Bradford Hill
University of Louisville, KY·Physiology
After a heart attack, the heart repairs itself by forming scar tissue made largely of collagen, the main structural protein of connective tissue. Too much scarring, called fibrosis, stiffens the heart and worsens how it remodels after injury.
- Fields
Physiology
Biochemistry
Medicine & Clinical Research
- Topics
cardiac fibrosis
myocardial infarction
heart attack
- Grants
- 1 known grant, through Nov 2027
What they work on
- 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.
- Test whether a 'PEP-slow' cycle driven by Pkm2 speeds glycine synthesis and amplifies collagen secretion in fibroblasts isolated from infarcted hearts or treated with the scarring signal TGF-β.
- Define how the PEP cycle, including the enzyme Pck2 that adds carbon back into the loop, influences heart fibrosis after infarction, using Pck2 deletion in fibroblasts.
- Assess whether drugs that activate Pkm2, giving it Pkm1-like activity, reduce collagen abundance in isolated cardiac fibroblasts.
More about the research
No approved therapies currently reduce it. Fibroblasts, the cells that build this scar, produce collagen at enormous rates: a single cell can make more than 500,000 collagen protein chains per hour. Meeting that demand requires the cell to rewire its metabolism so that carbon flows into making glycine and proline, two amino acids that make up much of collagen.
Why it matters
Cardiac fibrosis after a heart attack has no approved treatment, and the processes that drive it are poorly understood. By showing how fibroblast metabolism fuels collagen production, this work could identify targets in the PEP cycle, such as the Pkm2 and Pck2 enzymes, for drugs that limit harmful scarring. Such drugs could eventually help patients recovering from myocardial infarction.
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.
Xiaolei Liu
Temple University, PA·Physiology
Determine the molecular pathways and targets through which lymphatic growth in the heart improves cardiomyocyte survival after myocardial infarction, building on survival signals such as Reelin released by lymphatic endothelial cells.
Conrad Hodgkinson
Duke University, NC·Biomedical Engineering
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.
The school
University of Louisville: 15 labs on PI Pages, $225M a year on research, 159 research doctorates a year.
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