The Zhang Laboratory:
Translational Cardiobiology Laboratory
Yiqiang Zhang, PhD
Department of Anatomy, Biochemistry, and Physiology
John A. Burns School of Medicine
University of Hawaii at Manoa
Center for Cardiovascular Research
John A. Burns School of Medicine
University of Hawaii at Manoa
Developmental and Reproductive Biology (DRB)
Cell and Molecualr Biology (CMB)
Phone: (808) 692-1480 (Office), 692-1611 (Lab)
Address: 651 Ilalo Street BSB-311D, Honolulu, HI 96813
Integrative Cellular Molecular Cardiobiology and Heart Regeneration
About our lab
The Translational Cardiobiology Laboratory focuses on major areas of disease-realted research, including heart failure, diabetes, and arrhythmias. Dr. Zhang and his team study cardiac and stem cell biology and heart regeneration, cardiac growth and disease mechanisms, cell cycle control, epigenetics and functional genomics, heart failure therapies, diabetic cardiocomplications, and electrophysiology and arrhythmias. By obtaining an in-depth understanding of mechanisms underlying cardiac develpment and disease processes, and endogenous and exogenous heart regeneration, we hope to develop novel and effective therapeutics to treat congestive and congenital heart diseases.
DESCRIPTION OF RESEARCH
Heart cell hemostasis undergo dynamic changes during development and in disease processes. Understanding the molecular and genetic pathways regulating cell lineage and functions is a crucial step in treating congenital and congestive heart diseases such as heart failure. Mammalian cardiomyocytes rapidly enter into a quiescent cell cycle state shortly after birth. Dr. Zhang’s group first demonstrated that adult cardiomyocytes (ACMs) retain substantial cellular plasticity, capable of remodeling called as “dedifferentiation”, and can become more primitive to re-enter the cell cycle to proliferate, contributing to the endogenous myocardial regeneration in post-injury hearts, albeit at a low level. In addition, cardiomyocytes derived from pluripotent stem cells are great models and unlimited resources for exogenous heart regeneration. Still, molecular epigenetic regulations on cardiac cell biology and functions remain largely undetermined. An integrative system investigation in cell and molecular cardiobiology will reshape the future of preventing and treating heart disease.
Goals And Approaches:
With the ultimate goal of treating degenerative heart diseases by promoting both endogenous and exogenous cardiac regeneration, the Zhang lab is working to determine the integrative cardiac and non-cardiac cellular processes and molecular pathways regulating cardiomyocyte differentiation, maturation, dedifferentiation, and cell cycle activities. His team uses state-of-the-art transgenic and reporter cells and animal models bridging to human health, cutting-edge multi-omics and bioinformatics approaches, together with advanced cellular, molecular, and bioengineering technologies.
Cardiomyocyte Growth, Dedifferentiation, and Cell Cycle Regulation
Based upon our early work in cardiomyocyte dedifferentiation, we have recently developed new multi-reporter transgenic mouse models for rigorous cardiomyocyte lineage tracing and real-time maturity (versus dedifferentiation) visualization. We continue studying molecular regulations of endogenous myocardial regeneration, namely cardiomyocyte dedifferentiation followed by proliferation, in post-injury (infarcted and hypertrophic) and metabolic stressed (diabetic) hearts.
Stem Cell and Cardiac Biology, Bioengineering, Cardiac Physiology, and Heart Regeneration
Pluripotent stem cells (e.g., induced pluripotent stem cells/iPSCs, or embryonic stem cells/ESCs) are the unique models used in cardiac development and heart regeneration research. We study heart cell differentiation, growth (maturation versus dedifferentiation), cell cycle (proliferation), cellular physiology, and how these processes are modulated by cellular cues such as bioengineered, nanopatterned surfaces. The overarching goals of our projects are to dissect molecular mechanisms regulating these multi-faceted processes in stem cells and heart cells and to generate important targets to enhance exogenous heart regeneration using cell therapies.
Integrative Functional Multi-Omics in Heart Diseases
The Zhang lab is interested in applying large-scale multi-omic approaches to discover and translate knowledge for treating cardiovascular diseases. By taking advantage of novel models for cell lineage tracking, cell cycle and epigenetic states visulization, and using both animal models and human biopsies, we study the integrative transcriptomic and epigenomic regulations (e.g., chromatin accessibility, histone and DNA modifications, and miRNAs) in cardiac development and disease remodeling. Our systematic investigations of global heart cell populations generate novel discoveries and comprehensive, in-depth knowledge that help develop new therapie to treat heart failure and other cardiac diseases.
Epigenetics of Diabetic Cardiocoplications
Dr. Zhang and his team also study epigenetic mechanisms of diabetic heart diseases by using state-of-the-art stem cell model systems and cellular electrophysiological platforms.
