The cardiovascular system is the first functioning organ during development. Abnormalities in the formation and/or function of the heart and vessels often lead to embryonic lethality or cause severe health issues in the adult. Our laboratory uses a multidisciplinary approach and the zebrafish model to understand the genetic, molecular and cellular basis of the cardiovascular system during normal development and in diseases.
Several unique features make zebrafish ideal for genetic and embryological studies. For instance, the transparent nature of zebrafish embryos provides easy access to observe and study organ development in live embryos. From classic and chemical genetic screens, we have identified mutations and compounds that affect proper patterning or function of the heart and vessels in the zebrafish. We are now using these mutants and compounds as points of entry to study questions about (1) molecular hierarchies important for the formation and cardiac progenitor cells; (2) molecular and cellular mechanisms for cardiac chamber maturation; (3) molecular and physiological mechanisms by which rhythmic cardiac contraction is maintained and by which cardiac arrhythmia occurs.
Xu Q, Dupper N, Smaligo A, Fan, YC, Cai L,Wang Z, Langenbacher A, Chen J-N and Kwon O., "Catalytic Enantioselective Synthesis of Guvacine Derivatives Through [4 + 2] Annulations of Imines With ?-Methylallenoates", Organic Letters 20 (19): 6089-6093 (2018).
Ding Y, Ma J, Langenbacher AD, Baek KI, Lee J, Chang CC, Hsu JJ, Kulkarni RP, Belperio J, Shi W, Ranjbarvaziri S, Ardehali R, Tintut Y, Demer LL, Chen JN, Fei P, Packard RRS, Hsiai TK., "Multiscale lightsheet for rapid imaging of cardiopulmonary system", JCI Insight 3 (16): 1-14 (2018).
Ziyad S, Riordan JD, Cavanaugh AM, Su T, Hernandez GE, Hilfenhaus G, Morselli M, Huynh K, Wang K, Chen JN, Dupuy AJ and Iruela-Arispe ML., "A forward genetic screen targeting the endothelium reveals a regulatory role for the lipid kinase Pi4ka in myelo-and erythropoiesis", Cell Reports 22: 1211-1224 (2018).
Shimizu H, Langenbacher AD, Huang J, Wang K, Otto G, Geisler R, Wang Y, Chen JN., "The Calcineurin-FoxO-MuRF1 signaling pathway regulates myofibril integrity in cardiomyocytes", eLife 6 (e27955): 1-19 (2017).
Lu F, Langenbacher AD and Chen JN, "Tbx20 drives cardiac progenitor formation and cardiac proliferation in zebrafish", Developmental Biology 421: 139-148 (2017).
Berchtold MW, Kulej K, Zacharias T, Wang K, Torggler RF, Lorentzen L, Jespersen T, Chen JN, Larsen MR and La Cour JM, "The Arrhythmogenic Calmodulin Mutation D129G Dysregulates Cell Growth, Calmodulin-dependent Kinase II Activity and Cardiac Function in Zebrafish", J. Biol Chem 291: 26636-26646 (2016).
Lu F, Langenbacher AD and Chen JN, "Transcriptional Regulation of Heart Development in Zebrafish", J. Cardiovasc Dev Dis 3 (14): (2016).
Gao C, Ren S, Lee J-H, Qiu J, Chapski D, Rau C, Zhou Y, Abdellatif M, Nakano A, Vondriska T, Xiao X, Fu X-D, Chen JN and Wang Y, "RBFox1 Mediated RNA Splicing Regulates Cardiac Hypertrophy and Heart Failure", J. Clin. Invest 126: 195-206 (2015).
Cavanaugh A, Huang J and Chen JN, "Two developmentally distinct populations of neural crest cells contribute to the zebrafish heart", Developmental Biology 404: 103-112 (2015).
Shimizu H*, Schredelseker J*, Huang J*, Lu K*, Naghdi S, Lu F, Franklin S, Fiji HDG, Wang K, Zhu H, Cheng T, Lin B, Nakano H, Nakai J, Stieg AZ, Gimzewski JK, Nakano A, Goldhaber JI,Vondriska TM, Hajnóczky G, Kwon O and Chen JN, "Activation of VDAC2 modulates mitochondrial Ca2+ uptake and cardiac rhythmicity", eLife 4 (e04801): 1-20 (2015).
Lin C, Yao E, Wang K, Nozawa Y, Shimizu H, Johnson J, Chen JN, Krogan N, Chuang PT., "Regulation of Sufu activity by p66b and mycbp provides new insights into vertebrate hedgehog signaling", Genes and Development 28: 2547-2563 (2014).
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 JN, Line CL, Chi NC, Hsiai TK, "Shear stress-activated Wnt-angiopoietin-2 signaling recapitulated vascular repair in zebrafish embryos", Arterioscler Thromb Vasc Biol 34: 2268-2275 (2014).
Zhang Y, Shimizu H, Siu KL, Mahajan A, Chen JN and Cai H, "NADPH oxidase 4 induces cardiac arrhythmic phenotype in zebrafish", J. Biol Chem 289: 23200-23208 (2014).
Schredelseker J, Paz A, Lopez CJ, Altenbach C, Leung CS, Drexler MK, Chen JN, Hubbell WL, Abramson J., "High resolution structure and double electron-electron resonance of the zebrafish voltage-dependent anion channel 2 reveal an oligomeric population", J Biol Chem 289: 12566-12577 (2014).
Monte E, Mouillesseaux K, Chen H, Kimball T, Ren S, Wang Y, Chen JN, Vondriska TM, Franklin S., "Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of growth and cellular plasticity in cardiomyocytes", Am J Physiology 305: 1624-1638 (2013).