A5064716959- Hereditary Neurological Disorders
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Pain Mechanisms and Treatments
- Botulinum Toxin and Related Neurological Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Cephalopods and Marine Biology
- Heat shock proteins research
- Toxin Mechanisms and Immunotoxins
- Genetic Syndromes and Imprinting
- Nerve injury and regeneration
- Neurological diseases and metabolism
- Peripheral Neuropathies and Disorders
- RNA Research and Splicing
- RNA modifications and cancer
- Veterinary Pharmacology and Anesthesia
- Endoplasmic Reticulum Stress and Disease
- Mosquito-borne diseases and control
- Pharmacological Effects and Assays
University of North Carolina at Chapel Hill
2020-2024
University of Florida
2017-2019
Allen Institute for Brain Science
2019
Abstract Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace (http://painface.net) that uses machine learning detect 4 facial action units the mouse grimace scale (orbitals, nose, ears, whiskers) score grimaces black-coated C57BL/6 male female 0 8 scale. Platform accuracy was validated 2 laboratories, 3 conditions evoke...
The absence of functional peripheral myelin protein 22 (PMP22) is associated with shortened lifespan in rodents and severe nerve abnormalities several species including humans. Schwann cells nerves from PMP22 knock-out (KO) mice show deranged cholesterol distribution aberrant lipid raft morphology, supporting an unrecognized role for cellular metabolism. To examine the mechanisms underlying these abnormalities, we studied male female KO mice. Whole-cell current-clamp recordings cultured...
A common form of hereditary autosomal dominant demyelinating neuropathy known as Charcot-Marie-Tooth disease type 1A (CMT1A) is linked with duplication the peripheral myelin protein 22 (PMP22) gene. Although studies from animal models have led to better understanding pathobiology these neuropathies, there continues be a gap in translation findings rodents humans. Because PMP22 was originally identified fibroblasts growth arrest specific gene 3 (gas3) and expressed broadly body, it tested...
Charcot-Marie-Tooth (CMT) diseases comprise a genetically heterogeneous group of hereditary peripheral neuropathies. Trembler J (TrJ) mice carry spontaneous mutation in myelin protein 22 (PMP22) and model early-onset, severe CMT type 1E disease. Recent studies indicate that phospholipid substitution, or cholesterol-enriched diet, benefit myelinated nerves, however such interventions have not been tested early-onset dysmyelinating Here, we examined the lipid profile nerves from 6-month-old...
The majority of hereditary neuropathies are caused by duplication the peripheral myelin protein 22 (PMP22) gene. Therefore, mechanisms to suppress expression PMP22 gene have high therapeutic significance. Here we asked whether human is a target for regulation microRNA 29a (miR-29a). Using bioinformatics, determined that contains conserved seed sequence miR-29a binding site and this regulatory motif included in duplicated region neuropathic patients. luciferase reporter assays HEK293 cells,...
Hereditary demyelinating neuropathies linked to peripheral myelin protein 22 (PMP22) involve the disruption of normal trafficking and are therefore relevant targets for chaperone therapy. Using a small molecule HSP90 inhibitor, EC137, in cell culture models, we previously validated pathway as viable target therapy development. Here, tested five commercially available inhibitors identified BIIB021 AUY922 support Schwann viability enhance expression. showed higher efficacy, compared BIIB021,...
Gene-editing technologies promise to create a new class of therapeutics that can achieve permanent correction with single intervention. Besides eliminating mutant alleles in familial disease, gene-editing also be used favorably manipulate upstream pathophysiologic events and alter disease-course wider patient populations, but few such feasible therapeutic avenues have been reported. Here we use CRISPR-Cas9 edit the last exon amyloid precursor protein (