About

Jidong Fu, PhD, is an Associate Professor in the Department of Physiology and Cell Biology at Ohio State College of Medicine. His laboratory focuses on understanding the fundamental mechanisms of cardiac cell fate control and cardiac electrophysiology during heart development, with the aim of developing new therapeutic approaches for cardiac regenerative medicine and anti-arrhythmic therapies. Dr. Fu has over 18 years of experience utilizing mouse and human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to study the development of cardiac electrophysiology and automaticity during the differentiation of ESC/iPSC-cardiomyocytes. His research investigates the role of IK1 in cardiac automaticity and anti-arrhythmic therapies, as well as strategies to facilitate the electrophysiological and functional maturation of ESC/iPSC-derived cardiomyocytes to improve their clinical application for cardiac regeneration. Additionally, Dr. Fu's work includes developing epigenetic approaches to directly convert cardiac fibroblasts into induced cardiomyocyte-like cells and exploring the biophysical modulation of microRNAs, revealing novel functions beyond their classical roles that could impact multiple cardiac proteins and diseases.

Research topics

• Biochemistry
• Biophysics
• Chemistry
• Cell biology
• Biology

Selected publications

• Abstract 4369500: MicroRNA-1’s Biophysical Function is essential for Postnatal Cardiac Maturation

  Circulation · 2025-11-03

  articleSenior author

  Background: MicroRNA-1 (miR1) plays a critical role in maintaining cardiac homeostasis. Full knockout of miR1 results in postnatal lethality. While prior studies have primarily focused on the canonical RNAi mechanism, we recently discovered a novel biophysical function of miR1, whereby it modulates the activity of its-bound proteins. Notably, a human single nucleotide polymorphism 14A/G of miR1 selectively disrupts the biophysical action without affecting its RNAi, indicating their mechanistic independence. Objective: To investigate the specific physiological significance of miR1’s biophysical function in cardiac development and function. Methods: Using CRISPR/Cas9 genome editing, we introduced a 14A/G point mutation into both miR1 gene loci and successfully generated homozygous transgenic mice (14G-Homo, miR1-1 14G/G ; miR1-2 14G/G ). Cardiac function was assessed longitudinally by echocardiography from postnatal-day 0.5 (P0.5) to 8 weeks. Neonatal cardiomyocytes (CMs, P1.5) were isolated for functional analyses. Results: Wild-type (WT) mice demonstrated normal postnatal cardiac growth, with left ventricle (LV) ejection fraction (EF) remaining stable at ~70% during the first postnatal week, followed by a decline to ~ 60% by P11.5. Stroke volume (SV) increased progressively, with a notable acceleration beginning at P11.5. In contrast, 14G-Homo mice exhibited significantly reduced EF as early as P0.5 (52±1.96% vs. WT 71±2.20%, p = 2.2×10 -5 ), despite a transient normalization by P3.5 (67±2.08% vs. WT 71±1.72%, p = 0.15). The accelerated increase in SV was markedly delayed in 14G-Homo mice until P14.5, resulting in significantly decreased SV (4.44±0.644��l vs. WT 10.68±0.401µl, p =1.6×10 -7 ). Pulse wave Doppler analysis showed that the E/A ratio reversal (≥1), a hallmark of enhanced LV diastolic function, occurred at P4.5 in WT mice. This reversal was delayed until P8.5 in 14G-Homo mice, indicating a delay in cardiac functional maturation. In vitro, WT neonatal CMs showed significant hypertrophic response to phenylephrine (PE), whereas both 14G-Homo CMs and WT CMs transfected with mutated 14G-miR did not. Importantly, reintroduction of WT miR1 restored PE-induced hypertrophy in 14G-Homo CMs. Conclusion: The biophysical function of miR1 is essential for timely postnatal cardiac maturation. These findings reveal a previously unrecognized mechanism of miRs and suggest that targeting its biophysical interactions may provide new therapeutic strategies for heart disease.

  PublisherDOI

• BPS2025 - MicroRNA-1 regulates glucose metabolism via biophysical modulation of ATP-sensitive potassium channel

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Advanced 4-chamber echocardiography techniques enable clinically matched precise characterization of heart disease progression in mice

