Susan L Hamilton
Baylor College of Medicine, TX·Physiology
Muscle contraction depends on calcium, which is stored inside muscle cells in a compartment called the sarcoplasmic reticulum (SR). It is released on command through a channel protein called RYR1 (ryanodine receptor type 1).
- Fields
Physiology
Biochemistry
Genetics
- Topics
skeletal muscle
excitation-contraction coupling
calcium signaling
- Grants
- 2 known grants, through Mar 2031
What they work on
- Test whether the kinase SPEG phosphorylates the muscle calcium channel RYR1 at serine 2902 through its second kinase domain to limit sarcoplasmic reticulum calcium leak, and identify other targets of SPEG's kinase domains in skeletal muscle.
- Determine whether the phosphorylation-mimicking RYR1 S2902D mutation in mice slows age-related decline in muscle and mitochondrial function, improves function in myopathy models, and alters exercise-driven mitochondrial biogenesis.
- Assess whether the drug S107 improves muscle function in wild-type, S2902D, Y524S and SPEG-deficient mice, and use S2902D mice to uncover possible off-target effects.
- Define how heat, glycolysis, lactate and brown fat thermogenesis, together with RYR1 calcium leak and AMPK activation in muscle, raise heat sensitivity in mice susceptible to malignant hyperthermia.
- Determine whether epigenetic changes driven by heat exposure in muscle and brown adipose tissue are sex-biased and passed on to offspring, helping explain variable disease penetrance.
More about the research
When RYR1 leaks calcium at the wrong times, muscles weaken, produce excess heat and change their metabolism. Inherited mutations in RYR1 and related proteins cause congenital myopathies, muscle diseases present from birth. They also cause malignant hyperthermia susceptibility (MHS), a dangerous reaction to certain anesthetics, and raise the risk of environmental heat stroke (EHS). Both of the lab's projects study how SR calcium leak is controlled, and how it shapes muscle function and heat sensitivity in mice.
Why it matters
People with RYR1 mutations, including feverish children, athletes and military personnel in hot environments, can suffer life-threatening heat stroke or malignant hyperthermia. There are no effective treatments for episodes that happen outside clinical settings. This work could identify ways to prevent these heat-related deaths. It may also establish whether blocking calcium leak, for example with drugs like S107, is a useful treatment approach for congenital myopathies.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Shey-Shing Sheu
Thomas Jefferson University, PA·Physiology
Test whether hypertrophic stress raises levels of mitochondrial ryanodine receptor type 1 (mRyR1), a calcium channel, to boost mitochondrial calcium uptake and ATP production, using RyR1-overexpressing and other mouse models.
Min Du
Washington State University, WA·Physiology
Test whether maternal obesity suppresses AMPK, an energy-sensing enzyme, and thereby blocks embryonic progenitor cells from committing to a muscle fate, using single-cell omics analysis of mouse embryonic tissue.
Martin Morad
University of South Carolina-Columbia, SC·Physiology
Compare calcium-signaling defects caused by CPVT1 mutations in different regulatory regions of the cardiac calcium-release channel RyR2 in maturated human iPSC-derived heart cells, reverse them by editing the sequence back, and test drug responses.
The school
Baylor College of Medicine: 38 labs on PI Pages, $881M a year on research, 115 research doctorates a year.
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