A5049559214- Telomeres, Telomerase, and Senescence
- Drug Transport and Resistance Mechanisms
- Osteoarthritis Treatment and Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Reproductive Biology and Fertility
- Immune cells in cancer
- Sperm and Testicular Function
- Cancer therapeutics and mechanisms
- Cancer-related Molecular Pathways
- Pharmacological Effects and Toxicity Studies
- RNA Interference and Gene Delivery
- Cancer-related molecular mechanisms research
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Advanced biosensing and bioanalysis techniques
- Trace Elements in Health
- Histone Deacetylase Inhibitors Research
- Heparin-Induced Thrombocytopenia and Thrombosis
- Immune Response and Inflammation
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Nanoparticle-Based Drug Delivery
- Venous Thromboembolism Diagnosis and Management
Unity Biotechnology (United States)
2018-2023
Buck Institute for Research on Aging
2010-2015
McGill University
2007-2014
Université de Sherbrooke
2004-2005
Montreal Heart Institute
1992
Cellular senescence is a potent tumor-suppressive mechanism that arrests cell proliferation and has been linked to aging. However, studies of have impeded by the lack simple, exclusive biomarkers senescent state. Senescent cells develop characteristic morphological changes, which include enlarged often irregular nuclei chromatin reorganization. Because alterations nuclear lamina can affect both morphology gene expression, we examined cells. We show here than lamin B1 lost from primary human...
Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question potential function. Here we discover and characterize sets mouse lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds lncRNAs, including 54 several which show exquisitely selective expression in response specific cytokines microbial components a NF-κB-dependent manner. Lethe, lncRNA, is selectively proinflammatory NF-κB or glucocorticoid...
Abstract We elucidated the molecular cross-talk between cartilage and synovium in osteoarthritis, most widespread arthritis world, using powerful tool of single-cell RNA-sequencing. Multiple cell types were identified based on profiling 10,640 synoviocytes 26,192 chondrocytes: 12 distinct synovial 7 articular chondrocyte phenotypes from matched tissues. Intact was enriched for homeostatic hypertrophic chondrocytes, while damaged prefibro- fibro-, regulatory, reparative prehypertrophic...
Immune cells identify and destroy damaged to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report the cell-cycle inhibitor p21 places under immunosurveillance establish a biological timer mechanism controls cell fate. activates retinoblastoma protein (Rb)–dependent transcription at select gene promoters generate complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes chemokine CXCL14, which...
Summary Cellular senescence suppresses cancer by arresting the proliferation of cells at risk for malignant transformation. Recently, senescent were shown to secrete numerous cytokines, growth factors, and proteases that can alter tissue microenvironment may promote age‐related pathology. To identify small molecules suppress senescence‐associated secretory phenotype (SASP), we developed a screening protocol using normal human fibroblasts library compounds are approved use. Among promising...
Summary The selective depletion of senescent cells ( SC s) by small molecules, termed senolytic agents, is a promising therapeutic approach for treating age‐related diseases and chemotherapy‐ radiotherapy‐induced side effects. Piperlongumine PL ) was recently identified as novel agent. However, its mechanism action molecular targets in s unknown thus investigated. Specifically, we used ‐based chemical probe to pull‐down ‐binding proteins from live then mass spectrometry‐based proteomic...
Aging | doi:10.18632/aging.203110. José Alberto López-Domínguez, Sandra Rodríguez-López, Ulises Ahumada-Castro, Pierre-Yves Desprez, Maria Konovalenko, Remi-Martin Laberge, César Cárdenas, Manuel Villalba, Judith Campisi
Transient DNA strand breaks are generated in the whole population of elongating spermatids and perfectly coincident with histone H4 hyperacetylation at chromatin-remodeling steps. Given limited repair capacity spermatids, chromatin remodeling may present a threat to genetic integrity male gamete. The nature breakage, enzymes involved, role process must be determined further investigate potential mutagenic consequences this important transition. We used metachromatic dye acridine orange...
Several causes of male infertility remain idiopathic. Recently, the condensed state sperm head has been demonstrated as a discriminating parameter for assessment infertility. Altered DNA condensation is associated with an increase in strand breakage so genetic integrity gamete threatened. The origin breaks unknown. However, transient appear whole population elongating spermatids during mid-spermiogenesis steps. Most likely, these are required to support change topology chromatin remodeling...
Senescent cells are a major contributor to age-dependent cardiovascular tissue dysfunction, but knowledge of their in vivo cell markers and context is lacking. To reveal tissue-relevant senescence biology, we integrate the transcriptomes 10 experimental models with 224 multi-tissue gene co-expression network based on RNA-seq data seven tissues biopsies from ∼600 coronary artery disease (CAD) patients. We identify 56 senescence-associated modules, many enriched CAD GWAS genes correlated...
There is a growing interest regarding the use of camptothecins (CPTs) for management ovarian cancer. Since topoisomerase I has been established as prime target these drugs in other experimental models, it was important to determine whether sensitivity CPTs cancer cells also correlated with cellular level this enzyme. Despite 7-fold increase expression achieved by adenovirus-mediated expression, CPT derivative (topotecan), not improved compared control harboring an endogenous This observation...