  Communications Medicine · 2025-07-31 · 2 citations

  articleOpen accessSenior author

  Transthoracic echocardiography remains the primary non-invasive method for assessing cardiac function in clinical practice. However, technical challenges in acquiring accurate apical 4-chamber-long-axis (A4CLAX) views have historically limited mouse studies to left ventricle (LV) assessment using parasternal short-axis (SAX) M-mode imaging. To overcome this limitation, we developed an A4CLAX imaging approach for mice and performed a comparative analysis with established echocardiographic methods to assess cardiac function in healthy mouse hearts. To evaluate the utility of A4CLAX in detecting disease progression, we longitudinally monitored cardiac function of C57BL/6 N mice (male and female) following severe transverse aortic constriction (TAC), using both long-axis biplane (LAX-BP) and conventional SAX M-mode assays. Here we show that LAX-BP echocardiography demonstrates volumetric accuracy comparable to cardiac magnetic resonance (CMR) and detects significant LV functional decline within the first week post-TAC–changes that are not clearly captured by M-mode imaging. Importantly, A4CLAX further enables clinically relevant Doppler assessments, allowing detection of mitral valve regurgitation, restrictive filling patterns, and desynchronized valve motion. It also facilitates right ventricle (RV) functional evaluation and improved atrial visualization, revealing progressive enlargement of the left atrial (LA) and left atrial appendage (LAA) associated with worsening diastolic function. The A4CLAX imaging approach provides clinically comparable, comprehensive echocardiographic evaluation in murine models and offers improved sensitivity for detecting subtle changes in cardiac performance during disease progression. Echocardiography is a non-invasive imaging method commonly used to check heart function in people. However, it has been hard to get clear echocardiographic images of all heart chambers in mice. We imaged mouse hearts from a different direction in healthy mice and in a disease model that mimics heart pressure overload. Our method provided more accurate and detailed information than traditional techniques. It also allowed us to detect heart problems early, including valve issues and changes in heart chamber size and function. Our imaging method could be used to study heart disease and test treatments in mice, ultimately improving treatments for people. Kacira et al. develop an apical 4-chamber-long-axis (A4CLAX) echocardiographic imaging approach for mice. They demonstrate that the A4CLAX method provides clinically comparable and comprehensive evaluation of cardiac function in murine models, with the sensitivity to detect subtle changes in cardiac performance during disease progression.

  PublisherOA PDFDOI

• Abstract 4370781: Membrane-Repairing LncRNA Masir Protects the Heart from Ischemic Injury

  Circulation · 2025-11-03

  articleSenior author

  Background: Cardiomyocytes (CMs) undergo constant mechanical stress during contraction and are vulnerable to membrane damage. Impaired sarcolemmal integrity is a key factor of heart failure progression; hence, strengthening membrane repair represents a promising strategy for cardioprotection. While long non-coding RNAs (lncRNAs) are pivotal in cardiac function and disease, their direct involvement in membrane repair remains largely unexplored. Objective: To identify lncRNAs involved in membrane repair and evaluate their therapeutic potential in ischemic cardiac injury. Methods: Subcellular RNA fractionation (cytosolic, organellar, and plasma membrane) were isolated from heart tissues and sequenced to identify lncRNAs enriched at the plasma membrane (PM). Top candidate lncRNAs were assessed for their role in endocytosis, exocytosis and membrane repair using HL-1 cardiac muscle cells, neonatal CMs, and human induced pluripotent stem cell (iPSC)-differentiated CMs. Intramuscular delivery of lncRNAs was used to evaluate their therapeutic effect in a mouse model of myocardial infarction (MI). Results: Of the top 30 candidate lncRNAs, five PM-enriched lncRNAs were successfully cloned, synthesized, and purified, including Masir (MG53-associated sarcolemma injury repair lncRNA). Gfp RNA served as a control. Masir enhanced both endocytosis and exocytosis in HL-1 cardiac muscle cells. Importantly, rapid extracellular treatment of Masir significantly reduced laser-induced membrane injuries in HL-1 cells and wild-type neonatal CMs but had no effect in MG53-knockout CMs. In vivo, Masir -treated mice demonstrated improved cardiac function post-MI compared to Gfp -treated controls, with higher ejection fraction (34.29% ± 5.36, n=13 vs. Gfp : 21.53% ± 2.64, p =0.047) and significantly smaller scar size. Notably, mouse Masir RNA also attenuated laser-induced membrane injury in hiPSC-derived CMs, highlighting its translational relevance. Conclusion: Masir interacts with MG53, promotes sarcolemmal membrane repair, and confers protection against ischemic injury. These finding demonstrate a direct, functional role for lncRNAs in membrane repair and establish a foundation for RNA-based therapies targeting heart disease.

  PublisherDOI

• Long-Axis Biplane Echocardiography Sensitively Detects the Progressing Functional Deterioration of Mouse Heart

  Circulation Heart Failure · 2023-12-06 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• PO-01-123 THE BIOPHYSICAL ACTION OF MICRORNA IS ESSENTIAL TO MAINTAIN THE NORMAL FUNCTION AND ELECTROPHYSIOLOGY OF THE HEART

  Heart Rhythm · 2023-05-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Abstract 17637: Lacking MicroRNA-1’s Biophysical Action Causes Heart Failure Revealed by a Newly Developed Biplane Echocardiography of Mouse Heart

