A5021655948- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Zebrafish Biomedical Research Applications
- Angiogenesis and VEGF in Cancer
- Histone Deacetylase Inhibitors Research
- Retinoids in leukemia and cellular processes
- Corneal Surgery and Treatments
- Photoreceptor and optogenetics research
- Ocular Oncology and Treatments
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- Photochromic and Fluorescence Chemistry
- Cancer, Hypoxia, and Metabolism
- Receptor Mechanisms and Signaling
- Glaucoma and retinal disorders
- Retinopathy of Prematurity Studies
- Genetic and Kidney Cyst Diseases
- Protein Degradation and Inhibitors
- Connexins and lens biology
- CRISPR and Genetic Engineering
- Click Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Esophageal Cancer Research and Treatment
- bioluminescence and chemiluminescence research
University College Dublin
2016-2025
Mayo Clinic
2023
Conway School of Landscape Design
2017-2019
Trinity College Dublin
2013
St. James's Hospital
2013
Harvard University
2009
University of Notre Dame
2001-2007
University of Washington
2001-2003
Howard Hughes Medical Institute
2001
Adirondack Medical Center
1998
The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina most mammals. Developmental abnormalities or microvascular complications in result severe human eye diseases lead to blindness. To exploit advantages zebrafish for genetic, developmental and pharmacological studies vasculature, we characterised intraocular zebrafish.We show detailed morphological analysis supply zebrafish. Similar transient hyaloid mammalian embryos, are first found attached lens...
SUMMARY. Approximately 2.5 million people worldwide are clinically blind because of diabetic retinopathy. In the non-proliferative stage, pathophysiology this ocular manifestation diabetes presents as morphological and functional disruption retinal vasculature, dysfunction neurons. However, it is uncertain whether vascular neuronal changes interdependent or independent events. addition, identity neurons that most susceptible to hyperglycaemia associated with unclear. Here, we characterise a...
Abstract Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These cause irreversible vision loss, provide a significant health economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% patients non-responsive these drugs they associated with ocular systemic side effects. Therefore, there is need...
Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa Bardet-Biedl syndrome (BBS), frequently affecting many physiological processes across multiple organs. Cilium formation, maintenance function depend on intracellular transport systems intraflagellar (IFT), which is driven by kinesin-2 IFT-dynein motors regulated...
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed our immunohistochemistry studies on HDAC6 overexpression in tissues. We herein developed series of novel hHDAC6 inhibitors, having low inhibitory potency over hHDAC1 and hHDAC8, as potential pharmacological tools for treatment. Their was combined vitro vivo toxicity. Structural analysis 6h structure–activity...
Uveal melanoma (UM) is an ocular cancer, with propensity for lethal liver metastases. When metastatic UM (MUM) occurs, as few 8% of patients survive beyond two years. Efficacious treatments MUM are urgently needed. 1,4-dihydroxy quininib, a cysteinyl leukotriene receptor 1 (CysLT
Transducins couple visual pigments to cGMP hydrolysis, the only recognized phototransduction pathway in vertebrate photoreceptors. Here we describe a zebrafish mutant, no optokinetic response f(w21) (nof), with nonsense mutation gene encoding alpha subunit of cone transducin. Retinal morphology and levels enzymes are normal nof retinas, but transducin is undetectable. Dark current cones also normal, it insensitive moderate intensity light. The do respond, however, bright These responses...
To identify in vivo a promoter fragment that specifically directs transgene expression all zebrafish cone photoreceptors. This subsequently enables GFP labeling of cones for facile morphologic analysis and purification genetic rescue achromatopsia.Promoter fragments the transducin alpha (TalphaC) gene were subcloned upstream EGFP microinjected into one- to two-cell-stage embryos. Promoter activity was assessed by fluorescence microscopy wholemounts retinal cryosections, photoreceptors...
Ocular neovascularisation is a pathological hallmark of some forms debilitating blindness including diabetic retinopathy, age related macular degeneration and retinopathy prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition the pro-angiogenic factor VEGF. However, targeting angiogenic pathways other than, in combination to VEGF, may lead more effective safer inhibitors intraocular angiogenesis. In small chemical screen using...
Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye malformations that cause a significant proportion of childhood visual impairments. Several disease genes have been identified but do not account for all MAC cases, suggesting additional risk loci exist. We used single nucleotide polymorphism (SNP) homozygosity mapping (HM) targeted next-generation sequencing to identify the causative mutation autosomal recessive isolated colobomatous microanophthalmia (MCOPCB) in...
Retinal diseases, such as hereditary retinitis pigmentosa and age-related macular degeneration, are characterized by the progressive loss of photoreceptors. Histone deacetylase 6 (HDAC6) is considered a stress surveillance factor potential target for neuroprotection regeneration. Overexpression HDAC6 has been connected to neurodegenerative disorders, its suppression may provide protection. Here we show that constitutively present in mouse retina, cone-like cell line 661W. In 661W cells...
Cilia both receive and send information, the latter in form of extracellular vesicles (EVs). EVs are nano-communication devices that influence cell, tissue, organism behavior. Mechanisms driving ciliary EV biogenesis almost entirely unknown. Here, we show G-protein Rab28, associated with human autosomal recessive cone-rod dystrophy, negatively regulates levels sensory organs Caenorhabditis elegans a cilia specific manner. Sequential targeting lipidated Rab28 to periciliary membranes is...
BackgroundAlthough neoangiogenesis is a hallmark of chronic inflammatory diseases such as arthritis and many cancers, therapeutic agents targeting the vasculature remain elusive. Here we identified miR-125a an important regulator angiogenesis.MethodsMiRNA levels were quantified in Psoriatic Arthritis (PsA) synovial-tissue by RT-PCR compared to macroscopic synovial vascularity. HMVEC transfected with anti-miR-125a angiogenic mechanisms using tube formation assays, transwell invasion chambers,...
The anticancer drug candidate (1-methyl-3-(p-cyanobenzyl)benzimidazole-2-ylidene)silver(I)acetate (SBC1) was tested in vitro against human neuroblastoma cells, UKF-NB-3 and UKF-NB-6, delivering IC50 values of 29 +/- 5 4 μM, while further testing cisplatin-, carboplatin- oxaliplatin-resistant UKF-NB-3/6 sub-lines showed no cross-resistance with respect to SBC1. A similar trend found for SBC1 the colon carcinoma cell line HCT8 an value 3.1 0.9 μM; again able break cisplatin-...
Background and Purpose Pathological growth of ocular vasculature networks can underpin visual impairment in neovascular age‐related macular degeneration, proliferative diabetic retinopathy prematurity. Our aim was to uncover novel pharmacological regulators angiogenesis by phenotype‐based screening zebrafish. Experimental Approach A bioactive chemical library 465 drugs screened identify small molecule inhibitors hyaloid (HV) zebrafish larvae. Selectivity assessed evaluation non‐ocular...