Conrad Hodgkinson
Duke University, NC·Biomedical Engineering
After a heart attack, dead muscle is replaced by scar made largely of fibroblasts, and the heart never regains full pumping strength. One repair strategy is to convert those scar fibroblasts directly into new heart muscle cells inside the living heart.
- Fields
Biomedical Engineering
Genetics
Medicine & Clinical Research
- Topics
cardiac reprogramming
direct reprogramming
cardiac fibroblasts
- Grants
- 1 known grant, through Feb 2029
What they work on
- Test whether the Cbx1-PurB-Sp3 repressor complex silences cardiomyocyte genes by forcing a DNA loop that blocks enhancer access, using binding-site deletions, repositioning and variable helical twists in a luciferase promoter-reporter construct.
- Determine whether knocking down a single member of the Cbx1-PurB-Sp3 complex reproduces the gene de-repression seen with combined knockdown, given the apparent cooperativity among the three proteins.
- Test in fibroblast lineage-tracing mice whether fibroblast-selective C166-derived exosomes carrying miR combo plus a repressor-targeting siRNA improve reprogramming, infarct size and function by echocardiography, given immediately or up to four weeks after infarction.
- Measure uptake of C166-derived exosomes loaded with fluorescently labeled miRNAs by fibroblasts, cardiomyocytes and endothelial cells in infarcted Yorkshire mini-pigs, and test functional benefit of the combined therapy.
More about the research
This works, but the functional gains have been modest. Three obstacles are proposed as the reason: the reprogramming cargo is given at the wrong time, molecular brakes inside fibroblasts hold heart-muscle genes shut, and the cargo does not reach fibroblasts efficiently. This project attacks all three.
Why it matters
Heart attack survivors are left with scar tissue that weakens the heart and leads to heart failure. Turning that scar back into working muscle, with better targeting and the molecular brakes released, could improve pump function after infarction. The large-animal pig studies are a step toward testing such a therapy in patients, and the work also defines transcriptional repressors as a previously unrecognized barrier to cell reprogramming generally.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Shah Ali
Columbia University, NY·Medicine & Clinical Research
Build a genetic mouse model in which the biotin-tagging enzyme TurboID sits in the endoplasmic reticulum of cardiac fibroblasts, so the proteins these scar-forming cells secrete can be labeled in living animals.
Malcolm Maden
University of Florida, FL·Biology
Determine whether the spiny mouse heart truly regenerates after a heart attack through cardiomyocyte division, using tissue staining for fibrosis, cell division and cell death, compared with lab mice.
Bradford Hill
University of Louisville, KY·Physiology
Determine how alternative splicing of Pkm, which switches fibroblasts between the slower Pkm2 and faster Pkm1 enzyme forms, changes cardiac fibroblast metabolism and the amount of fibrosis after myocardial infarction.
The school
Duke University: 61 labs on PI Pages, $1.6B a year on research, 417 research doctorates a year.
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