D Foster
Johns Hopkins University, MD·Physiology
Vitamin A does more than support vision. The body converts it into all-trans retinoic acid (ATRA), a hormone that switches many genes on and off, including genes important for heart function.
- Fields
Physiology
Medicine & Clinical Research
Biochemistry
- Topics
heart failure
all-trans retinoic acid
vitamin A
- Grants
- 1 known grant, through Mar 2027
What they work on
- Identify the enzymes that convert vitamin A to retinoic acid in adult heart muscle cells, starting from DHRS4, using heart muscle cells and engineered heart tissue grown from human stem cells.
- Test whether low ATRA causes poor heart relaxation and whether raising ATRA can prevent or reverse heart failure, using CRBP1-knockout mice and mice lacking DHRS4 only in the heart.
- Identify genes that respond to ATRA by adjusting DHRS4 and ATRA levels in mouse hearts and in engineered human heart tissue.
- Measure retinoids and retinoid-related proteins across heart failure types (HFrEF, HFpEF, ischemic and hypertrophic cardiomyopathy) using targeted mass spectrometry and MALDI imaging.
More about the research
The team has found that ATRA levels in the heart drop by up to 40% in a common type of heart failure called idiopathic dilated cardiomyopathy, and in an animal model, even when vitamin A intake is adequate. Giving ATRA prevented heart failure in mice whose hearts were under strain from high pressure. But ATRA affects many tissues and breaks down quickly in the blood. Targeting the heart enzymes that make ATRA may therefore be a more precise way to treat heart failure.
Why it matters
Heart failure has many forms, and better targeted treatments are needed. If low heart ATRA drives some types, the enzymes that make ATRA could become drug targets that restore normal levels without the side effects of giving ATRA to the whole body. Measuring ATRA across heart failure types may show which patients could benefit from such a therapy.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Tammy Kindel
Medical College of Wisconsin, WI·Medicine & Clinical Research
Test whether the gut microbiome after sleeve gastrectomy raises blood bile acids that activate FXR, a bile-acid sensor, using fecal transfer from operated mice and metagenomic sequencing of rodent and human stool.
Igor Shmarakov
Rutgers University-New Brunswick, NJ·Biochemistry
Determine how endothelial cells, lipofibroblasts and type 2 alveolar epithelial cells take up retinoids from circulating lipoproteins and share them with one another. The approach uses tracer-labeled retinoids, mice lacking Lpl, Cd36 or Lrp1 in specific cells, cultured cells and lipidomics.
Xuebing Wu
Columbia University, NY·Genetics
Test whether RPL3L ribosomes, which replace the common ribosomal protein RPL3 in muscle, promote protein homeostasis in heart muscle cells, using human cell lines and mice expressing mainly RPL3 or RPL3L.
The school
Johns Hopkins University: 100 labs on PI Pages, $4.1B a year on research, 622 research doctorates a year.
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