A5061327619- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Retinal Diseases and Treatments
- Epigenetics and DNA Methylation
- Renal and related cancers
- Advanced biosensing and bioanalysis techniques
- TGF-β signaling in diseases
- Tissue Engineering and Regenerative Medicine
- Cancer-related gene regulation
- Phosphodiesterase function and regulation
- DNA Repair Mechanisms
- Receptor Mechanisms and Signaling
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neuropharmacology Research
- Prenatal Screening and Diagnostics
- Neuroinflammation and Neurodegeneration Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
- Ubiquitin and proteasome pathways
- Acute Kidney Injury Research
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
Columbia University Irving Medical Center
2015-2025
Columbia University
2013-2024
Royal College of Physicians
2008-2023
Herbert Irving Comprehensive Cancer Center
2008-2023
Cancer Research Center
2012-2013
Cancer Genetics (United States)
2012
Sylvester Comprehensive Cancer Center
2008
Ophthalmology Associates (United States)
2006
Target (United States)
2002
National Institutes of Health
2001
Complementary sets of genes are epigenetically silenced in male and female gametes a process termed genomic imprinting. The Dnmt3L gene is expressed during gametogenesis at stages where imprints established. Targeted disruption caused azoospermia homozygous males, heterozygous progeny females died before midgestation. Bisulfite sequencing DNA from oocytes embryos showed that removal prevented methylation sequences normally maternally methylated. defect was specific to imprinted regions,...
ABSTRACT GATA-1 is a zinc-finger transcription factor believed to play an important role in gene regulation during the development of erythroid cells, megakaryocytes and mast cells. Other members GATA family, which can bind same DNA sequence motif, are co-expressed several these hemopoietic lineages, raising possibility overlap function. To examine specific roles hematopoietic cell differentiation, we have tested ability embryonic stem carrying targeted mutation X-linked gene, contribute...
Erythropoietin, known for its role in erythroid differentiation, has been shown to be neuroprotective during brain ischaemia adult animal models. Although high levels of erythropoietin receptor are produced embryonic brain, the development is uncertain. We now provide evidence that acts stimulate neural progenitor cells and prevent apoptosis brain. Mice lacking exhibit severe anaemia defective cardiac development, die at day 13.5 (E13.5). By E12.5, addition foetal liver, endocardium...
MACF1 (microtubule actin cross-linking factor 1) is a multidomain protein that can associate with microfilaments and microtubules. We found was highly expressed in neuronal tissues the foregut of embryonic day 8.5 (E8.5) embryos head fold primitive streak E7.5 embryos. −/− mice died at gastrulation stage displayed developmental retardation defects formation streak, node, mesoderm. This phenotype similar to Wnt-3 LRP5/6 double-knockout In absence Wnt, associated complex contained Axin,...
α–Intercalated cells (A-ICs) within the collecting duct of kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in defense against urinary infections. In a murine tract infection model, bound uropathogenic E. coli responded by acidifying urine secreting bacteriostatic protein lipocalin 2 (LCN2; known NGAL). A-IC–dependent LCN2 secretion required TLR4, mice expressing an LPS-insensitive form TLR4 expressed reduced levels...
Ataxia telangiectasia (A-T) mutated (ATM) kinase orchestrates deoxyribonucleic acid (DNA) damage responses by phosphorylating numerous substrates implicated in DNA repair and cell cycle checkpoint activation. A-T patients mouse models that express no ATM protein undergo normal embryonic development but exhibit pleiotropic defects. In this paper, we report mice carrying homozygous kinase-dead mutations Atm (AtmKD/KD) died during early development. AtmKD/− cells exhibited proliferation defects...
Massive parallel sequencing enables identification of numerous genetic variants in mutant organisms, but determining pathogenicity any one mutation can be daunting. The most commonly studied preclinical model retinitis pigmentosa called the "rodless" (rd1) mouse is homozygous for two mutations: a nonsense point (Y347X) and an intronic insertion leukemia virus (Xmv-28). Distinguishing which causes retinal degeneration still under debate nearly century after discovery this organism. Here, we...
Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin deteriorate, eventually cell death and, consequently, loss vision. Here, we have hypothesized associated with mutations in phosphodiesterase-6 (PDE6) provokes metabolic aberration rod cells promotes the pathological consequences elevated cGMP Ca2+, which are induced by Pde6 mutation. Inhibition...
Quiescent neural stem cells (NSCs) in the adult mouse ventricular-subventricular zone (V-SVZ) undergo activation to generate neurons and some glia. Here we show that platelet-derived growth factor receptor beta (PDGFRβ) is expressed by V-SVZ NSCs olfactory bulb interneurons Selective deletion of PDGFRβ leads their release from quiescence, uncovering gliogenic domains for different glial cell types. These are also recruited upon injury. We identify an intraventricular oligodendrocyte...
Abstract Loss of TGFBI, a secreted protein induced by transforming growth factor-β, has been implicated in cell proliferation, tumor progression, and angiogenesis vitro studies. However, vivo antitumor functions TGFBI as well the underlying molecular mechanism are not understood. To these aims, we have generated mouse model with disruption genomic locus. Mice lacking show retarded prone to spontaneous tumors 7,12-dimethylbenz(a)anthracene–induced skin tumors. In relation wild-type (WT)...
Hereditary retinal degenerative diseases, such as retinitis pigmentosa (RP), are characterized by the progressive loss of rod photoreceptors followed cones. While gene therapy clinical trials demonstrated temporary improvement in visual function, this approach has yet to achieve sustained functional and anatomical rescue after disease onset patients. The lack benefit could be due insufficient transduction efficiency viral vectors ("too little") and/or because is too advanced late") at time...
Abstract Pparg , a nuclear receptor, is downregulated in basal subtype bladder cancers that tend to be muscle invasive and amplified luminal non-muscle invasive. Bladder derive from the urothelium, one of most quiescent epithelia body, which composed basal, intermediate, superficial cells. We find expression an activated form ( VP16;Pparg ) progenitors induces formation cells situ, exit cell cycle, do not tumors. Expression have been by mild injury however, results tumor formation. these...
Retinitis pigmentosa (RP) is one of the most common forms hereditary neurodegeneration. It caused by or more at least 3,100 mutations in over 80 genes that are primarily expressed rod photoreceptors. In RP, primary rod-death phase followed cone death, regardless underlying gene mutation drove initial degeneration. Dampening oxidation glycolytic end products mitochondria enhances survival divergent etiological disease models independent rod-specific mutations. Therapeutic editing prolyl...
PKC-interacting protein (PKCI), also designated histidine triad nucleotide-binding 1, belongs to the (HIT) family of proteins. Its structure is highly conserved from bacteria humans and shares homology with tumor-suppressor gene fragile (FHIT). Although it was originally thought inhibit PKC, its actual physiologic function not known. Therefore, we used technique homologous recombination generate homozygous deleted PKCI -/- mice. These mice display normal fetal adult development. However,...
Production of protein containing lengthy stretches polyglutamine encoded by multiple repeats the trinucleotide CAG is a hallmark Huntington's disease (HD) and variety other inherited degenerative neurological neuromuscular disorders. Earlier work has shown that interference with production transcription elongation SUPT4H results in decreased cellular capacity to transcribe mutant huntingtin gene (Htt) alleles long expansions, but little effect on expression genes short stretches. zQ175 R6/2...
Abstract Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the version genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve technology, compare light-dimerization optimize for mammalian using a CAG promoter, Magnets, 2A self-cleaving peptide. prevent background recombination caused by high sequence similarity in dimerization domains, modify codons mouse targeting...
Mutations in rhodopsin (RHO) are the most common causes of autosomal dominant retinitis pigmentosa (adRP), accounting for 20% to 30% all cases worldwide. However, high degree genetic heterogeneity makes development effective therapies cumbersome. To provide a universal solution RHO-related adRP, we devised CRISPR-based, mutation-independent gene ablation and replacement (AR) compound therapy carried by dual AAV2/8 system. Moreover, developed novel hRHO