Zhang (UAB) Research Hub 07

Jianyi “Jay” Zhang, MD, PhD

U01 Principal Investigator, 1-U01HL134764-01

Integrated Cellular and Tissue Engineering for Ischemic Heart Disease

Ischemic heart disease continues to have a tremendous impact on public health, shortening lifespan and impairing the quality of life. The inability of the adult human myocardium to undergo regeneration after a myocardial infarction has inspired research using cell therapy for myocardial repair. However, clinical trials to date have shown modest or no benefit, suggesting the need to consider other cell sources and approaches. In large animal models, derivatives of human pluripotent stem cells have provided promising results, but the grafts have generally been small, transient, and of limited functional benefit. In addition, there remain important questions regarding cardiac cells derived from iPSCs, including the optimal delivery strategy, immunogenicity, maturity, and the ability to couple effectively to the native myocardium without causing arrhythmias. In this proposal, three integrated projects will address these challenges and advance toward the long-term goal of utilizing a functional human cardiac tissue patch (hCTP) for repair of ischemic myocardium. The first project aims to generate novel cell populations, including induced cardiac progenitor cells and genetically engineered cell lines that will be evaluated for their immunogenicity in a novel humanized mouse model. These and other cell products, including commercially available sources, will be utilized to generate large vascularized hCTPs in the second project. The third project will utilize a porcine post-infarction model to test hCTPs and optimize electrical and vascular integration as assessed by optical mapping technology and MRI/NMR spectroscopy, respectively. These studies will overcome critical barriers to generating large, fully functional human cardiac tissues that can be integrated safely into the native myocardium to provide a powerful new approach for treatment of advanced ischemic heart disease.

members: 
Lead Principal Investigator
User Name Full Name Institute Affiliation Topic tags People tags
jzhang's picture
jzhang Jianyi (Jay) Zhang, M.D., Ph.D. University of Alabama heart, left ventricular remodeling, myocardial energetics
Co-PI/Co-Investigator
User Name Full Name Institute Affiliation Topic tags People tags
nbursac's picture
nbursac Nenad Bursac, PhD Duke University
tkamp's picture
tkamp Timothy Kamp, M.D., Ph.D. University of Wisconsin-Madison
Post-Doctoral Fellow/Trainee
User Name Full Name Institute Affiliation Topic tags People tags
lAgao's picture
lAgao Ling Gao Ph.D. University of Alabama at Birmingham
sajinagc's picture
sajinagc Sajina GC UAB
ahelfer's picture
ahelfer Abbi Helfer UAB
AAkrell's picture
AAkrell Asher Krell University of Alabama at Birmingham
YAoduk's picture
YAoduk Yasin Oduk Ph.D University of Alabama at Birmingham
ezhang's picture
ezhang Eric Zhang, PhD University of Alabama
Administrative Coordinator
User Name Full Name Institute Affiliation Topic tags People tags
ccrowe's picture
ccrowe Christina Crowe, MA UAB
kellyh's picture
kellyh Kelly Hillard UAB
Affiliated Investigator
User Name Full Name Institute Affiliation Topic tags People tags
AAborovjagin's picture
AAborovjagin Anton V Borovjagin M.Sc., Ph.D University of Alabama at Birmingham
yingge's picture
yingge Ying Ge, Ph.D. Department of Cell and Regenerative Biology Department of Chemistry Director of Mass Spectrometry Human Proteomics Program University of Wisconsin-Madison
ynakada's picture
ynakada Yuji Nakada, Ph.D. UAB
gqin's picture
gqin Gangjian Qin, MD University of Alabama at Birmingham
Lei Ye's picture
Lei Ye Lei Ye, MD UAB
JianZhang's picture
JianZhang Jianhua Zhang Ph.D. University of Wisconsin-Madison
yzhou's picture
yzhou Yang Zhou, PhD University of Alabama
WuqiZhu's picture
WuqiZhu Wuqiang Zhu M.D. Ph.D. University of Alabama at Birmingham
Publication: 
Author(s) Title Link
Patil M, Saheera S, Dubey PK, Kahn-Krell A, Kumar GP et al Novel Mechanisms of Exosome-Mediated Phagocytosis of Dead Cells in Injured Heart view
Zhao M, Nakada Y, Wei Y, Bian W, Chu Y, Borovjagin AV et al Cyclin D2 Overexpression Enhances the Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Repair in a Swine Model of Myocardial Infarction view
Fan C, Tang Y, Zhao M, Lou X, Pretorius D, Menasche P et al CHIR99021 and Fibroblast Growth Factor 1 Enhance the Regenerative Potency of Human Cardiac Muscle Patch After Myocardial Infarction in Mice view
Zhang L, Tian L, Dai X, Yu H, Wang J, Lei A et al Pluripotent Stem Cell-Derived CAR-Macrophage Cells with Antigen-Dependent Anti-Cancer Cell Functions view
Kamdar F, Das S, Gong W, Klaassen KA, Meyers TA, Shah P et al Stem Cell-Derived Cardiomyocytes and Beta-Adrenergic Receptor Blockade in Duchenne Muscular Dystrophy Cardiomyopathy view
Saidulu Mattapally, Kevin M. Pawlik, Vladimir G. Fast, Esther Zumaquero, Frances E. Lund, Troy D. Randall, Tim M. Townes, Jianyi Zhang Human Leukocyte Antigen Class I and II Knockout Human Induced Pluripotent Stem Cell–Derived Cells: Universal Donor for Cell Therapy view
Ngan F. Huang, Vahid Serpooshan, Viola B. Morris, Nazish Sayed, Gaspard Pardon, Oscar J. Abilez, Karina H. Nakayama, Beth L. Pruitt, Sean M. Wu, Young-sup Yoon, Jianyi Zhang & Joseph C. Wu Big Bottlenecks in Cardiovascular Tissue Engineering view
Jianyi Zhang, E. Dale Abel Effective Metabolic Approaches for the Energy Starved Failing Heart view
Jianyi Zhang, Wuqiang Zhu, Milica Radisic, and Gordana Vunjak-Novakovic Can We Engineer a Human Cardiac Patch for Therapy? view
CCND2 Overexpression Enhances the Regenerative Potency of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Remuscularization of Injured Ventricle view

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