Michael Kapiloff
Stanford University, CA·Physiology
Calcium ions act as a universal message inside cells, but the same ion can mean different things depending on exactly where in the cell it appears. Two projects here exploit that idea in two organs.
- Fields
Physiology
Neuroscience
Pharmacology
- Topics
calcium signaling
AKAP6β
mAKAPβ
- Grants
- 2 known grants, through Feb 2029
What they work on
- 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.
- Test whether disrupted calcium efflux from the AKAP6β compartment contributes to dilated cardiomyopathy, using adeno-associated virus vectors to add or remove perinuclear phospholamban function in normal and diseased mice.
- Study transcriptional and contractile defects in PLN R14del cardiomyopathy using patient-derived cardiomyocyte monolayers and engineered heart tissues, and test whether altering AKAP6β signaling is beneficial.
- Test whether endogenous CaMKII and CaMKIV are required for retinal ganglion cell survival after optic nerve crush, using knockout mice, AAV-delivered CaMKII-activating peptides, and transpupillary imaging of a CaMKII fluorescent reporter.
- Determine whether activated CaMKII targeted to specific intracellular compartments can promote neuron survival without suppressing optic nerve axon regeneration, and whether localized inhibitory peptides rescue regrowth.
- Identify the gene programs behind CaMKII-dependent neuroprotection using single-cell RNA and ATAC sequencing, and test retinal ganglion cell-specific Creb1 and Rela knockout mice for survival and axon regeneration.
More about the research
In the heart, the question is how calcium signals near the nucleus switch on the gene programs that make a failing heart remodel itself. In the eye, the question is how a calcium-activated enzyme can keep injured nerve cells alive without blocking their ability to regrow. Both projects use mouse models, virus-delivered genetic tools and imaging to separate helpful from harmful branches of the same signaling pathway.
Why it matters
Heart failure affects more than six million people in the United States, with roughly a million new diagnoses each year; understanding the calcium compartments that drive cardiac remodeling could point to targeted treatments, including for dilated cardiomyopathy caused by the PLN R14del mutation. Separately, optic nerve damage and retinal ganglion cell loss occur in glaucoma and ischemic optic neuropathies, and no therapy currently promotes these neurons' survival or axon regrowth; defining how CaMKII acts may inform treatments that protect vision.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Matthew Veldman
Medical College of Wisconsin, WI·Neuroscience
Determine when srebf2, a master regulator of cholesterol production, is needed in zebrafish retinal ganglion cells for optic nerve regeneration, using srebf2 activity reporter lines.
Karsten Gronert
University of California-Berkeley, CA·Neuroscience
Define which retinal cells make and respond to prostaglandin D2 (PGD2), a fat-derived signaling molecule, in healthy retina and how raised eye pressure (ocular hypertension) shuts this pathway down.
Ju Chen
University of California-San Diego, CA·Physiology
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.
The school
Stanford University: 87 labs on PI Pages, $1.6B a year on research, 739 research doctorates a year.
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