A5040053099- Nerve injury and regeneration
- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Retinal Imaging and Analysis
- Neurogenesis and neuroplasticity mechanisms
- Signaling Pathways in Disease
- Pluripotent Stem Cells Research
- Neuropeptides and Animal Physiology
- Neuroinflammation and Neurodegeneration Mechanisms
- 14-3-3 protein interactions
- Complement system in diseases
- Neuroblastoma Research and Treatments
- Retinoids in leukemia and cellular processes
- Glaucoma and retinal disorders
- Axon Guidance and Neuronal Signaling
- Virus-based gene therapy research
- Alzheimer's disease research and treatments
- CRISPR and Genetic Engineering
- Receptor Mechanisms and Signaling
- Wound Healing and Treatments
- Supramolecular Self-Assembly in Materials
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- 3D Printing in Biomedical Research
- Biochemical and Structural Characterization
University of California, Santa Barbara
2013-2024
Johns Hopkins Medicine
2002
Johns Hopkins University
2002
Centro de Investigaciones Biológicas Margarita Salas
1998
Neuroscience Institute
1997
Amgen (United States)
1994
Stanford University
1986-1991
Brandeis University
1986
University of Wisconsin–Madison
1986
Stanford Medicine
1986
In newborn rats the levels of nerve growth factor (NGF) mRNA (mRNANGF) and NGF receptor (mRNA(rec)) in sciatic were 10 120 times higher, respectively, than adult animals. mRNA(rec) decreased steadily from birth, approaching by third postnatal week, whereas mRNANGF only after first although also reaching week. Transection resulted a marked biphasic increase with time. On proximal side cut, this was confined to area immediately adjacent cut; peripherally, similar present all segments. markedly...
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older individuals worldwide. The disease characterized by abnormal extracellular deposits, known as drusen, that accumulate along the basal surface retinal pigmented epithelium. Although drusen deposition common individuals, large numbers and/or extensive areas confluent represent significant risk factor for AMD. Widespread associated with epithelial cell dysfunction and photoreceptor cells neural...
The TrkB family of transmembrane proteins serve as receptors for brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-4/5, and possibly NT-3, three members the factors. In order to understand potential roles played by these receptors, we have examined distribution receptor in adult rat brain using immunohistochemistry. Several different antisera, directed against either synthetic peptides corresponding regions or a recombinant fusion protein comprising part extracellular domain, were...
Abstract Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation sub-RPE deposits, AMD leads to progressive degeneration, in advanced cases, irreversible vision loss. Although genetic analysis, animal models, cell culture systems have yielded important insights into AMD, molecular pathways underlying AMD's onset progression...
The neurotrophins brain-derived neurotrophic factor (BDNF) and NT-4/5 exert their trophic effects on the nervous system via signaling through trkB receptors. These receptors occur as splice variants of gene that encodes a full-length receptor containing signal transducing tyrosine kinase domain well truncated forms lacking this domain. Because importance isoforms for development maturation is unknown, we have examined expression during rat forebrain using 1) sensitive ribonuclease protection...
Abstract Investigations into the biological actions of nerve growth factor (NGF) have shown that dorsal root ganglion (DRG) neurons subserving nociception require NGF for survival and maintenance phenotype. This discovery suggests signaling receptor, TrkA, can be used as a marker nociceptive neurons. In this study, we antibodies to in conjunction with cell markers show restricted distribution DRG, further characterize subsets DRG are dependent upon NGF. Staining TrkA labeled small...
Tau is a neuronal microtubule-associated protein that promotes microtubule assembly, stability, and bundling in axons. Two distinct regions of tau are important for the tau-microtubule interaction, relatively well-characterized "repeat region" carboxyl terminus (containing either three or four imperfect 18-amino acid repeats separated by 13- 14-amino long inter-repeats) more centrally located, poorly characterized proline-rich region. By using amino-terminal truncation analyses tau, we have...
Variants in the complement factor H gene (CFH) are associated with age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5) lie within regulators of activation (RCA) locus on chromosome 1q32. Aims Methods. In this study, structural evolutionary relationships between these AMD was refined using a combined genetic, molecular immunohistochemical approach.We identify characterize large, common deletion that encompasses both CFHR1 CFHR3 genes. CFHR1, an abundant serum...
