Eric M Morrow
Brown University, RI·Neuroscience
Single genetic changes can derail how a brain is built or cause particular neurons to die decades later. Work in this lab follows several such genetic conditions from the clinic back to the laboratory bench, using patient families, mouse and rat models, and neurons grown from patient stem cells.
- Fields
Neuroscience
Genetics
Biochemistry
- Topics
autism
neurodevelopmental disorders
copy number variant
- Grants
- 4 known grants, through Jun 2029
What they work on
- Map gene-expression and molecular pathway changes in embryonic brain of 17q12-deletion mice, testing whether reduced dosage of genes in the interval, including the Wnt-regulating transcription factor Lhx1, disrupts early brain development.
- Test Wnt-related small molecules for rescue of molecular defects in neurons derived from induced pluripotent stem cells of patients with 17q12 deletions and reciprocal duplications.
- Characterize postnatal brain structure and behavior of 17q12-deletion mice on inbred C57BL/6N versus outbred CD-1 backgrounds using MRI morphometry, to ask how genetic background drives severity.
- Define transcriptomic and metabolomic signatures of vulnerable locus coeruleus neurons before and during cell death in Gpt2-null mice and in Alzheimer's disease and Down syndrome mouse models.
- Determine which cells need the mitochondrial enzyme Gpt2 by deleting it selectively in locus coeruleus noradrenergic neurons or in glia, and test whether extended wakefulness accelerates degeneration in Gpt2 heterozygous adults.
- Test dietary metabolite supplements that refill tricarboxylic acid cycle intermediates as a rescue for hindlimb motor defects in Gpt2-null mice, modeling spastic paraplegia in GPT2-deficient children.
- Determine how loss of the endosomal sodium/proton exchanger NHE6 blocks endosome-lysosome fusion, and whether this causes faulty retrograde axonal transport and lysosomal deficiency in neurons.
- Define how NHE6 mutant brains acquire disease-associated astrocytes and microglia, and assess tau toxicity in female NHE6 mutation carriers using patient stem cells and an NHE6 carrier rat.
More about the research
Common threads run through the projects: how gene dosage shapes early brain and circuit development, how cell metabolism keeps neurons healthy, and how the cell's internal recycling compartments protect against degeneration. Each project pairs mechanism studies with tests of candidate treatments, linking rare disorders to more common conditions such as autism and Alzheimer's disease.
Why it matters
These studies address conditions that currently have no treatments: autism linked to 17q12 copy number variants, GPT2 deficiency in children, and Christianson syndrome and other NHE6-related disorders. By identifying the metabolic and endosome-lysosome steps that go wrong, the work could point to candidate therapies, including dietary metabolite supplements and Wnt-pathway drugs, and because the same pathways and locus coeruleus vulnerability appear in Alzheimer's disease and related dementias, findings may inform preventive strategies for much more common brain disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Pathogenic Mechanisms in Christianson Syndrome and NHE6-Related Disorders
NIH · Sep 2019 – Jun 2029
Neurodevelopmental mechanisms in 17q12 CNV disorders and autism
NIH · Sep 2024 – Mar 2029
Metabolic Mechanisms in Locus Coeruleus Neuron Vulnerability in Neurodegenerative Disease
NIH · Jun 2024 – Mar 2029
Closest labs
Jennifer Mulle
Rutgers University-New Brunswick, NJ·Genetics
Characterize the full range of traits, sex-dependent risks and co-occurring conditions in 200 new individuals with 3q29 deletion syndrome, using a validated remote phenotyping battery that requires no travel.
David Weinshenker
Emory University, GA·Neuroscience
Determine how neuromelanin, a pigment in norepinephrine neurons, affects locus coeruleus survival in mice, using a viral vector expressing human tyrosinase (hTyr) to make these neurons produce neuromelanin.
Peter Baas
Drexel University, PA·Neuroscience
Test whether lysosome-targeting intrabodies, antibody fragments made inside cells, effectively and sustainably deplete toxic mutant M1 spastin in hiPSC-derived motor cortical organoids without off-target toxicity.
The school
Brown University: 23 labs on PI Pages, $375M a year on research, 251 research doctorates a year.
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