CHANG Chiayu Alex
Professor, Principal Investigator
Research direction：aging in genetic cardiomyopathy; mechanotransduction in diseased cardiomyocytes; anti-aging drug development
E-mail：alexchang@@shsmu.edu.cn
Lab: http://www.shipm.cn/jyjz_web/html/jyjz_English/jyjz_eg_zjs_sysjj/List/index.htm
Research Interests
With the rapid aging population, increase in disease incidence associated with aging is a major challenge for the healthcare system. Aging is the biggest risk factor in cardiovascular disease, but the underlying mechanisms remain to be elucidated. The Chang Lab uses clinical samples, mouse models, human induced pluripotent stem cell (hiPSC) derived cardiomyocytes and traction force microscopy to interrogate the molecular connection between aging and heart failure. The lab is set to establish a hiPSC biobank that integrates next generation sequence to propel translational research.
Education and Work Experience
2001-2006 B.Sc. in Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
2006-2012 Ph.D. in Experimental Medicine, University of British Columbia, Vancouver, Canada
2012-2016 Postdoctoral Fellow, Baxter Laboratory, School of Medicine, Stanford University, USA
2017-2018 Instructor, Baxter Laboratory and Department of Cardiology, School of Medicine, Stanford University, USA
2018-present Professor, Principal Investigator, Shanghai Institute of Precision Medicine and Department of Cardiology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China
Selected Publications
Omer AD, Zago M, Chang A, Dennis PP*. Probing the structure and function of an archaeal C/D-box methylation guide sRNA. RNA. 12(9):1708-1720.
Fu Y, Chang A, Chang L, Niessen K, Eapen S, Setiadi A, and Karsan A*. Differential regulation of TGFbeta signaling pathways by notch in human endothelial cells. J Biol Chem 284(29): 19452-62.
Vrljicak P, Chang AC, Morozova O, Wederell ED, Niessen K, Marra MA, Karsan A and Hoodless PA*. Genomic Analysis Distinguishes Phases of Early Development of the Mouse Atrio-Ventricular Canal. Physiological Genomics 40(3): 150-7.
Fu Y#, Chang AC#, Fournier M, Chang L, Niessen K, and Karsan A*. RUNX3 maintains the mesenchymal phenotype after termination of the notch signal. (*co-author). J Biol Chem 286(13): 11803-13.
Chang AC, Fu YX, Garside VC, Niessen K, Chang L, Fuller M, Setiadi A, Smrz J, Kyle A, Minchinton A, Marra M, Hoodless P, and Karsan A*. Notch initiates the endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble guanylyl cyclase. Developmental Cell 21(2): 288-300.
Vrljicak P, Cullum R, Xu E, Chang AC, Wederell ED, Bilenky M, Jones SJ, Marra MA, Karsan A and Hoodless PA*. Twist1 transcriptional targets in the developing atrio-ventricular canal of the mouse. PLoS One 7(7):e40815.
Garside VC, Chang AC, Karsan A and Hoodless PA*. Co-ordinating Notch, BMP, and TGFβ Signalling During Heart Valve Development. Cellular and Molecular Life Sciences 70(16):2899-917.
Chang AC, Patenaude A, Lu K, Fuller M, Ly M, Kyle A, Golbidi S, Wang Y, Walley K, Minchinton A, Laher I, Karsan A*. Notch-Dependent Regulation of the Ischemic Vasodilatory Response. Arterioscler Thromb Vasc Biol. 33(3):510-2.
El-Sehemy A, Chang A, Azad AK, Gupta N, Xu Z, Steed H, Karsan A, Fu Y*. Notch activation augments nitric oxide/soluble guanylyl cyclase signaling in immortalized ovarian surface epithelial cells and ovarian cancer cells. Cell Signal. 25(12):2780-7.
Chang AC, Garside VC, Fournier M, Smrz J, Vrljicak P, Umlandt P, Fuller M, Robertson G, Zhao Y, Tam A, Jones SJ, Marra MA, Hoodless PA, Karsan A*. A Notch-dependent transcriptional hierarchy promotes mesenchymal transdifferentiation in the cardiac cushion. Dev Dyn. 243(7): 894-905.
Burridge PW, Li YF, Matsa E, Wu H, Ong S-G, Sharma A, Holmstrom A, Chang AC, Coronado MJ, Ebert AD, Knowles JW, Telli ML, Witteles RM, Blau HM, Bernstein D, Altman RB and Wu JC*. Human induced pluripotent stem cell-derived cardiomyocytes recapulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity. Nature Medicine 22(5):547-56. PMCID: PMC5086256
Chang AC, Ong SG, LaGory E, Kraft P, Giaccia AJ, Wu JC, Blau HM*. Telomere shortening and metabolic compromise underlie dystrophic cardiomyopathy. Proc Natl Acad Sci U S A. 113(46): 13120-13125. PMID: 27799523.
