Elizabeth Jonas
Yale University, CT·Neuroscience
When blood flow to the brain is briefly interrupted, some neurons do not die right away — they die hours or days later. In rodents, temporarily closing both carotid arteries (two-vessel occlusion, 2VO) kills neurons in the hippocampal CA1 region, a brain area needed for memory, and produces long-lasting memory deficits much like those seen in people after ischemic brain injury.
- Fields
Neuroscience
Physiology
Medicine & Clinical Research
- Topics
mitochondria
mPTP
ATP synthase
- Grants
- 1 known grant, through Feb 2029
What they work on
- Test whether mice carrying a low-leak mutant ATP synthase c-subunit are protected from delayed hippocampal CA1 neuron death after transient global ischemia induced by two-vessel occlusion in aged animals.
- Determine whether reducing c-subunit leak channel activity prevents the long-lasting hippocampal memory deficits that follow transient global brain ischemia in rodents.
- Characterize how cyclophilin D binding at the OSCP subunit of the ATP synthase stator, and its blockade by cyclosporine A, controls opening of the ATP synthase c-subunit leak channel in neuronal mitochondria.
- Evaluate dexpramipexole, which binds OSCP/subunit b on the ATP synthase stator, as a modulator of mitochondrial leak in injured neurons.
More about the research
Understanding what tips these cells into delayed death is the central problem here, because the window between injury and death is a window for treatment.
Why it matters
Brain ischemia from events such as cardiac arrest or stroke is a major cause of death and disability in older adults, and survivors often live with lasting memory problems. By identifying the ATP synthase c-subunit as the pore that lets mitochondria leak during injury, and by showing that a channel-reducing mutation protects brain and heart tissue in mice, this work points to a specific molecular target. Drugs such as dexpramipexole that bind ATP synthase could eventually be tested as ways to limit delayed neuronal death.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Evgeny Pavlov
New York University, NY·Biochemistry
Identify which molecular mechanisms of mitochondrial permeability transition operate under specific stress conditions, such as calcium and reactive oxygen species imbalance, using the lab's animal and cell disease 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.
Pamela Wenzel
University of Texas Health Science Center at Houston, TX·Biology
Test how interrupting mitochondrial maturation affects commitment of hemogenic endothelium (blood-forming vessel cells) to blood fate, using drugs, in vitro vessel-mimicking platforms and cardiac mutant mice.
The school
Yale University: 73 labs on PI Pages, $1.5B a year on research, 438 research doctorates a year.
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