  Circulation · 2023-11-07

  articleSenior author

  MicroRNA-1 (miR1) is the most abundant microRNA in the heart and plays a key role in maintaining cardiac homeostasis through a well-known RNAi mechanism. Recently, we found a novel biophysical function of miR1 to physically bind to and modulate cardiac ion channels. A human single nucleotide polymorphism-hSNP14A/G (rs776480338) of miR1, in which the 14th nucleotide “A” is mutated to “G”, specifically abolishes the biophysical modulation while maintaining the RNAi. However, the physiological significance of microRNA’s biophysical action remains unknown. To study this, we created a single-nucleotide 14A/G mutation on miR1-1 and miR1-2 genes by using CRISPR/Cas9 and developed 14G-mutated homozygous (14G-Homo, miR1-1 14G/G:miR1-2 14G/G) transgenic mice. In addition, we also developed a new echocardiography methodology that can consistently record clear 4-chamber views of mouse hearts, allowing integration of 4-chamber and long axis views for the clinically recommended Biplane Simpson’s assessment of left ventricular (LV) function. Validation via Cardiac Magnetic Resonance (CMR) revealed that the Biplane method is more accurate than M-mode analysis for precise assessments of mouse LV functional parameters. These findings were highlighted in practice by monitoring both Wild Type (WT) and 14G-Homo mice at 2, 3, and 4 months of age, in which M-mode consistently overestimated LV parameters. Moreover, the clarity of the 4 chamber images enables many cardiac analyses that were previously not feasible for the mouse heart, such as the mitral valve color doppler that revealed turbulent blood flow into the LV of 14G-Homo mice. With the 4-chamber view methodology, we also studied the right ventricular (RV) function by assessing fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) and found that cardiac functional deterioration of 14G-Homo mice most likely originated in the LV, followed by RV deteriorations and development of heart failure. In conclusion, our study demonstrated that the biophysical action of miR1 is essential to cardiac homeostasis. Additionally, our new imaging methodology enables more clinically comparable analyses which significantly improve translational implications of mouse cardiac research.

  PublisherDOI

• The biophysical modulation and RNA interference are two independent actions of microRNA

  Biophysical Journal · 2023-02-01

  articleSenior author
  PublisherDOI

• Heart Rhythm Society Membership Committee Viewpoint: Update and current initiatives

  Heart Rhythm · 2023-04-27 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• MicroRNA-1 Deficiency Is a Primary Etiological Factor Disrupting Cardiac Contractility and Electrophysiological Homeostasis

  Circulation Arrhythmia and Electrophysiology · 2023-12-21 · 19 citations

  articleOpen accessSenior author

  BACKGROUND: MicroRNA-1 (miR1), encoded by the genes miR1-1 and miR1-2 , is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of miR1 has been associated with various heart diseases, where a significant reduction (>75%) in miR1 expression has been observed in patient hearts with atrial fibrillation or acute myocardial infarction. However, it remains uncertain whether miR1-deficiency acts as a primary etiological factor of cardiac remodeling. METHODS: miR1-1 or miR1-2 knockout mice were crossbred to produce 75%-miR1-knockdown (75%KD; miR1-1 +/− :miR1-2 −/− or miR1-1 −/− :miR1-2 +/− ) mice. Cardiac pathology of 75%KD cardiomyocytes/hearts was investigated by ECG, patch clamping, optical mapping, transcriptomic, and proteomic assays. RESULTS: In adult 75%KD hearts, the overall miR1 expression was reduced to ≈25% of the normal wild-type level. These adult 75%KD hearts displayed decreased ejection fraction and fractional shortening, prolonged QRS and QT intervals, and high susceptibility to arrhythmias. Adult 75%KD cardiomyocytes exhibited prolonged action potentials with impaired repolarization and excitation-contraction coupling. Comparatively, 75%KD cardiomyocytes showcased reduced Na + current and transient outward potassium current, coupled with elevated L-type Ca 2+ current, as opposed to wild-type cells. RNA sequencing and proteomics assays indicated negative regulation of cardiac muscle contraction and ion channel activities, along with a positive enrichment of smooth muscle contraction genes in 75%KD cardiomyocytes/hearts. miR1 deficiency led to dysregulation of a wide gene network, with miR1’s RNA interference–direct targets influencing many indirectly regulated genes. Furthermore, after 6 weeks of bi-weekly intravenous tail-vein injection of miR1 mimics, the ejection fraction and fractional shortening of 75%KD hearts showed significant improvement but remained susceptible to arrhythmias. CONCLUSIONS: miR1 deficiency acts as a primary etiological factor in inducing cardiac remodeling via disrupting heart regulatory homeostasis. Achieving stable and appropriate microRNA expression levels in the heart is critical for effective microRNA-based therapy in cardiovascular diseases.

  PublisherOA PDFDOI

Recent grants

• Biophysical Modulation of Cardiac Ion Channels by MicroRNA

  NIH · $4.5M · 2017–2027

Frequent coauthors

• Emre Bektik

  Brigham and Women's Hospital

  56 shared

• Ronald A. Li

  47 shared

• Adrienne T. Dennis

  43 shared

• Isabelle Deschênes

  The Ohio State University

  35 shared

• Kenneth R. Laurita

  MetroHealth

  34 shared

• Deepak Srivastava

  Harcourt Butler Technical University

  31 shared

• Deborah K. Lieu

  29 shared

• Chi‐Wing Kong

  University of Hong Kong

  29 shared

Education

• PhD

  Shanghai Institutes for Biological Sciences

  2006