A5002168770- Glaucoma and retinal disorders
- Retinal Development and Disorders
- Protease and Inhibitor Mechanisms
- Mitochondrial Function and Pathology
- Orthopaedic implants and arthroplasty
- Metabolomics and Mass Spectrometry Studies
- Retinal Diseases and Treatments
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- Blood Coagulation and Thrombosis Mechanisms
- Bone health and treatments
- Calpain Protease Function and Regulation
- Ubiquitin and proteasome pathways
- Bone health and osteoporosis research
- Epigenetics and DNA Methylation
- Neurological Disorders and Treatments
- CRISPR and Genetic Engineering
- Nicotinic Acetylcholine Receptors Study
- Pulmonary Hypertension Research and Treatments
- Neurogenetic and Muscular Disorders Research
Aix-Marseille Université
2021
Jackson Laboratory
2017-2020
Howard Hughes Medical Institute
2017-2018
University of Massachusetts Chan Medical School
2015-2018
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; survival in ALS typically 3–5 years. No treatment extends patient by more than three months. Approximately 20% of familial and 1–3% sporadic patients carry mutation the gene encoding superoxide dismutase 1 (SOD1). In transgenic mouse model expressing mutant SOD1G93A protein, silencing SOD1 prolongs survival. One study reports therapeutic effect systemically treated adult mice; this was achieved with short hairpin RNA,...
Significance Age-related bioenergetic insufficiency increases the vulnerability of retinal ganglion cells to intraocular pressure during glaucoma pathogenesis. This paper addresses these relationships and provides a deeper understanding this common neurodegeneration. We demonstrate an pressure-dependent decline in pyruvate levels coupled dysregulated glucose metabolism, detected mTOR activation at mechanistic nexus neurodegeneration metabolism. Supporting this, oral supplementation or...
Glaucoma is a complex neurodegenerative disease characterized by progressive visual dysfunction leading to vision loss. Retinal ganglion cells are the primary affected neuronal population, with critical insult damaging their axons in optic nerve head. This typically secondary harmfully high levels of intraocular pressure (IOP). We have previously determined that early mitochondrial abnormalities within retinal lead dysfunction, age-related declines NAD (NAD+ and NADH) rendering cell...
Significance Chronic obstructive pulmonary disease affects 10% of the worldwide population, and leading genetic cause is a disease, α-1 antitrypsin (AAT) deficiency. Humans have only one gene that codes for AAT protein, but mice up to six, which made it impossible decades create mouse model disease. Here we succeeded in creating this using CRISPR technology target all genes at once. Importantly, spontaneously develops lung recapitulates many aspects human We anticipate will be highly...
Nicotinamide adenine dinucleotide (NAD) is a key molecule in several cellular processes and essential for healthy mitochondrial metabolism. We recently reported that dysfunction among the very first changes to occur within retinal ganglion cells during initiation of glaucoma DBA/2J mice. Furthermore, we demonstrated an age-dependent decline NAD contributes vulnerability glaucoma. The decrease renders vulnerable metabolic crisis following periods high intraocular pressure. Treating mice with...
Abstract Intraocular pressure-sensitive retinal ganglion cell degeneration is a hallmark of glaucoma, the leading cause irreversible blindness. Converging evidence indicates that age-related bioenergetic insufficiency increases vulnerability cells to intraocular pressure. To investigate further, we used metabolomics and RNA-sequencing examine early glaucoma in DBA/2J mice. We demonstrate an pressure-dependent decline pyruvate levels coupled dysregulated glucose metabolism prior detectable...
Alpha-one antitrypsin (AAT) deficiency is a common autosomal co-dominant genetic disorder. This condition affects 1:2500 individuals of European ancestry, leading to the development lung and liver disease. Within North American Northern populations, an estimated 4% are carriers mutant alleles. AAT presents with emphysema phenotype in lungs older subjects. deficient subjects can also suffer from disease varying severity; however, principle cause death. protease inhibitor predominantly...