Erin Seifert
Thomas Jefferson University, PA·Physiology
Mitochondria are the compartments where cells burn fuel to make ATP, the molecule that powers almost everything a cell does. When mutations or toxins cripple that machinery, the result is primary mitochondrial disease, which affects roughly 1 in 5,000 people.
- Fields
Physiology
Biochemistry
Medicine & Clinical Research
- Topics
primary mitochondrial disease
mitochondrial myopathy
oxidative phosphorylation
- Grants
- 2 known grants, through Feb 2028
What they work on
- Determine the fate of fatty acid fuel in skeletal muscle lacking the mitochondrial phosphate carrier PiC and in intact liver and heart, using fatty acid tracers and measurement of beta-oxidation intermediates in tissues and serum.
- Test whether insulin-stimulated glucose uptake into oxphos-deficient muscle depends on greater fat storage and oxidation by liver and heart, using hyperinsulinemic-euglycemic clamps with radiolabeled glucose and a non-metabolizable glucose analog.
- Test whether lipid accumulation in oxphos-deficient muscle activates the integrated stress response and thereby drives production and secretion of FGF21, a hormone proposed to couple muscle to liver and heart.
- Test whether calcium entry through the mitochondrial calcium uniporter complex improves energetics early in mitochondrial dysfunction, by depleting the uniporter in PiC-deficient and frataxin-deficient mouse models.
- Determine how the uniporter complex contributes to endoplasmic reticulum stress and the integrated stress response, and the consequences for cell viability, protein translation and muscle mass.
- Test whether regulation of the uniporter by MICU3 makes mitochondria vulnerable to sustained opening of the permeability transition pore, a channel linked to cell death, at later stages of myopathy, using compartment-specific genetic sensors and imaging.
More about the research
Skeletal muscle is among the hardest-hit tissues, producing mitochondrial myopathy: muscle wasting, weakness and poor exercise capacity. Mouse studies indicate that the energy shortage itself is not the whole story. Instead, failing mitochondria set off a cascade of adaptive and maladaptive changes in metabolism and in protein quality control, and switch on stress programs including endoplasmic reticulum stress and the integrated stress response. Two projects in this lab ask how muscle, and the body as a whole, handle that situation: one follows the fate of fat as a fuel across organs, and the other asks how calcium entering mitochondria helps or harms diseased muscle.
Why it matters
People with primary mitochondrial disease often suffer progressive muscle weakness with no effective treatment, and the damage comes as much from the cell's stress responses as from the energy shortfall itself. Mapping how fat is redistributed among muscle, liver and heart, how FGF21 coordinates that shift, and when mitochondrial calcium entry helps versus harms could identify points of intervention to preserve muscle mass and exercise capacity, and could inform other myopathies and stress conditions where the same pathways switch on.
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.
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.
Rexford Ahima
Johns Hopkins University, MD·Physiology
Investigate how muscle IPMK, an energy-sensing enzyme, controls fuel use in living mice at rest and during exercise, using mice in which IPMK is deleted only in skeletal muscle.
The school
Thomas Jefferson University: 12 labs on PI Pages, $271M a year on research, 33 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.