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TingTing Hong

TingTing Hong, MD, PhD

Academic Information

Departments College of Pharmacy , Member - Diabetes & Metabolism Research Center , Investigator - Nora Eccles Harrison Cardiovascular Research & Training Institute , Associate Professor - Pharmacology & Toxicology

Academic Office Information

Research Interests

  • My laboratory focuses on understanding the regulation and remodeling of membrane microdomains of cardiomyocytes during heart failure progression


My laboratory focuses on understanding the regulation and remodeling of membrane microdomains of cardiomyocytes during heart failure progression. We study how cardiomyocyte surface microdomains are organized to concentrate ion channels and signaling proteins for proper function and regulation in normal and failing hearts. The research interested includes the mechanisms of scaffolding protein and cytoskeleton-based maintenance of membrane structures and subdomains important in calcium signaling, turnover mechanisms of microdomains, and the mechanisms of heart failure progression. The goal is to identify, at the bench, new molecular and cellular targets that can be translated to develop new therapeutic tools for clinical management of heart failure.

Targeting cBIN1-microdomains for heart failure therapy development

Transverse-tubules (T-tubules) are membrane invaginations specific to striated muscles. Cardiac T-tubules are enriched with L-type calcium channels (LTCCs), which form dyads with ryanodine receptors (RyRs) to initiate intracellular calcium signaling critical for the beat-to-beat heart contraction. We previously identified that a membrane curvature protein, the cardiac isoform of BIN1 (Bridging Integrator 1) now called cBIN1, folds the membrane bilayer within T-tubules to control extracellular ion diffusion, protecting the hearts from arrhythmias (Figure 1). Over the years, we have identified that cBIN1-microdomains regulate myocardial function by facilitating microtubule-dependent LTCC delivery, clustering LTCCs and recruiting RyRs for effective dyad formation, and organizing SERCA2a for effective diastolic calcium removal and myocardial relaxation. In heart failure, disruption of cBIN1 microdomains causes impaired myocardial function, which can be normalized by cBin1 gene therapy. We are now further resolving the fundamental cell biology underlying cBIN1-microdomain formation, regulation, and turnover. The translational goal is to explore new strategies, via targeting cBIN1-microdomains, to develop novel therapies effective for patients with heart failure.

Microdomain Turnover and cBIN1 Extracellular Vesicles

On the other hand, cardiomyocyte T-tubule cBIN1-microdomains turn over through microparticle release, and blood cBIN1 can aid in diagnosis and prognosis of heart failure. We also identified that cBIN1-microparticle release involves the ESCRT-III subunit CHMP4B (Figure 2), which is expressed in the mammalian cardiomyocytes and interacts with cBIN1.

For the first time, the BAR domain containing protein superfamily is found to serve as an early ESCRT factor to initiate the biogenesis of extracellular vesicles. These results introduce a new paradigm that cardiomyocyte membrane undergoes dynamic turnover, releasing membrane microdomains. We are currently further exploring the release mechanism, functional significance, and therapeutic potential of these cardiac origin cBIN1 vesicles.


FAR Webpage

College of Pharmacy

Education History

Graduate Training Beijing Medical University (Peking University Health Science Center)
Peking University
Doctoral Training University of Michigan
University of California
Postdoctoral Fellow

Selected Publications

Journal Article

  1. Li J, Richmond B, Cluntun AA, Bia R, Walsh MA, Shaw K, Symons JD, Franklin S, Rutter J, Funai K, Shaw RM, Hong T. Cardiac gene therapy treats diabetic cardiomyopathy and lowers blood glucose. JCI Insight. 2023 Sep 22;8(18). doi: 10.1172/jci.insight.166713. PubMed PMID: 37639557; PubMed Central PMCID: PMC10561727.

  2. Khan MS, Smego D, Ishidoya Y, Hirahara AM, Offei E, Ruiz Castillo MS, Gharbia O, Li H, Palatinus JA, Krueger L, Hong T, Hoareau GL, Ranjan R, Selzman CH, Shaw RM, Dosdall DJ. A canine model of chronic ischemic heart failure. Am J Physiol Heart Circ Physiol. 2023 Jun 1;324(6):H751-H761. doi: 10.1152/ajpheart.00647.2022. Epub 2023 Mar 24. PubMed PMID: 36961487; PubMed Central PMCID: PMC10151054.

  3. Palatinus JA, Valdez S, Taylor L, Whisenant C, Selzman CH, Drakos SG, Ranjan R, Hong T, Saffitz JE, Shaw RM. GJA1-20k Rescues Cx43 Localization and Arrhythmias in Arrhythmogenic Cardiomyopathy. Circ Res. 2023 Mar 17;132(6):744-746. doi: 10.1161/CIRCRESAHA.122.322294. Epub 2023 Feb 22. PubMed PMID: 36927183; PubMed Central PMCID: PMC10314823.

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