A5101547087- Telomeres, Telomerase, and Senescence
- Immune cells in cancer
- Genomics and Chromatin Dynamics
- Cell Adhesion Molecules Research
- Single-cell and spatial transcriptomics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immunotherapy and Immune Responses
- Retinoids in leukemia and cellular processes
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Ear and Head Tumors
- Autophagy in Disease and Therapy
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Hypothalamic control of reproductive hormones
- Acute Lymphoblastic Leukemia research
- Reproductive biology and impacts on aquatic species
- Circadian rhythm and melatonin
- Nanoplatforms for cancer theranostics
- Genomics and Phylogenetic Studies
- Plant Molecular Biology Research
- Childhood Cancer Survivors' Quality of Life
Cancer Research UK Cambridge Center
2022-2024
University of Cambridge
2019-2024
Cancer Research UK
2019-2024
University of Malaya
2014-2017
University College London
2014
University Malaya Medical Centre
2014
University of Michigan
1997
University of Minnesota
1995
University of Toronto
1972
Senescent cells trigger their own immune-mediated destruction, termed senescence surveillance. This is dependent on the inflammatory senescence-associated secretory phenotype (SASP), which includes COX2, an enzyme with complex roles in cancer. The role COX2 plays during surveillance unknown. Here, we show that RAS-induced (RIS), a critical regulator of SASP composition and vivo. regulates expression multiple components through autocrine feedback loop involving its downstream product,...
Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than their peers. The authors investigated whether young adult survivors acute lymphoblastic leukemia (ALL) a biologic phenotype cellular ageing chronic inflammation.Plasma inflammatory cytokines were measured using cytometric bead array 87 asymptomatic ALL (median age, 25 years; age range, 18-35 years)...
Senescence is a state of stable proliferative arrest, generally accompanied by the senescence-associated secretory phenotype, which modulates tissue homeostasis. Enhancer-promoter interactions, facilitated chromatin loops, play key role in gene regulation but their relevance senescence remains elusive. Here, we use Hi-C to show that oncogenic RAS-induced human diploid fibroblasts extensive enhancer-promoter rewiring, closely connected with dynamic cohesin binding genome. We find de novo...
Senescence is a stress-responsive tumor suppressor mechanism associated with expression of the senescence-associated secretory phenotype (SASP). Through SASP, senescent cells trigger their own immune-mediated elimination, which if evaded leads to tumorigenesis. Senescent parenchymal are separated from circulating immunocytes by endothelium, targeted microenvironmental signaling. Here we show that SASP induces endothelial cell NF-κB activity and SASP-induced canonical component
The rapid and reversible upregulation of the functional activity integrin receptors on T lymphocytes is a vital step in adhesive interactions that occur during successful cell recognition foreign antigen transendothelial migration. Although ligation several different surface receptors, including antigen-specific CD3/T receptor complex, CD2, CD7, CD28 antigens, as well chemokine has been shown to rapidly upregulate function, intracellular signaling events initiate this increase adhesion...
Abstract Oncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with premalignancy 1,2 . Achieving this phenotype typically requires a high level of oncogenic stress, yet the provoked by lower dosage remains unclear. Here we develop RAS dose-escalation models in vitro and vivo, revealing dose-driven non-linear continuum downstream phenotypes. In hepatocyte OIS model ectopic expression NRAS(G12V) does not induce tumours, part owing to OIS-driven immune...
Significance Germ-line mutation in the tumor suppressor TP53 causes Li–Fraumeni syndrome (LFS), a complex predisposition to multiple cancers. Types of cancers and ages at diagnosis vary among subjects families, with apparent genetic anticipation: i.e., earlier cancer onset successive generations. It has been proposed that anticipation is caused by accumulation copy-number variations (CNV) context haploinsufficiency. Using genome/exome sequencing, we found no evidence increased rates CNVs two...
