A5072670177- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Estrogen and related hormone effects
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- NF-κB Signaling Pathways
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Autophagy in Disease and Therapy
- Neurobiology and Insect Physiology Research
- Immune Response and Inflammation
- Microtubule and mitosis dynamics
- PI3K/AKT/mTOR signaling in cancer
- Glioma Diagnosis and Treatment
- Pancreatic function and diabetes
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Insects and Parasite Interactions
University Health Network
2015-2025
Princess Margaret Cancer Centre
2013-2025
University of Toronto
1999-2022
Hospital for Sick Children
1999-2022
Great Ormond Street Hospital
2022
University College London
2022
SickKids Foundation
2022
Health Net
2019
Center for Cancer Research
2018
Harvard University
2018
The mature mammalian retina is thought to lack regenerative capacity. Here, we report the identification of a stem cell in adult mouse eye, which represents possible substrate for retinal regeneration. Single pigmented ciliary margin cells clonally proliferate vitro form sphere colonies that can differentiate into retinal-specific types, including rod photoreceptors, bipolar neurons, and Müller glia. Adult are localized not central peripheral epithelium, indicating these may be homologous...
FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 called Fas). CD95, tumor necrosis factor type 1 (TNFR-1), and 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A c- myc , chemotherapeutic agent adriamycin did. Mice with deletion the gene survive beyond day 11.5 embryogenesis; these mice showed signs cardiac failure abdominal hemorrhage. Chimeric embryos showing high contribution null mutant cells to...
Neural stem cells, which exhibit self-renewal and multipotentiality, are generated in early embryonic brains maintained throughout the lifespan. The mechanisms of their generation maintenance largely unknown. Here, we show that neural cells independent RBP-J κ, a key molecule Notch signaling, by using κ −/− an cell-derived neurosphere assay. However, pathway molecules essential for cells; they depleted or Notch1 mice. also deficient presenilin1 ( PS1 ) gene, regulator reduced +/− adult...
Mutations in the SMAD4/DPC4 tumor suppressor gene, a key signal transducer most TGFβ-related pathways, are involved 50% of pancreatic cancers. Homozygous Smad4 mutant mice die before day 7.5 embryogenesis. Mutant embryos have reduced size, fail to gastrulate or express mesodermal marker, and show abnormal visceral endoderm development. Growth retardation -deficient results from cell proliferation rather than increased apoptosis. Aggregation ES cells with wild-type tetraploid morulae rescues...
Phosphorylation of IκB, an inhibitor NF-κB , is important step in the activation transcription factor . mediated by IκB kinase (IKK) complex, known to contain two catalytic subunits: IKKα and IKKβ A novel, noncatalytic component this complex called NEMO ( N F-κB e ssential mo dulator)/ IKKγ was identified recently. We have generated NEMO/IKKγ -deficient mice gene targeting. Mutant embryos die at E12.5–E13.0 from severe liver damage due apoptosis. primary murine embryonic fibroblasts (MEFs)...
Tumor cells gain a survival/growth advantage by adapting their metabolism to respond environmental stress, process known as metabolic transformation. The best-known aspect of transformation is the Warburg effect, whereby cancer up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), brain-specific enzyme, may participate in CPT1C expression correlates inversely with mammalian target...
Diverse functions have been reported for lipocalin 2. To investigate these in vivo , we generated gene-targeted 2-deficient mice ( Lcn2 −/− mice). In vitro studies suggested that 2 is important cellular apoptosis induced by IL-3 withdrawal, and the induction of kidney differentiation during embryogenesis. Analysis showed normal cell death upon withdrawal development. However, found exhibited an increased susceptibility to bacterial infections, keeping with proposed function iron...
Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31), a member of the Ig superfamily, is expressed strongly at endothelial cell-cell junctions, on platelets, and most leukocytes. CD31 has been postulated to play role in vasculogenesis angiogenesis, implicated as key mediator transendothelial migration To further define physiologic CD31, we used targeted gene disruption embryonic stem cells generate CD31-deficient mice. mice (CD31KO) are viable born expected Mendelian frequency,...
In response to ionizing radiation (IR), the tumor suppressor p53 is stabilized and promotes either cell cycle arrest or apoptosis.Chk2 activated by IR contributes this stabilization, possibly direct phosphorylation.Like p53, Chk2 mutated in patients with Li-Fraumeni syndrome.Since ataxia telangiectasia (ATM) gene required for IR-induced activation of Chk2, it has been assumed that ATM act a linear pathway leading activation.To clarify role tumorigenesis, we generated genetargeted...
Isocitrate dehydrogenase-1 ( IDH1 ) R132 mutations occur in glioma, but their physiological significance is unknown. Here we describe the generation and characterization of brain-specific Idh1 R132H conditional knock-in (KI) mice. mutation results hemorrhage perinatal lethality. Surprisingly, intracellular reactive oxygen species (ROS) are attenuated Idh1-KI brain cells despite an apparent increase NADP + /NADPH ratio. also show high levels D-2-hydroxyglutarate (D2HG) that associated with...
Oxidative stress plays an important role in cancer development and treatment. Recent data implicate the tumor suppressor BRCA1 regulating oxidative stress, but molecular mechanism impact BRCA1-associated tumorigenesis remain unclear. Here, we show that regulates Nrf2-dependent antioxidant signaling by physically interacting with Nrf2 promoting its stability activation. BRCA1-deficient mouse primary mammary epithelial cells low expression of Nrf2-regulated enzymes accumulate reactive oxygen...
Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic undergo migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation plasticity. Lack global metabolic analysis during early cortical development led us explore role cellular metabolism mitochondrial biology ex vivo differentiation primary neurons. Unexpectedly, we observed...