ORCID Profile
0000-0001-9951-9395
Current Organisations
UNSW Sydney
,
University of Birmingham
,
University College London
,
Loughborough University
,
German Cancer Research Center (DKFZ)
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Related Links
Publications
Genomic footprints of activated telomere maintenance mechanisms in cancer
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
DOI: 10.1038/S41467-019-13824-9
Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium , we dissect whole-genome sequencing data of over 2500 matched tumor-control s les from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXX trunc ) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor s les contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXX trunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
Author Correction: Genomic footprints of activated telomere maintenance mechanisms in cancer
Publisher: Springer Science and Business Media LLC
Date: 08-12-2022
Pan-cancer analysis of whole genomes
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
DOI: 10.1038/S41586-020-1969-6
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution in acral melanoma, for ex le, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 analyses timings and patterns of tumour evolution 7 describes the erse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 and evaluates a range of more-specialized features of cancer genomes 8,10–18 .
Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures
Publisher: Elsevier BV
Date: 08-2019
Increased vitamin D levels at birth and in early infancy increase offspring allergy risk—evidence for involvement of epigenetic mechanisms
Publisher: Elsevier BV
Date: 02-2016
Views of people living with dementia and their families/care partners: helpful and unhelpful responses to behavioral changes
Publisher: Cambridge University Press (CUP)
Date: 04-11-2022
DOI: 10.1017/S1041610222000849
Abstract: This study investigated the views of people living with dementia and their families/care partners on (i) what they find helpful or unhelpful regarding behavioral changes, i.e. which coping strategies they used for themselves and/or which responses from others, and (ii) what they consider to be appropriate terminology to describe behavioral changes. One-on-one semi-structured interviews were conducted with people living with dementia and families/care partners face to face, online, or over the telephone. Data from open-ended questions were analyzed inductively. Common themes were derived from the data using an iterative approach. Twenty-one people living with dementia and 20 family members/care partners were interviewed. Four main themes were derived for helpful responses, and three main themes for unhelpful responses. Helpful responses included providing clear professional support pathways and supportive environments where people living with dementia can engage in physical, cognitive, social, and spiritual activities. Unhelpful responses included discriminatory treatment from others and use of medicalized terminology. Views toward terminology varied people with lived experience most favored using “changed behaviors” over other terminology. Areas for improvement included targeting dementia stigma, societal education on dementia, and building confidence in people living with dementia by focusing on living well with dementia. Knowledge of the views of people living with dementia may assist healthcare professionals to provide more appropriate care for people living with dementia.
Pharmacological and nonpharmacological approaches to reduce disinhibited behaviors in dementia: a systematic review
Publisher: Cambridge University Press (CUP)
Date: 25-03-2022
DOI: 10.1017/S1041610222000151
Abstract: Disinhibited behaviors in dementia are associated with multiple negative outcomes. However, effective interventions are under-researched. This systematic review aims to provide an overview of intervention studies that report outcome measures of disinhibited behaviors in dementia. Systematic searches of the databases MEDLINE, EMBASE, and PsychINFO, Social Work Abstracts and Cochrane Central Register of Controlled Trial databases were conducted for publications published between 2002 and March 2020. We included hand-searched reviews, original articles, case reports, cohort studies, and randomized controlled trials (RCTs). All studies were rated for research quality. Statistical and clinical significance were considered for in idual studies. Effect sizes were included where provided or calculated where possible. Mean effect sizes were calculated for RCTs only. The systematic review included studies involving people living with dementia. The Neuropsychiatric Inventory disinhibition subscale was used most often. Nine pharmacological and 21 nonpharmacological intervention studies utilized different theoretical/clinical approaches. These included pain management, antidepressants, models of care, education and/or training, music-based approaches, and physical activity. The quality of research in RCTs was strong with a greater effect size in nonpharmacological compared to pharmacological approaches (mean Cohen’s d = 0.49 and 0.27, respectively). Disinhibition was a secondary outcome in all studies. Pharmacological (including pain management and antidepressants) and, more so, nonpharmacological (models of care, education/training, physical activity, and music) approaches were effective in reducing disinhibition.
Shear-sensitive nanocapsule drug release for site-specific inhibition of occlusive thrombus formation
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1111/JTH.13666
Abstract: Essentials Vessel stenosis due to large thrombus formation increases local shear 1-2 orders of magnitude. High shear at stenotic sites was exploited to trigger eptifibatide release from nanocapsules. Local delivery of eptifibatide prevented vessel occlusion without increased tail bleeding times. Local nanocapsule delivery of eptifibatide may be safer than systemic antiplatelet therapies. Background Myocardial infarction and stroke remain the leading causes of mortality and morbidity. The major limitation of current antiplatelet therapy is that the effective concentrations are limited because of bleeding complications. Targeted delivery of antiplatelet drug to sites of thrombosis would overcome these limitations. Objectives Here, we have exploited a key biomechanical feature specific to thrombosis, i.e. significantly increased blood shear stress resulting from a reduction in the lumen of the vessel, to achieve site-directed delivery of the clinically used antiplatelet agent eptifibatide by using shear-sensitive phosphatidylcholine (PC)-based nanocapsules. Methods PC-based nanocapsules (2.8 × 10
Related Organisations
University Of Oxford
Location: United Kingdom of Great Britain and Northern Ireland
University Of Birmingham
Location: United Kingdom of Great Britain and Northern Ireland
University College London
Location: United Kingdom of Great Britain and Northern Ireland
Loughborough University
Location: United Kingdom of Great Britain and Northern Ireland
Oxford Health NHS Foundation Trust
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Karsten Rippe.