Charlotte Sumner
Johns Hopkins University, MD·Neuroscience
Spinal muscular atrophies (SMAs) are inherited diseases in which motor neurons, the nerve cells that control muscles, fail. The result is severe muscle weakness and often early death.
- Fields
Neuroscience
Genetics
Medicine & Clinical Research
- Topics
spinal muscular atrophy
distal SMA
motor neuron disease
- Grants
- 1 known grant, through Apr 2029
What they work on
- Dissect how levels of SMN protein, which declines sharply around birth in SMA, are regulated during development and during treatment with SMN-inducing drugs, using patient data, mice and iPSC-derived motor neurons.
- Identify the molecular mechanisms that cause SMA motor neurons to mature poorly before birth and degenerate rapidly after birth.
- Develop new SMA therapies, including treatments given in utero, based on the timing of disease onset before birth.
- Characterize protein-protein interactions that control the TRPV4 ion channel and test how mutant TRPV4 disrupts the barrier function of blood vessel endothelial cells.
- Assess TRPV4 antagonists, drugs that block the channel, as a therapy in distal SMA knock-in mice with blood-neural barrier breakdown.
More about the research
Each form is caused by a single gene. This program aims to improve treatments for two forms. Proximal SMA is caused by loss-of-function mutations in SMN1 (survival motor neuron 1). Distal SMA (dSMA) is caused by mutations in TRPV4, a channel on the cell surface that lets positive ions in. The approach combines findings from patients with experiments in mice and in motor neurons grown from induced pluripotent stem cells (iPSCs), which are adult cells reprogrammed into stem cells.
Why it matters
Current SMA gene therapies help some patients far more than others. Finding what limits them, and whether treating before birth helps, could improve outcomes for children with proximal SMA. TRPV4-blocking drugs, already well tolerated in people, could become a treatment for distal SMA. They may also help other disorders involving breakdown of blood-neural barriers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Adam Norris
University of California-Riverside, CA·Genetics
Determine how the broadly expressed RNA binding protein MEC-8/RBPMS produces cell-specific outcomes by identifying its physiologically relevant RNA targets in different C. elegans cell and tissue types.
Luke Judge
University of California-San Francisco, CA·Genetics
Test allele-specific genome editing against two different dominant CMT2E mutations and develop rigorous phenotypic assays of therapeutic benefit in motor neurons derived from patient-modeled human induced pluripotent stem cells.
Heather L Montie
Philadelphia College of Osteopathic Medicine, PA·Neuroscience
Test whether excess CD38 activity, which breaks down the energy molecule NAD+, drives NAD+ depletion and motor decline in AR100Q and AR113Q knock-in mouse models of SBMA.
The school
Johns Hopkins University: 100 labs on PI Pages, $4.1B a year on research, 622 research doctorates a year.
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