Modelling arrhythmogenic cardiomyopathy fatty-fibro pathology with PKP2-deficient epicardial cells derived from human iPSCs
Communications Biology
We use patient-derived iPSC-cardiomyocytes, single-cell genomics, and computational approaches to understand cardiac disease mechanisms and identify therapeutic targets.
Inherited heart diseases affect millions worldwide, yet most have no cure. The Churko Lab exists to change that. We create living models of cardiac disease using patient-derived stem cells, allowing us to study each person's unique disease in a dish and test potential treatments before they ever reach clinical trials.
Traditional approaches to understanding heart disease rely on animal models that often fail to predict human outcomes. We take a different approach: by reprogramming a patient's own cells into beating heart cells, we can recreate their exact genetic condition in the laboratory. This precision medicine approach reveals disease mechanisms that were previously invisible and accelerates the path from discovery to therapy.
Our work integrates cutting-edge technologies because the complexity of cardiac disease demands it. Single-cell genomics lets us see how individual cells malfunction. Machine learning helps us find patterns across thousands of genes. Multi-omics integration connects the dots from DNA to proteins to function. Together, these tools give us unprecedented insight into why hearts fail and how we might prevent it.
Dr. Jared Churko is an Associate Professor in the Department of Cellular and Molecular Medicine at the University of Arizona. Following postdoctoral training at the Stanford Cardiovascular Institute, he established an independent research program integrating human induced pluripotent stem cell technology with single-cell genomics and computational biology. His laboratory develops patient-derived iPSC models of inherited cardiac diseases, including arrhythmogenic cardiomyopathy, dilated cardiomyopathy, and atrial fibrillation, to identify disease mechanisms and therapeutic targets. He serves on the editorial boards of JMCC Plus and Circulation: Heart Failure, and reviews for multiple NIH study sections.
ACM is characterized by fibrofatty replacement of the myocardium, ventricular arrhythmias, and sudden cardiac death. We model desmosomal mutations (PKP2, DSP, DSG2) in iPSC-cardiomyocytes to understand how disrupted cell-cell junctions lead to electrical instability and progressive myocardial degeneration.
Bicuspid aortic valve affects 1-2% of the population and leads to progressive valve dysfunction and aortopathy. Using patient-derived iPSCs, we generate valvular interstitial cells and endothelial cells to model calcification, fibrosis, and the molecular mechanisms driving valve degeneration.
Mutations in sarcomeric proteins cause hypertrophic and dilated cardiomyopathy. We use high-throughput screening in iPSC-cardiomyocytes to identify small molecules that modulate myosin function, calcium sensitivity, and contractile dynamics— advancing precision therapeutics for inherited cardiomyopathies.
We are developing next-generation iPSC differentiation protocols that produce more mature, functional cardiac cells—cardiomyocytes, fibroblasts, endothelial, and epicardial cells—that better recapitulate human disease phenotypes. Using single-cell transcriptomics to benchmark against native tissue, we optimize these protocols to be faster, more cost-effective, and scalable for disease modeling and therapeutic screening.
We analyze patient-derived iPSC-cardiomyocytes using integrated multi-omics: whole-genome sequencing to identify variants, RNA-seq to measure transcriptional changes, and mass spectrometry to quantify protein alterations. This systems biology approach reveals disease mechanisms and therapeutic targets.
From single-cell resolution to whole-genome analysis, our platforms generate deep biological insights.
Bulk and single-cell RNA sequencing to profile gene expression, resolve cellular heterogeneity, and identify disease signatures and developmental trajectories.
Quantitative proteomics to measure protein abundance, post-translational modifications, and protein-protein interactions.
We engineer 3D cardiac tissues incorporating cardiomyocytes, fibroblasts, endothelial cells, and epicardial cells. These multicellular constructs better recapitulate the structural and functional properties of human myocardium.
Protein structure prediction and molecular modeling to understand ion channel dysfunction, sarcomeric mutations, and drug-target interactions.
Functional validation of omics discoveries using iPSC-cardiomyocytes. Electrophysiology, calcium imaging, and contractility assays for mechanistic studies and cardiotoxicity screening.
Deep learning models for gene regulatory network inference, drug response prediction, and integration of multi-modal biological data.
Our work appears in leading journals including Nature, Cell Stem Cell, Nature Methods, and Science Translational Medicine. Research from the lab has been cited over 6,000 times.
Communications Biology
Current Protocols
Circulation: Genomic and Precision Medicine
NPJ Regenerative Medicine
Nature Cardiovascular Research
Physiological Reports
Stem Cell Research
European Journal of Human Genetics
Stem Cell Reports
Tissue Engineering Part B: Reviews
Journal of Molecular and Cellular Cardiology (Cover Article)
Cardiovascular Research
Nature
Nature Communications
Cell Stem Cell
Nature Biomedical Engineering
Science Translational Medicine
Nature Cell Biology
Cell Stem Cell
Cell Stem Cell
Nature Methods
Circulation Research
Science Translational Medicine
Science Translational Medicine
Circulation Research
Physiology
Experimental Dermatology
Journal of Investigative Dermatology
Human Mutation
Biochemical Journal
Journal of Cell Science
Cardiovascular Research
Our iPSC expertise extends beyond the heart. Through collaborative projects, we generate patient-derived neural cells to model neurodegenerative diseases, applying the same precision medicine approach to understand disease mechanisms and identify therapeutic targets.
Serving on the editorial boards of Circulation: Heart Failure and JMCC Plus. Ad hoc reviewer for leading journals including Cell, Cell Stem Cell, Circulation, Nature Communications, Stem Cell Reports, Molecular Therapy, and Circulation: Genomic and Precision Medicine.
NIH NHLBI Cardiovascular Differentiation and Development study section, AHA Career Development and Fellowship committees, and international funding agencies including NSERC (Canada), Medical Research Council (UK), Swiss National Science Foundation, and Knowledge Foundation (Sweden). Member of the VA Institutional Biosafety and Research & Development Committees in Tucson.
Director of the UA American Heart Association Summer Undergraduate Research Fellowship (SURF) Program. Mentored 50+ trainees from high school through postdoctoral levels, with alumni advancing to medical school, PhD programs, and faculty positions. Served on thesis committees across Physiology, BME, Genetics, and Pharmacology programs, and as external PhD examiner for international institutions.
Interested in collaboration, joining the lab, or learning more about our research?
Life Science North, Room 407
1501 N Campbell Ave
Tucson, AZ 85724
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