A5110941409- Telomeres, Telomerase, and Senescence
- Violence, Religion, and Philosophy
- Augustinian Studies and Theology
- Biblical Studies and Interpretation
- DNA Repair Mechanisms
- Acute Myeloid Leukemia Research
- Political Theology and Sovereignty
- Religion, Society, and Development
- Religion and Society Interactions
- Irish and British Studies
- Skin Protection and Aging
- Philosophical and Historical Studies
- melanin and skin pigmentation
- Religious Education and Schools
- War, Ethics, and Justification
- Advanced biosensing and bioanalysis techniques
- Moravian Church and William Blake
- Immunotherapy and Immune Responses
- Nuclear Structure and Function
- Pneumonia and Respiratory Infections
- Historical, Religious, and Philosophical Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Religious Tourism and Spaces
- Inhalation and Respiratory Drug Delivery
- Medieval Philosophy and Theology
Trinity College Dublin
2018-2025
Queen Mary University of London
2007-2018
University of London
2009-2017
St Bartholomew's Hospital
2016
Heythrop College, University of London
2006-2014
Royal London Hospital
2012
Universidad de Londres
2009
London School of Theology
2009
Zero to Three
2009
Roland Hill (United Kingdom)
2007
Dyskeratosis congenita is a premature aging syndrome characterized by muco-cutaneous features and range of other abnormalities, including early greying, dental loss, osteoporosis, malignancy. cells age prematurely have very short telomeres. Patients mutations in genes that encode components the telomerase complex (dyskerin, TERC, TERT, NOP10), important maintenance Many dyskeratosis patients remain uncharacterized. Here, we describe analysis two proteins, NHP2 GAR1, together with dyskerin...
Dyskeratosis congenita (DC) is characterized by multiple features including mucocutaneous abnormalities, bone marrow failure and an increased predisposition to cancer. It exhibits marked clinical genetic heterogeneity. DKC1 encoding dyskerin, a component of H/ACA small nucleolar ribonucleoprotein (snoRNP) particles mutated in X-linked recessive DC. Telomerase RNA (TERC), the TERT enzymatic telomerase, are autosomal dominant DC, suggesting that DC primarily disease defective telomere...
Dyskeratosis congenita (DC) and its phenotypically severe variant, Hoyeraal-Hreidarsson syndrome (HHS), are multisystem bone-marrow-failure syndromes in which the principal pathology is defective telomere maintenance. The genetic basis of many cases DC HHS remains unknown. Using whole-exome sequencing, we identified biallelic mutations RTEL1, encoding a helicase essential for maintenance regulation homologous recombination, an individual with familial HHS. Additional screening RTEL1 6/23...
Dyskeratosis congenita (DC) is a multisystem bone marrow failure syndrome characterized by triad of mucocutaneous abnormalities and an increased predisposition to malignancy. X-linked DC due mutations in DKC1, while heterozygous TERC (telomerase RNA component) TERT reverse transcriptase) have been found autosomal dominant DC. Many patients with remain uncharacterized, particularly families displaying recessive (AR) inheritance. We now identified novel homozygous 2 unrelated consanguineous...
The primary pathology in many cases of myelodysplasia (MDS) and acute myeloid leukemia (AML) remains unknown. In some cases, two or more affected members have been identified the same family. To date, mutations genes directly implicated: hematopoietic transcription factors RUNX1 (runt-related factor 1) CEBPA (CCATT-box enhancer binding protein α). However, there are also other familial MDS/AML where genetic basis Both MDS, to a lesser extent AML, observed bone marrow failure syndrome...
Dyskeratosis congenita (DC) is an inherited poikiloderma which in addition to the skin abnormalities typically associated with nail dystrophy, leucoplakia, bone marrow failure, cancer predisposition and other features. Approximately 50% of DC patients remain genetically uncharacterized. All genes identified date are important telomere maintenance. To determine genetic basis remaining cases DC, we undertook linkage analysis 20 families a common candidate gene region on chromosome 16 subset...
The bone marrow failure syndrome dyskeratosis congenita (DC) has been considered to be a disorder of telomere maintenance in which disease features arise due accelerated shortening telomeres. By screening core components the telomerase and shelterin complexes patients with DC related syndromes we have identified 24 novel mutations: 11 RNA component (TERC), 8 reverse transcriptase (TERT), 4 dyskerin (DKC1) 1 TRF1-interacting nuclear factor 2 (TINF2). This prompted us review these genetic...
