Michael Bround
Baylor College of Medicine, TX·Physiology·Early-career
When blood flow returns to the heart after a heart attack, it causes a second wave of damage called reperfusion injury. In muscular dystrophy, muscle fibers die off step by step.
- Fields
Physiology
Medicine & Clinical Research
Biochemistry
- Topics
mitochondria
calcium overload
ischemia reperfusion injury
- Grants
- 2 known grants, through May 2031
What they work on
- 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.
- Test whether LETM1 is a therapeutic target after a heart attack by changing its activity through the regulatory phosphorylation site LETM1-pT191 in a mouse model of heart injury from blocked and then restored blood flow.
- Measure how much the sodium/calcium exchangers NCLX and TMEM65 each contribute to calcium release from heart mitochondria, and confirm the main findings in heart muscle cells derived from humans.
- Test whether mitochondrial calcium overload causes muscle fiber death in Mdx muscular dystrophy mice by deleting Nclx (calcium out), Mcu (calcium in) or Mcub (a brake on calcium uptake) in muscle fibers.
- Measure how much ANT proteins, part of the cell-killing permeability transition pore, contribute to muscular dystrophy by deleting Ant1, Ant2 or all ANT forms in Sgcd-/- mice and treating them with the cyclophilin D blocker Debio-025.
More about the research
In both diseases, mitochondria, the cell's energy-producing compartments, take up too much calcium, and this overload can trigger cell death. Both projects ask which proteins move calcium into and out of mitochondria in heart and skeletal muscle. They also ask whether adjusting those proteins can limit tissue damage.
Why it matters
Heart attack injury and muscular dystrophy currently have no therapy that prevents mitochondria-driven tissue death. By identifying which proteins remove calcium from mitochondria, and how much damage comes from the permeability pore, the work could point to new drug targets. Such drugs might reduce heart damage after a heart attack or slow muscle wasting in patients with muscular dystrophy. The grants also note possible relevance to Alzheimer's disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Ming-Feng Tsai
University of Virginia, VA·Biophysics
Establish how MICU3, a neuron-specific subunit of the mitochondrial calcium uniporter, boosts the channel's calcium uptake, using biochemical, electrophysiological and structural methods.
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.
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
Baylor College of Medicine: 38 labs on PI Pages, $881M a year on research, 115 research doctorates a year.
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