Yucel N, Chang AC, Day JW, Rosenthal N, Blau HM*. Humanizing the mdx mouse model of DMD: the long and the short of it. npj Regenerative Medicine. 2018 Feb 16,3:4. PMID: 29479480 PMCID: PMC5816599.
Chang AC* and Blau HM*. Short Telomeres - A Hallmark of Heritable Cardiomyopathies. Differentiation 100:31-36. PMID: 29482077 PMCID: PMC5889329.
Parikh VN, Liu J, Shang C, Woods C, Chang AC, Zhao M, Charo DN, Grunwald Z, Huang Y, Seo K, Tsao PS, Bernstein D, Ruiz-Lozano P, Quertermous T, and Ashley EA*. (2018) Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition. American Journal of Physiology-Heart and Circulatory Physiology 315(2):H348-H356. PMID: 29775410.
Chang ACY*, Chang ACH, Kirillova A, Sasagawa K, Su W, Weber G, Lin J, Termglinchan V, Karakikes I, Seeger T, Dainis AM, Hinson JT, Seidman J, Seidman CE, Day JW, Ashley E, Wu JC, and Blau HM*. (2018) Telomere shortening is a hallmark of genetic cardiomyopathies. Proc Natl Acad Sci U S A. 115(37): 9276-9281. PMID: 30150400
Chang ACY*, Chang ACH, Nicin L, Weber GJ, Holbrook C, Davis MF, Blau HM, and Bertaccini EJ*. An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics. Anesth Analg 2020 Jan,130(1):e1-e4. PMID: 30198930
Zhang JZ, Termglinchan V, Shao NY, Itzhaki I, Liu C, Ma N, Tian L, Wang VY, Chang ACY, Guo H, Kitani T, Wu H, Lam CK, Kodo K, Sayed N, Blau HM, Wu JC*. A Human iPSC Double-Reporter System Enables Purification of Cardiac Lineage Subpopulations with Distinct Function and Drug Response Profiles. Cell Stem Cell. 2019 May 2,24(5):802-811.
Wu H, Yang H, Rhee JW, Zhang JZ, Lam CK, Sallam K, Chang ACY, Ma N, Lee J, Zhang H, Blau H, Bers DM, and Wu JC*. Modelling diastolic dysfunction in induced pluripotent stem cell-derived cardiomyocytes from hypertrophic cardiomyopathy patients. Eur Heart Journal. 2019 Dec 1,40(45):3685-3695.
Cordero P, Parikh VN, Chin ET, Erbilgin A, Gloudemans MJ, Shang C, Huang Y, Chang AC, Smith KS, Dewey F, Zaleta K, Morley M, Brandimarto J, Glazer N, Waggott D, Pavlovic A, Zhao M, Moravec CS, Tang WHW, Skreen J, Malloy C, Hannenhalli S, Li H, Ritter S, Li M, Bernstein D, Connolly A, Hakonarson H, Lusis AJ, Margulies KB, Depaoli-Roach AA, Montgomery SB, Wheeler MT, Cappola T, Ashley EA*. Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure. Nat Commun. 2019 Jun 24,10(1):2760. doi: 10.1038/s41467-019-10591-5.
LaRocca TJ , Seeger T, Prado M , Perea-Gil I, Neofytou E, Mecham BH, Ameen M, Chang ACY, Pandey G, Wu JC, Karakikes I*. Pharmacological Silencing of MicroRNA-152 Prevents Pressure Overload-Induced Heart Failure. Circ Heart Fail. 2020 Mar,13(3):e006298. doi: 10.1161/CIRCHEARTFAILURE.119.006298. Epub 2020 Mar 12.
Dainis A, Zaleta-Rivera K, Ribeiro A, Chang ACH, Shang C, Lan F, Burridge PW, Liu WR, Wu JC, Chang ACY, Pruitt BL, Wheeler M, Ashley E*. Silencing of MYH7 ameliorates disease phenotypes in human iPSC-cardiomyocytes. Physiol Genomics. 2020 Jul 1,52(7):293-303. doi: 10.1152/physiolgenomics.00021.2020. Epub 2020 Jun 22.
Li B, Xiong W, Liang WM, Chiou JS, Lin YJ, Chang ACY*. Targeting of CAT and VCAM1 as Novel Therapeutic Targets for DMD Cardiomyopathy. Front Cell Dev Biol. 2021 Apr 1,9:659177. doi: 10.3389/fcell.2021.659177
Chang ACY*, Pardon G, Chang ACH, Wu H, Ong SG, Eguchi A, Ancel S, Holbrook C, Ramunas J, Ribeiro AJS, LaGory EL, Wang H, Koleckar K, Giaccia A, Mack DL, Childers MK, Denning C, Day JW, Wu JC, Pruitt BL, and Blau HM*. Increased Tissue Stiffness Triggers Contractile Dysfunction and Telomere Shortening in Dystrophic Cardiomyocytes. Stem Cell Reports. 2021 June in press.
