A5025805916- Retinal Development and Disorders
- Mitochondrial Function and Pathology
- Genetic and Kidney Cyst Diseases
- Neuroscience and Neuropharmacology Research
- Retinal Diseases and Treatments
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- ATP Synthase and ATPases Research
- Protist diversity and phylogeny
- Neuroscience and Neural Engineering
- Electrostatic Discharge in Electronics
- Retinal and Macular Surgery
- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- Biomedical Research and Pathophysiology
- Protein Structure and Dynamics
- Blood disorders and treatments
- Protein Kinase Regulation and GTPase Signaling
- Ion channel regulation and function
- Child Abuse and Trauma
- Metabolism and Genetic Disorders
University of Michigan
2020-2023
University of Tennessee Health Science Center
2021
Michigan United
2020
Duke University Hospital
2019
Duke Medical Center
2011-2019
Duke University
2013-2019
Institute of Pharmacology
2017
Inherited retinal degenerations, affecting more than 2 million people worldwide, are caused by mutations in over 200 genes. This suggests that the most efficient therapeutic strategies would be mutation independent, i.e., targeting common pathological conditions arising from many disease-causing mutations. Previous studies revealed one such condition is an insufficiency of ubiquitin-proteasome system to process misfolded or mistargeted proteins affected photoreceptor cells. We now report...
Significance The function of progressive rod-cone degeneration (PRCD) protein has remained a mystery since its gene and associated mutation were discovered as one the most common causes retinal in dogs. Furthermore, numerous mutations have been identified to cause human patients diagnosed with retinitis pigmentosa. Here, we generated PRCD knockout mouse found that functions at site photoreceptor disc morphogenesis where it is required keep newly forming discs flat they protrude from plasma...
The small GTPase Arl3 is important for the enrichment of lipidated proteins to primary cilia, including outer segment photoreceptors. Human mutations in cause both autosomal recessive and dominant inherited retinal dystrophies. We discovered that result increased active G-protein-Arl3-D67V has constitutive activity Arl3-Y90C fast cycling-and their expression mouse rods resulted a displaced nuclear phenotype due an aberrant Arl3-GTP gradient. Using multiple strategies, we go on show removing...
The vertebrate retina has the remarkable ability to support visual function under conditions of limited illumination, including processing signals evoked by single photons. Dim-light vision is regulated several adaptive mechanisms. mechanism explored in this study responsible for increasing light sensitivity and operational range rod bipolar cells, retinal neurons operating immediately downstream photoreceptors. This sensitization achieved through sustained dopamine-dependent GABA release...
Abstract Optic atrophy resulting from retinal ganglion cell (RGC) degeneration is a prominent ocular manifestation of mitochondrial dysfunction. Although transgenic mice lacking the complex I accessory subunit NDUFS4 develop early-onset optic atrophy, severe systemic dysfunction leads to very early death and makes this mouse line impractical for studying pathobiology neuropathies. Theoretically, RGC-specific inactivation ndufs4 would allow characterization RGC over longer time course,...
The primary cilium is a signaling organelle with unique membrane composition maintained by diffusional barrier residing at the transition zone. Many zone proteins, such as tectonic complex, are linked to preserving ciliary but mechanism remains unknown. To understand tectonic's role, we generate photoreceptor-specific Tctn1 knockout mouse. Loss of results in absence entire complex and associated MKS proteins yet has minimal effects on structure rod photoreceptors. We find that protein...
ABSTRACT The small GTPase Arl3 is important for the enrichment of lipidated proteins to primary cilia, including outer segment photoreceptors. Human mutations in cause both autosomal recessive and dominant inherited retinal dystrophies. We discovered that result increased active G-protein—Arl3-D67V has constitutive activity Arl3-Y90C fast cycling—and their expression mouse rods resulted a displaced nuclear phenotype due an aberrant Arl3-GTP gradient. Using multiple strategies, we go on show...