|1)||* Zhang Y C, Gago-Lopez N, Li N, Zhang Z, Alver N, Liu Y, Martinson AM, Mehri A, MacLellan WR C. Single-cell imaging and transcriptomic analyses of endogenous cardiomyocyte dedifferentiation and cycling. (Nature) Cell Discovery, 2019; 5: 30; June 4, 2019; PMCID: PMC6547664. DOI : 10.1038/s41421-019-0095-9|
|2)||* El-Nachef D, Oyama K, Wu YY, Liu Y, Zhang Y, MacLellan WR. Repressive histone methylation regulates cardiac myocyte cell cycle exit. J Mol Cell Cardiol. 2018; 121:1-12; PMID: 29800554 DOI: 10.1016/j.yjmcc.2018.05.013|
|3)||* Chen X*, Chakravarty T*, Zhang Y*, Li X, Zhong JF, Wang C. Single-cell transcriptome and epigenomic reprogramming of cardiomyocyte-derived cardiac progenitor cells. (Nature) Scientific Data. 2016; 3: 160079. PMID: 27622691 (*co-first author)|
|4)||* Zhang Y C, Zhong JF, Qiu H, MacLellan WR, Marban E, Wang C C. Epigenomic reprogramming of adult cardiomyocyte-derived cardiac progenitor cells. (Nature) Sci. Rep. 2015; 5: 17686; doi: 10.1038/ srep17686. PubMed PMID: 26657817 (‡Co-Corresponding author)|
|5)||* Zhang Y, Mignone J, MacLellan WR, Cardiac Regeneration and Stem Cells. Physiol. Rev. 2015; 95: 1189-204. PubMed PMID: 26269526|
|6)||Gago-Lopez N, Awaji O, Zhang Y, Ko C, Nsair A, Liem D, Stempien-Otero A, MacLellan WR. THY-1 receptor expression differentiates cardiosphere-derived cells with divergent cardiogenic differentiation potential. Stem Cell Report, 2014;2:1-16. PMID: 24936447|
|7)||* Zhang Y C, Matsushita N, Eigler T, Marban E C. Targeted microRNA interference promotes postnatal cardiac cell cycle re-entry. J Regenerative Med. 2013;2:2. PMID: 24910852|
|8)||* Malliaras K, Zhang Y, Seinfeld J, Galang G, Tseliou E, Cheng K, Sun B, Aminzadeh M, Marbán E. Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO Mol Med. 2013;5:191-209. PMID: 23255322|
|9)||Li Z, Zhang C, Weiner LP, Chiou PY, Zhang Y, Zhong JF. Molecular characterization of heterogeneous mesenchymal stem cells with single-cell transcriptomes. Biotechnol. Adv. 2013;31(2):312-7. PMID: 23266308|
|10)||Barth AS‡, Zhang Y‡, Li TS, Smith RR, Chimenti I, Terrovitis J, Davis D, Kizana E, Ho A, O’Rourke B, Wolff A, Gerstenblith G, Marban E. Functional impairment of human resident cardiac stem cells contributes to trastuzumab cardiotoxicity. Stem Cells Transl Med, 2012;1(4):289-97. PMID: 23197808 (‡ Co-first author)|
|11)||Li TS, Cheng K, Malliaras K, Matsushita N, Sun B, Marbán L, Zhang Y, Marbán E. Expansion of human cardiac stem cells in physiological oxygen improves cell production efficiency and potency for myocardial repair. Cardiovascular Res., 2011;89: 157-165. PMID: 20675298|
|12)||* Zhang Y, Li TS, Lee ST, Wawrowsky KA, Cheng K, Galang G, Malliaras K, Abraham RM, Wang C, Marban E. Dedifferentiation and proliferation of mammalian cardiomyocytes. PLoS One 2010; 5: e12559. PMID: 20838637|
|13)||Zhang Y, Xiao J, Wang H, Luo X, Wang J, Villeneuve LR, Zhang H, Bai Y, Yang B, Wang Z. Restoring depressed HERG K+ channel function as a mechanism for insulin treatment of the abnormal QT prolongation in diabetic rabbits. Am J Physiol Heart Circ Physiol. 2006;291:H1446-55. PMID: 16617123|
|14)||Zhang Y, Xiao J, Lin H, Luo X, Wang H, Bai Y, Wang J, Zhang H, Yang B, Wang Z. Ionic mechanisms underlying abnormal QT prolongation and the associated arrhythmias in diabetic rabbits: A role of rapid delayed rectifier K+ current. Cell Physiol Biochem 2007;19: 225-238. PMID: 17495463|
View a complete list of Publications in MyBibliography:
Our laboratory and institution provide a broad spectrum of learning opportunities for undergraduate students, graduate students and postdoctoral fellows in the following areas: Cellular Molecular Biology, Heart Diseases, Diabetes, Animal Models, Stem Cell Research and Regenerative Medicine, Genomics and Epigenetics, Electrophysiology, and Bioengineering.
The Zhang lab accepts graduate students who have already been admitted to the University of Hawaii Manoa (UHM) graduate programs. Candidates are encouraged to apply through the Department of Anatomy, Biochemistry and Physiology, or other departments at the UHM. For undergraduate students, independent study for potential credit and completion of an undergraduate thesis are highly encouraged. Outstanding and motivated undergraduates with necessary knowledge and skills from all departments who can commit at least 12 hours per week and plan to stay with our lab during the academic year, can contact Dr. Zhang by e-mail and submit a CV and statement of interest as a single PDF.
Research Scientist and Post-docs interested in the opportunities are encouraged to contact Dr. Zhang directly by sending the following documents in a single PDF file via e-mail: 1) a cover letter outlining their research interests and career plans; 2) CV; 3) Contact information of three references; 4) any selected publications.
Department of Anatomy, Biochemistry and Physiology https://abp.jabsom.hawaii.edu/faculty/
Institute for Biogenesis Research https://www.ibr.hawaii.edu/
Developmental and Reproductive Biology Graduation Program https://jabsom.hawaii.edu/grad_drb/