Summary The myelodysplastic syndromes ( MDS ) are heterogeneous and can evolve into acute myeloid leukaemia AML ). Rare familial cases reported in which five disease genes have been identified to date RUNX1 , CEBPA TERC TERT GATA2 Here we report the genetic categorization of 27 families with / . All these were screened for as well TET2 NPM1 Five had telomerase mutations; one a mutation, while none found or mutations. We four heterozygous mutations, each associated different phenotype. While...
<h3>Background</h3> Exposure to cigarette smoke (CS) is associated with increased risk of pneumococcal infection. The mechanism for this association unknown. We recently reported that the particulate matter from urban air simulates platelet-activating factor receptor (PAFR)-dependent adhesion pneumococci airway cells. therefore sought determine whether CS stimulates <h3>Methods</h3> Human alveolar (A549), bronchial (BEAS2-B), and primary epithelial cells (HBEpC) were exposed extract (CSE),...
Significance Bone marrow failure (BMF) is an inherited life-threatening condition characterized by defective hematopoiesis, developmental abnormalities, and predisposition to cancer. BMF caused ERCC6L2 mutations considered be a genome instability syndrome, because DNA repair compromised in patient cells. In this study, we report cases with biallelic disease-causing variants provide evidence from patients’ cells that transcription deficiency can explain the instability. Specifically,...
The article attempts a precise understanding of the concept apocalypse, both in itsbiblical origins, but also its contemporary usage addressing political, economicand environmental crises. An examination New Testament passages, especiallythe ‘little apocalypses’ gospels Mark and Luke, indicate mixture affirmation reticence with regard to apocalyptic mindset. mimetic hypothesis René Girard allows us explain this ambiguity by detecting apocalypticisma temptation Manichaean polarisation against...
Summary Dyskeratosis congenita (DC) is a heterogeneous bone marrow failure disorder with known mutations in components of telomerase and telomere shelterin. Recent work mouse model dyskerin mutation has implicated an increased DNA damage response as part the cellular pathology, while models Terc Tert displayed normal response. To clarify how these contradictory results might apply to DC pathology humans, we studied phenotype primary cells from patients several genetic subtypes, focussing on...
Telomeric dysfunction is linked to colorectal cancer (CRC) initiation. However, the relationship of normal tissue and tumor telomere lengths with CRC progression, molecular features prognosis unclear. Here, we measured relative length (RTL) by real-time quantitative PCR in 90 adenomas (aRTL), 419 stage I-IV CRCs (cRTL) adjacent mucosa (nRTL). Age-adjusted RTL was analyzed against germline variants biology genes, chromosome instability (CIN), microsatellite (MSI), CpG island methylator...
Dyskeratosis congenita (DC) is an inherited multi-system disorder characterised by muco-cutaneous abnormalities, bone marrow failure and a predisposition to malignancy. Bone the principal cause of mortality thought be result premature cell death in haematopoietic compartment because DC cells age prematurely tend have short telomeres. genetically heterogeneous patients mutations genes that encode components telomerase complex (DKC1, TERC, TERT, NOP10 NHP2), telomere shelterin (TINF2), both...
It has been proposed that human telomerase RNA (hTR) interacts with dyskerin, prior to assembly of the holoenzyme. The direct interaction dyskerin and hTR not demonstrated is an experimentally challenging research problem because difficulties in expressing purifying quantities are useful for biophysical analysis. By orthogonally labeling hTR, we have able employ single-molecule two-color coincidence detection (TCCD) observe directly formation a dyskerin.hTR complex. systematic deletion...
The mechanisms by which steatosis renders hepatocytes susceptible to damage in non-alcoholic steatohepatitis (NASH) are unclear although fat accumulation is believed increase hepatocyte susceptibility inflammatory cytokines and oxidative stress. We therefore investigated the of steatotic, hepatocyte-derived cells TNFalpha pro-oxidant, t-butylhydroperoxide (TBH). HepG2 spheroids rendered steatotic fat-loading with 0.15 mM oleic or palmitic acid for 48 h treated TBH 18 exhibited surprisingly...