Ren, H., Yang, X.Z., Zhang, M.L., Wu, Q., Tang, B., Diao, J.P., Zhu, X., Zhang, C., Li, C.Y., Cheng, H., Xiong, J.W. (2014) Hydrogen peroxide primes heart regeneration with a derepression mechanism. Cell Research. 24(9):1091-107
Yan, B., Han, P., Pan, L., Lu, W., Xiong, J., Zhang, M., Zhang, W., Li, L., Wen, Z. (2014) Il-1beta and Reactive Oxygen Species Differentially Regulate Neutrophil Directional Migration and Basal Random Motility in a Zebrafish Injury-Induced Inflammation Model. Journal of immunology (Baltimore, Md. : 1950). 192(12):5998-6008
Dickover, M., Hegarty, J.M., Ly, K., Lopez, D., Yang, H., Zhang, R., Tedeschi, N., Hsiai, T.K., Chi, N.C. (2014) The atypical Rho GTPase, RhoU, regulates cell-adhesion molecules during cardiac morphogenesis. Developmental Biology. 389:182-91
Samson, S.C., Ferrer, T., Jou, C.J., Sachse, F.B., Shankaran, S.S., Shaw, R.M., Chi, N.C., Tristani-Firouzi, M., and Yost, H.J. (2013) 3-OST-7 regulates BMP-dependent cardiac contraction. PLoS Biology. 11(12):e1001727
Lee, J., Moghadam, M.E., Kung, E., Cao, H., Beebe, T., Miller, Y., Roman, B.L., Lien, C.L., Chi, N.C., Marsden, A.L., and Hsiai, T.K. (2013) Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis. PLoS One. 8(8):e72924
Page, D.M., Wittamer, V., Bertrand, J.Y., Lewis, K.L., Pratt, D.N., Delgado, N., Schale, S.E., McGue, C., Jacobsen, B.H., Doty, A., Pao, Y., Yang, H., Chi, N.C., Magor, B.G., and Traver, D. (2013) An evolutionarily conserved program of B cell development and activation in zebrafish. Blood. 122(8):e1-e11
Zhang, R., Han, P., Yang, H., Ouyang, K., Lee, D., Lin, Y.F., Ocorr, K., Kang, G., Chen, J., Stainier, D.Y., Yelon, D., and Chi, N.C. (2013) In vivo cardiac reprogramming contributes to zebrafish heart regeneration. Nature. 498(7455):497-501
Hegarty, J.M., Yang, H., and Chi, N.C. (2013) UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development. Development (Cambridge, England). 140(8):1713-1719
Dickover, M.S., Zhang, R., Han, P., and Chi, N.C. (2013) Zebrafish cardiac injury and regeneration models: a noninvasive and invasive in vivo model of cardiac regeneration. Methods in molecular biology (Clifton, N.J.). 1037:463-473
Tu, S., and Chi, N.C. (2012) Zebrafish models in cardiac development and congenital heart birth defects. Differentiation; research in biological diversity. 84(1):4-16
Hong, T.T., Smyth, J.W., Chu, K.Y., Vogan, J.M., Fong, T.S., Jensen, B.C., Fang, K., Halushka, M.K., Russell, S.D., Colecraft, H., Hoopes, C.W., Ocorr, K., Chi, N.C., and Shaw, R.M. (2012) BIN1 is Reduced and Cav1.2 Trafficking is Impaired in Human Failing Cardiomyocytes. Heart rhythm. 9(5):812-820
Yu, F., Zhao, Y., Gu, J., Quigley, K.L., Chi, N.C., Tai, Y.C., and Hsiai, T.K. (2012) Flexible microelectrode arrays to interface epicardial electrical signals with intracardial calcium transients in zebrafish hearts. Biomedical Microdevices. 14(2):357-366
Yoruk, B., Gillers, B.S., Chi, N.C., and Scott, I.C. (2012) Ccm3 functions in a manner distinct from Ccm1 and Ccm2 in a zebrafish model of CCM vascular disease. Developmental Biology. 362(2):121-131
Chi, N.C., Bussen, M., Brand-Arzamendi, K., Ding, C., Olgin, J.E., Shaw, R.M., Martin, G.R., and Stainier, D.Y. (2010) Cardiac conduction is required to preserve cardiac chamber morphology. Proceedings of the National Academy of Sciences of the United States of America. 107(33):14662-14667
Deacon, D.C., Nevis, K.R., Cashman, T.J., Zhou, Y., Zhao, L., Washko, D., Guner-Ataman, B., Burns, C.G., and Burns, C.E. (2010) The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis. Development (Cambridge, England). 137(11):1887-1896
Bertrand, J.Y., Chi, N.C., Santoso, B., Teng, S., Stainier, D.Y., and Traver, D. (2010) Haematopoietic stem cells derive directly from aortic endothelium during development. Nature. 464(7285):108-111
Smyth, J.W., Hong, T.T., Gao, D., Vogan, J.M., Jensen, B.C., Fong, T.S., Simpson, P.C., Stainier, D.Y., Chi, N.C., and Shaw, R.M. (2010) Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium. J. Clin. Invest.. 120(1):266-279
Anderson, R.M., Bosch, J.A., Goll, M.G., Hesselson, D., Dong, P.D., Shin, D., Chi, N.C., Shin, C.H., Schlegel, A., Halpern, M., and Stainier, D.Y. (2009) Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration. Developmental Biology. 334(1):213-223
De Val, S., Chi, N.C., Meadows, S.M., Minovitsky, S., Anderson, J.P., Harris, I.S., Ehlers, M.L., Agarwal, P., Visel, A., Xu, S.M., Pennacchio, L.A., Dubchak, I., Krieg, P.A., Stainier, D.Y., and Black, B.L. (2008) Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors. Cell. 135(6):1053-1064
Chi, N.C., Shaw, R.M., Jungblut, B., Huisken, J., Ferrer, T., Arnaout, R., Scott, I., Beis, D., Xiao, T., Baier, H., Jan, L.Y., Tristani-Firouzi, M., and Stainier, D.Y. (2008) Genetic and Physiologic Dissection of the Vertebrate Cardiac Conduction System. PLoS Biology. 6(5):e109
Chi, N.C., Shaw, R.M., De Val, S., Kang, G., Jan, L.Y., Black, B.L., and Stainier, D.Y. (2008) Foxn4 directly regulates tbx2b expression and atrioventricular canal formation. Genes & Development. 22(6):734-739
Arnaout, R., Ferrer, T., Huisken, J., Spitzer, K., Stainier, D.Y., Tristani-Firouzi, M., and Chi, N.C. (2007) Zebrafish model for human long QT syndrome. Proceedings of the National Academy of Sciences of the United States of America. 104(27):11316-11321
Jin, S.W., Herzog, W., Santoro, M.M., Mitchell, T.S., Frantsve, J., Jungblut, B., Beis, D., Scott, I.C., D'Amico, L.A., Ober, E.A., Verkade, H., Field, H.A., Chi, N.C., Wehman, A.M., Baier, H., and Stainier, D.Y. (2007) A transgene-assisted genetic screen identifies essential regulators of vascular development in vertebrate embryos. Developmental Biology. 307(1):29-42