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.

Lead Principal Investigator
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Jianyi (Jay) Zhang, M.D., Ph.D. University of Alabama heart, left ventricular remodeling, myocardial energetics
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Nenad Bursac, PhD Duke University
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Timothy Kamp, M.D., Ph.D. University of Wisconsin-Madison
Post-Doctoral Fellow/Trainee
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Ling Gao Ph.D. University of Alabama at Birmingham
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Sajina GC UAB
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Abbi Helfer UAB
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Asher Krell University of Alabama at Birmingham
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Rachel University of Alabama at Birmingham
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Thanh Nguyen, PhD UAB
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Yasin Oduk Ph.D University of Alabama at Birmingham
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Eric Zhang, PhD University of Alabama
Administrative Coordinator
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Christina Crowe, MA UAB
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Kelly Hillard UAB
Affiliated Investigator
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Anton V Borovjagin M.Sc., Ph.D University of Alabama at Birmingham
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Ying Ge, Ph.D. Department of Cell and Regenerative Biology Department of Chemistry Director of Mass Spectrometry Human Proteomics Program University of Wisconsin-Madison
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Yuji Nakada, Ph.D. UAB
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Gangjian Qin, MD University of Alabama at Birmingham
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NS Rajasekaran The University of Alabama at Birmingham
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Rajasekaran Namakkal UAB
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Lei Ye, MD UAB
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Jianhua Zhang Ph.D. University of Wisconsin-Madison
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Yang Zhou, PhD University of Alabama
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Wuqiang Zhu M.D. Ph.D. University of Alabama at Birmingham
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
Jianyi (Jay) Zhang, Ling Gao, Zachery Gregorich, Wuqiang Zhu, and colleagues Large Cardiac-Muscle Patches Engineered from Human Induced-Pluripotent Stem-Cell–Derived Cardiac Cells Improve Recovery from Myocardial Infarction in Swine view
Cardiopatch Platform Enables Maturation and Scale-up of Human Pluripotent Stem Cell-derived Engineered Heart Tissues view
Timothy Kamp, Pratik Lalit, Adriana Rodriguez, and Karen Downs Generation of multipotent induced cardiac progenitor cells from mouse fibroblasts and potency testing in ex vivo mouse embryos view

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