Shey-Shing Sheu
Thomas Jefferson University, PA·Physiology
A beating heart needs a steady supply of energy, made inside cells by mitochondria in the form of ATP, the cell's energy currency. Heart failure has many causes, but faulty energy supply and oxidative stress appear central.
- Fields
Physiology
Medicine & Clinical Research
Pharmacology
- Topics
heart failure
cardiac hypertrophy
ryanodine receptor
- Grants
- 1 known grant, through Mar 2027
What they work on
- 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.
- Determine whether chronic mitochondrial calcium overload drives sustained reactive oxygen species (ROS) production through the Rieske iron-sulfur protein (RISP) at complex III of the mitochondrial energy chain.
- Test whether ROS make nearby RyR2 channels leak calcium from the sarcoplasmic reticulum, setting up a vicious cycle that opens the mitochondrial permeability transition pore and causes energy failure and heart muscle cell death.
More about the research
Oxidative stress is damage from reactive oxygen species (ROS), reactive molecules that can harm proteins. Calcium is thought to link each heartbeat to energy production. When calcium enters mitochondria, it speeds up the enzymes that make ATP. Researchers call this excitation-bioenergetics (EB) coupling. The best-known calcium entry route into mitochondria is the mitochondrial calcium uniporter (MCU). Yet hearts without MCU have only minor energy problems, which suggests that other calcium channels also help.
Why it matters
Cardiac hypertrophy and heart failure affect many patients, and energy failure in heart cells is a key driver. If RyR1 turns from helpful to harmful in stressed hearts, drugs that block RyR1 more than RyR2 could treat these conditions. One example is dantrolene, already used for malignant hyperthermia.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dmitry A Terentyev
Ohio State University, OH·Physiology
Test whether overactive RyR2, the heart's calcium-release channel, activates calpain, a calcium-activated enzyme inside mitochondria, which then breaks down OPA1, a protein that shapes mitochondrial inner folds, using a rat model of CPVT the lab created.
Michael Bround
Baylor College of Medicine, TX·Physiology·Early-career
Determine whether LETM1 drives proton/calcium exchange in heart mitochondria, using mice in which Letm1 is deleted from the heart to study heart function, mitochondrial function and how charged particles cross the mitochondrial membrane.
Lai-Hua Xie
Rutgers University-New Brunswick, NJ·Physiology
Determine whether the mitochondrial calcium uniporter (mCU), a channel admitting calcium into mitochondria, also carries iron into heart-cell mitochondria and drives calcium dysregulation, oxidative stress and iron-induced cardiac toxicity, in isolated myocytes and in vivo.
The school
Thomas Jefferson University: 12 labs on PI Pages, $271M a year on research, 33 research doctorates a year.
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