A5074656372- Cancer-related Molecular Pathways
- Retinal Development and Disorders
- Hippo pathway signaling and YAP/TAZ
- Ocular Oncology and Treatments
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Estrogen and related hormone effects
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- SARS-CoV-2 detection and testing
- Photoreceptor and optogenetics research
- Retinoids in leukemia and cellular processes
- Chromatin Remodeling and Cancer
- Photochromic and Fluorescence Chemistry
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Retinal Diseases and Treatments
- SARS-CoV-2 and COVID-19 Research
- Biosensors and Analytical Detection
- Cytokine Signaling Pathways and Interactions
- DNA Repair Mechanisms
Lunenfeld-Tanenbaum Research Institute
2015-2025
Sinai Health System
2016-2025
University of Toronto
2015-2025
Mount Sinai Hospital
2014-2025
Dignity Health
2021
St. Joseph's Hospital and Medical Center
2021
Sichuan University
2021
State Key Laboratory of Biotherapy
2021
Sinai Hospital
2019-2021
University Health Network
2004-2013
Optical coherence tomography (OCT) is a novel method of retinal in vivo imaging. In this study, we assessed the potential OCT to yield histology-analogue sections mouse models degeneration.We achieved adapt commercial 3(rd) generation system obtain and quantify high-resolution morphological retina which so far required vitro histology. histology were compared with developmental defects, light damage, inherited degenerations. conditional knockout mice deficient retinoblastoma protein Rb,...
Abstract Recent advances in cell-free synthetic biology have given rise to gene circuit-based sensors with the potential provide decentralized and low-cost molecular diagnostics. However, it remains a challenge deliver this sensing capacity into hands of users practical manner. Here, we leverage glucose meter, one most widely available point-of-care devices, serve as universal reader for these We describe translator that can convert activation conventional output be read by off-the-shelf...
Emerging evidence suggests that intracellular molecules and organelles transfer between cells during embryonic development, tissue homeostasis disease. We others recently showed transplanted host photoreceptors engage in bidirectional of material the recipient retina, a process termed (MT). used cell transplantation, advanced imaging approaches, genetic pharmacologic interventions primary culture to characterize elucidate mechanism MT. show MT correlates with donor persistence accumulation...
Oncogenic mutations are widespread in normal human tissues1. Similarly, murine chimeras, cells carrying an oncogenic lesion contribute to adult tissues without causing cancer2-4. How lineages that escape cancer via development differ from the minority succumb is unclear. Tumours exhibit characteristic hallmarks; we therefore searched for hallmarks differentiate cancer-prone resistant lineages. Here show total cell cycle duration (Tc) predicts transformation susceptibility across multiple...
It was recently shown that the E2F-pRB complex is a negative transcriptional regulator. However, it not determined whether whole or pRB alone required for repression. Here we show and related protein p107 are capable of direct repression independent E2F. When fused to DNA binding domain GAL4, represses transcription promoters with GAL4 sites. Thus, E2F acts as tether but actively involved in other enhancers. This function maps pocket abrogated by mutation this domain. result suggests an...
Neuronal death evoked by DNA damage requires cyclin-dependent kinase 4 (Cdk4) and 6 activity is accompanied elevation of cyclin D1-associated activity. Because Cdk4/6 phosphorylates retinoblastoma protein (pRb) family members that then modulate the transcriptional E2F/DP1 complexes, we examined involvement these components in damage-evoked neuronal death. Camptothecin induced rapid pRb p107 phosphorylation at a site followed selective loss Rb p107. The CDK inhibitor flavopiridol suppressed...
Multipotent retinal progenitor cells (RPCs) generate various cell types in a precise chronological order, but how exactly cone photoreceptor production is restricted to early stages remains unclear. Here, we show that the POU-homeodomain factors Pou2f1/Pou2f2, homologs of Drosophila temporal identity nub/pdm2, regulate timely cones mice. Forcing sustained expression Pou2f1 or Pou2f2 RPCs expands period production, whereas misexpression late-stage triggers ectopic at expense late-born fates....
Abstract Population scale sweeps of viral pathogens, such as SARS-CoV-2, require high intensity testing for effective management. Here, we describe “Systematic Parallel Analysis RNA coupled to Sequencing Covid-19 screening” (C19-SPAR-Seq), a multiplexed, scalable, readily automated platform SARS-CoV-2 detection that is capable analyzing tens thousands patient samples in single run. To address strict requirements control assay parameters and output demanded by clinical diagnostics, employ...
Systematically investigating the scores of genes mutated in cancer and discerning disease drivers from inconsequential bystanders is a prerequisite for precision medicine but remains challenging. Here, we developed somatic CRISPR/Cas9 mutagenesis screen to study 215 recurrent "long-tail" breast genes, which revealed epigenetic regulation as major tumor-suppressive mechanism. We report that components BAP1 COMPASS-like complexes, including KMT2C/D, KDM6A, BAP1, ASXL1/2 ("EpiDrivers"),...
Small cell lung cancer (SCLC) is an aggressive disease with overall five-year survival rate of <10%. Treatment for SCLC cisplatin/etoposide chemotherapy (C/E) +/- radiotherapy (RT) has changed modestly over several decades. The ubiquitin-proteasome system underexplored therapeutic target SCLC. We preclinically evaluated TAK-243, a first-in-class small molecule E1 inhibitor against UBA1.We assessed TAK-243 in 26 cell-lines as monotherapy and combined C/E, the PARP-inhibitor, olaparib,...
Semliki Forest virus (SFV) vectors can be produced faster, and have a wider host range, than baculovirus vectors. However, the original SFV system requires <i>in vitro</i>manipulation of RNA. We generated that is wholly DNA-based. Both replicon vector, encoding polymerase protein interest, helper viral structural proteins, were modified so expression was RNA II-dependent. Transfection plasmid alone 20–30-fold more obtained from simple vector. Expression required replicase, which amplifies...
In the Chx10 -null ocular retardation (or J ) mouse, retinal progenitor cell (RPC) proliferation is impaired, and bipolar neurons, a late born type, fail to differentiate. It unclear whether required maintain throughout retinogenesis or defect an indirect effect of growth arrest. We show that dispensable for late-stage RPC but essential promote genesis in place rods. Ectopic expression drove instead rod differentiation without affecting division. Converting activator impaired...
IFN-gamma induction of the CIITA (class II transactivator) promoter (pIV) requires Brahma-related gene 1 (BRG1), a chromatin-remodeling enzyme. However, events that lead to pIV activation are only partially understood, and point at which BRG1 acts is unknown. The first IFN-gamma-induced event triggers nuclear translocation STAT1 (signal transducer activator transcription 1), binds IFN-gamma-responsive promoters. recruited after binding several other inducible loci, STAT family members known...
The retinoblastoma gene product, p110RB1, appears to regulate cell growth by modulating the activities of nuclear transcription factors. elements that specify transport p110RB1 into nucleus have not yet been explored. We now report identification a basic region, KRSAEGGNPPKPLKKLR, in C terminus which has sequence similarity known bipartite localization signals (NLSs). A two-amino-acid mutation introduced this putative NLS [to give mutant NLS(NQ)] or deletion entire (delta NLS) abrogated...