The functional activity of integrin receptors on T cells is dynamically regulated so that can alternate rapidly between adhesive and nonadhesive states. CD7 Ag one several molecules transduce intracellular signals up-regulate integrin-mediated adhesion. We demonstrate in this report the signaling pathway utilizes to regulate involves lipid kinase phosphatidylinositol 3-kinase (PI 3-K). stimulation both Jurkat resting human peripheral blood CD4+ results rapid association activation PI 3-K...
Scientific advances build on the findings of existing research. The 2001 publication human genome has led to production huge volumes literature exploring context-specific functions and interactions genes. Technology is needed perform large-scale text mining research papers extract reported actions genes in specific experimental contexts cell states, such as cancer, thereby facilitating design new therapeutic strategies.
Type of cancer and age onset in individuals with inherited aberrations the tumour suppressor gene TP53 are variable, possibly influenced by genetic modifiers different environmental exposure. Since 2009, modified Chompret criteria (MCC) have been used to identify for mutation screening. Using database maintained International Agency Research on Cancer (IARC), we investigated if MCC, mainly developed a Caucasian population, was also applicable Asia. We identified several differences Asian...
Although the ultimobranchial gland of chick has been shown to contain large amounts calcitonin relatively few reports have published on its fine structure. In present study, ultrastructure gland, with emphasis cells which appear be producers hormone, will examined. Ultimobranchial glands were obtained from twenty 2-week-old chicks and fixed in glutaraldehyde followed by osmium tetroxide. The is composed aggregate cords clusters interspersed variable numbers cyst-like cavities. Two...
Abstract In classical Oncogene Induced Senescence (OIS) model, cells secrete a milieu of signaling molecules referred to as the senescence-associated secretory phenotype (SASP). This SASP attracts immune effector proximity senescent undertake elimination, thus impeding their potential progression into fully fledged malignancy1. Achieving such clearance typically requires high level oncogenic stress, yet provoked by lower dosage remains unclear. Recently, we developed RAS-dose escalation...
Abstract In classical Oncogene Induced Senescence (OIS) model, cells secrete a milieu of signaling molecules referred to as the senescence-associated secretory phenotype (SASP). This SASP attracts immune effector proximity senescent undertake elimination, thus impeding their potential progression into fully fledged malignancy1. Achieving such clearance typically requires high level oncogenic stress, yet provoked by lower dosage remains unclear. Recently, we developed RAS-dose escalation...
Abstract Senescence is a phenotypic state of stable proliferative arrest, typically occurring in lineage-committed cells and triggered by various stimuli. It generally accompanied activation secretory program (senescence-associated phenotype, SASP), which modulates both local (tissue microenvironment) systemic (ageing) homeostasis 1,2 . Enhancer-promoter interactions play key role gene regulation 3–5 , facilitated chromatin loops, mostly formed via CCCTC binding factor (CTCF) cohesin...
Abstract Autophagy has been implicated in male fertility but its specific role the post-testicular organs remains unclear. Here, we investigate this mice expressing a doxycycline-inducible RNAi against Atg5 (Atg5i). Systemic autophagy inhibition Atg5i resulted morphological and functional abrogation of accessory sex organs, leading to subfertility. However, testis was largely protected, likely due limited permeability doxycycline through blood-testis barrier. Interestingly, restoration by...
<title>Abstract</title> Oncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with pre-malignancy<sup>1-3</sup>. Achieving this phenotype typically requires a high level of oncogenic stress, yet the provoked by lower dosage remains unclear. Here we develop RAS-dose escalation models in vitro and vivo, revealing RAS-dose-driven non-linear continuum downstream phenotypes. In hepatocyte OIS model where ectopic expression NRAS<sup>G12V</sup> fails to...
Abstract Cellular senescence is a fate-determined state, accompanied by reorganization of heterochromatin. While lineage-appropriate genes can be temporarily repressed through facultative heterochromatin, stable silencing lineage-inappropriate often involves the constitutive heterochromatic mark, histone H3K9me3. The fate these during chromatin accompanying unclear. Here we show small number are derepressed in senescent cells from H3K9me3 regions that gain open marks. DNA FISH experiments...