Ju Chen
University of California-San Diego, CA·Physiology
Heart muscle cells must build and maintain an internal scaffold, divide at the right stage of development, and insert proteins into the right membranes. When a single gene in these processes is mutated, people can develop cardiomyopathy, a disease of the heart muscle that leads to heart failure, dangerous rhythm disturbances and sudden death, often with no specific treatment available.
- Fields
Physiology
Genetics
Medicine & Clinical Research
- Topics
cardiomyopathy
filamin-C
p53
- Grants
- 4 known grants, through May 2030
What they work on
- Test whether mini-ALPK3, a shortened version of the ALPK3 kinase delivered by the muscle-targeting MyoAAV virus on the first day of life, prevents cardiomyopathy and early death in Alpk3 knockout mice.
- Determine whether mini-ALPK3 gene replacement given at one month reverses dilated cardiomyopathy, and at two months reverses the later thickened-wall (hypertrophic) stage, in Alpk3 knockout mice.
- Ask whether full-length filamin-C, reconstituted inside heart cells from three AAV vectors using self-joining split-intein segments, rescues heart function in both heart-specific Flnc knockout and Flnc heterozygous mice.
- Evaluate whether miniFLNC, a 5.7-kilobase filamin-C delivered as two AAV fragments joined by split-intein or StitchR, restores cardiac function in FLNC-deficient mice.
- Define ASNA1's role in heart formation and adult heart function using constitutive and tamoxifen-inducible heart-specific Asna1 knockout mice, including effects on the SGTA/BAG6/UBL4A pre-targeting complex.
- Determine how the ASNA1 V163A mutation causes loss of function, using knock-in mice and human iPSC-derived heart muscle cells carrying V163A or the patient's compound V163A/null genotype.
- Map how ATF4 regulates cardiomyocyte proliferation through p53-dependent and p53-independent target genes, using RNA sequencing and ATF4 binding-site mapping in embryonic ventricles of Atf4 knockout mice.
- Pinpoint the developmental window from embryonic day 7.5 to postnatal day 30 in which ATF4 is required for heart muscle cell proliferation, using tamoxifen-inducible heart-specific Atf4 deletion.
More about the research
The common strategy across these projects is to delete a gene only in heart muscle cells of mice—either from the beginning or switched off later in adulthood—to see what the protein normally does, then, where a therapy is plausible, to replace the missing gene using engineered viruses that home to muscle.
Why it matters
Inherited cardiomyopathies caused by FLNC, ALPK3 and ASNA1 mutations currently have no treatment that addresses the underlying protein deficit, and patients face heart failure, life-threatening arrhythmias and sudden death. Shortened genes delivered by muscle-targeting viruses could offer mutation-independent replacement therapy regardless of which mutation a patient carries. Mapping when ATF4 and p53 are needed in the developing heart could define a safer window for using ATF4 or p53 inhibitors in heart disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Joseph Powers
University of Washington, WA·Biophysics·Early-career
Test whether loss of Filamin C (FLNC), a protein linking the heart cell's contractile units to its surroundings, disrupts inside-out force transmission by altering filament lattice geometry in mouse cardiomyocytes, using X-ray diffraction, atomic force microscopy and multiscale modeling.
D Foster
Johns Hopkins University, MD·Physiology
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.
Michael Kapiloff
Stanford University, CA·Physiology
Define how phospholamban bound to AKAP6β at the outer nuclear membrane regulates calcium efflux from a nanometer-scale perinuclear compartment and myocyte growth, using live-cell imaging and biochemical assays in rat ventricular myocytes and human stem cell-derived cardiomyocytes.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.