The trkB family of transmembrane proteins serves as receptors for BDNF and NT-4/5. is composed a tyrosine kinase-containing isoform well several alternatively spliced “truncated receptors” with identical extracellular ligand-binding domains but very small intracellular domains. two best-characterized truncated receptors, designated trkB.T1 trkB.T2, contain only 23 21 amino acids, respectively. Although it known that the kinase (trkB.FL) capable initiating NT-4/5-induced signal transduction,...
Polymorphisms in the complement factor H gene (CFH) are associated with a significantly increased risk for, or protection against, development of age-related macular degeneration (AMD). The most documented risk-conferring single-nucleotide polymorphism results tyrosine-to-histidine substitution at position 402 (Y402H) CFH protein. In this work, we examined ocular distributions and relative abundance CFH, several CFH-binding proteins, abundant serum proteins retinal pigmented epithelium...
We introduce a human retinal pigmented epithelial (RPE) cell-culture model that mimics several key aspects of early stage age-related macular degeneration (AMD). These include accumulation sub-RPE deposits contain molecular constituents drusen, and activation complement leading to formation deposit-associated terminal complexes. Abundant are rich in apolipoprotein E (APOE), prominent drusen constituent, formed by RPE cells grown on porous supports. Exposure serum results selective,...
Significance Recessive Stargardt macular degeneration (STGD1) and a subset of cone–rod dystrophies are caused by mutations in the Abca4 gene. The ABCA4 protein is flippase photoreceptor cells that helps eliminate retinaldehyde, toxic photoproduct vision. Here we found additionally present retinal pigment epithelium (RPE) mice at approximately 1% its abundance neural retina. Genetically modified express RPE but not showed partial rescue both lipofuscin accumulation observed −/− STGD1...
Sensory neurons of the adult rat dorsal root ganglion (DRG) can be maintained in culture absence nerve growth factor (NGF). We have thus used dissociated cultures these to study effects NGF on regulation expression mRNA encoding receptor (NGF-R). In NGF, levels NGF-R remained constant for 7 days DRG neurons. presence rose two - three-fold after 2 days, reaching plateau (five six-fold elevation) 5 days. This NGF-induced up-regulation could demonstrated even prior NGF-deprivation 3 4 had no...
Measles virus (MV) lacking expression of C protein (C(KO)) is a potent activator the double-stranded RNA (dsRNA)-dependent kinase (PKR), whereas isogenic parental expressing not. Here, we demonstrate that significant amounts dsRNA accumulate during C(KO) mutant infection but not following infection. accumulated late stages and localized with replication sites containing N P proteins. PKR autophosphorylation stress granule formation correlated timing appearance. Phospho-PKR to...
Vitamin D has been shown to have anti-angiogenic properties and play a protective role in several types of cancer, including breast, prostate cutaneous melanoma. Similarly, vitamin levels be for risk number conditions, cardiovascular disease chronic kidney disease, as well numerous autoimmune disorders such multiple sclerosis, inflammatory bowel diseases type 1 diabetes mellitus. A study performed by Parekh et al. was the first suggest age-related macular degeneration (AMD) showed...
Human embryonic stem cells (hESCs) offer a potentially unlimited supply of for emerging cell-based therapies. Unfortunately, the process deriving distinct cell types can be time consuming and expensive. In developed world, age-related macular degeneration (AMD) is leading cause blindness in elderly, with more than 7.2 million people afflicted U.S. alone. Both hESC-derived retinal pigmented epithelium (hESC-RPE) induced pluripotent cell-derived RPE (iPSC-RPE) are being AMD therapies by...
Neurotrophins play important roles in the survival, differentiation, and maintenance of CNS neurons. To begin to investigate specific for these factors mammalian visual system, we have examined cellular localization neurotrophin receptor trkB within developing cerebral cortex thalamus ferret using extracellular domain-specific antibodies. At prenatal ages (gestation is 41 d), trkB-immunostained fibers were observed internal capsule as two distinct fascicles intermediate zone cortex. The...
The interaction between tubulin subunits and microtubule-associated proteins (MAPs) such as tau is fundamental for microtubule structure function. Previous work has suggested that the "microtubule binding domain" of (composed three or four imperfect 18-amino acid repeats, separated by 13- 14-amino inter-repeat regions) can bind to C-terminal ends both α β monomers. Here, using covalent cross-linking strategies, we demonstrate there are two distinct sites (designated "C-terminal" "internal")...