Luke Judge
University of California-San Francisco, CA·Genetics
Inherited diseases that destroy spinal motor neurons, the nerve cells that drive muscle movement, are among the most common disabling genetic disorders and have no effective treatment. Many are dominant, meaning one faulty copy of a gene causes disease even though the second copy is healthy.
- Fields
Genetics
Neuroscience
Medicine & Clinical Research
- Topics
Charcot-Marie-Tooth disease
neurofilament light chain
motor neuron disease
- Grants
- 1 known grant, through Jun 2027
What they work on
- 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.
- Experimentally identify the non-coding regulatory sequences that control expression of NEFL, the nerve filament gene mutated in CMT2E, since many common variants fall in these regions.
- Screen systematically for common heterozygous variants that sit alongside the disease mutation and can be targeted by editing to excise coding or critical regulatory regions and inactivate the mutant NEFL allele.
More about the research
Gene editing could in principle switch off only the faulty copy, but that demands extraordinary precision, because the two copies often differ by just a single DNA letter. A further obstacle is that one gene can harbor dozens of different disease-causing mutations, and designing a separate therapy for each is impractical. This project develops a gene editing strategy meant to cover many mutations at once, using Charcot-Marie-Tooth disease type 2E (CMT2E) as a test case.
Why it matters
Charcot-Marie-Tooth type 2E causes severe, disabling nerve degeneration with no treatment available. An editing approach that silences the disease copy of NEFL by targeting common nearby variants, rather than each rare mutation one at a time, could in principle serve a large share of patients with a single set of reagents, and the same strategy could extend to other dominant motor neuron diseases including other forms of CMT2 and ALS.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
X. Shawn Liu
Columbia University, NY·Neuroscience
Test whether reactivating the healthy MECP2 copy on the silenced X chromosome, by removing promoter methyl tags with dCas9-Tet1, rescues Rett syndrome symptoms in female mouse models.
Charlotte Sumner
Johns Hopkins University, MD·Neuroscience
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.
Jeffrey D Milbrandt
Washington University in St Louis, MO·Neuroscience
Determine how regulatory ubiquitin tags, including those added by Parkin after mitochondrial damage, change the activity of SARM1, the NAD+-destroying enzyme that executes axon degeneration.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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