A5076786884- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Bioinformatics and Genomic Networks
- Pluripotent Stem Cells Research
- Genetic Associations and Epidemiology
- Schizophrenia research and treatment
- Neurogenesis and neuroplasticity mechanisms
- Computational Drug Discovery Methods
- Machine Learning in Bioinformatics
- Genomics and Chromatin Dynamics
- Global Maternal and Child Health
- Pharmaceutical Practices and Patient Outcomes
- Advanced Proteomics Techniques and Applications
- Advanced Neuroimaging Techniques and Applications
- Immune cells in cancer
- Vaccine Coverage and Hesitancy
- Genetics and Neurodevelopmental Disorders
- Digital Mental Health Interventions
- GDF15 and Related Biomarkers
- Ion Transport and Channel Regulation
- Education Methods and Practices
- Metabolomics and Mass Spectrometry Studies
- Functional Brain Connectivity Studies
- Circular RNAs in diseases
- Iron Metabolism and Disorders
Emory University
2024
King's College London
2010-2017
South London and Maudsley NHS Foundation Trust
2012-2017
National Institute for Health Research
2017
Centre for Mental Health
2012-2016
National Health Service
2012-2014
University of Essex
2007
Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural activate neurogenesis--and, particular, the that they regulate--however, mostly unknown. We performed a genome-wide characterization of transcriptional targets embryonic brain stem cultures location analysis expression profiling embryos overexpressing or mutant for Ascl1. wide range molecular cellular functions...
Abstract Blood proteins and their complexes have become the focus of a great deal interest in context potential as biomarkers Alzheimer's disease (AD). We used SOMAscan assay for quantifying 1001 blood samples from 331 AD, 211 controls, 149 mild cognitive impaired (MCI) subjects. The strongest associations protein levels with AD outcomes were prostate‐specific antigen complexed to α1‐antichymotrypsin (AD diagnosis), pancreatic prohormone diagnosis, left entorhinal cortex atrophy, hippocampus...
The CATH database of protein domain structures ( http://www.biochem.ucl.ac.uk/bsm/cath/ ) currently contains 43 229 domains classified into 1467 superfamilies and 5107 sequence families. Each structural family is expanded with relatives from GenBank completed genomes, using a variety efficient search protocols reliable thresholds. This extended 616 470 sequences 23 876 results in the significant expansion HMM model library to include models built relatives, giving 10% increase coverage for...
The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how interacts with chromatin landscape regulate when promoting differentiation. We find that binding occurs mostly at distal enhancers is associated activation transcription. Surprisingly, accessibility its sites neural stem/progenitor cells remains largely unchanged throughout...
Objectives To identify negative symptoms in the clinical records of a large sample patients with schizophrenia using natural language processing and assess their relationship outcomes. Design Observational study an anonymised electronic health record case register. Setting South London Maudsley NHS Trust (SLaM), provider inpatient community mental healthcare UK. Participants 7678 receiving care during 2011. Main outcome measures Hospital admission, readmission duration admission. Results 10...
Changes in brain amyloid burden have been shown to relate Alzheimer's disease pathology, and are believed precede the development of cognitive decline. There is thus a need for inexpensive non-invasive screening methods that able accurately estimate as marker disease. One potential method would involve using demographic information measurements on plasma samples establish biomarkers burden; this study data from Disease Neuroimaging Initiative was used explore possibility. Sixteen analytes...
A marker of Alzheimer's disease (AD) that can accurately diagnose at the earliest stage would significantly support efforts to develop treatments for early intervention. We have sought determine sensitivity and specificity periphera
Objectives Electronic healthcare records (EHRs) are a rich source of information, with huge potential for secondary research use. The aim this study was to develop an application identify instances Adverse Drug Events (ADEs) from free text psychiatric EHRs. Methods We used the GATE Natural Language Processing (NLP) software mine ADEs content within Clinical Record Interactive Search (CRIS) system, de-identified case register developed at South London and Maudsley NHS Foundation Trust, UK....
Abstract Huntingtin (Htt) protein interacts with many transcriptional regulators, widespread disruption to the transcriptome in Huntington's disease ( HD ) brought about by altered interactions mutant Htt (muHtt) protein. Repressor Element‐1 Silencing Transcription Factor REST is a repressor whose association cytoplasm disrupted , leading increased nuclear and concomitant repression of several neuronal‐specific genes, including brain‐derived neurotrophic factor Bdnf ). Here, we explored wide...
Background: Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer’s disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of prove more robust. Objectives: This study aimed investigate whether a case/control classification model built on pathway level data was robust than consequently perform better...
Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, 'reactive' offer an alternative source of for central nervous system (CNS) repair injury or disease. At present, mechanisms regulate potential different types poorly understood....
Background Modeling trajectories of decline can help describe the variability in progression cognitive impairment dementia. Better characterisation these has significant implications for understanding disease progression, trial design and care planning. Methods Patients with at least three Mini-mental State Examination (MMSE) scores recorded South London Maudsley NHS Foundation Trust Electronic Health Records, UK were selected (N = 3441) to form a retrospective cohort. Trajectories...
Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression the pluripotency regulatory program and reciprocal activation neurogenic program. Upon neural induction, ESCs rapidly repress expression genes followed by staged progenitor differentiated neuronal glial genes. The transcriptional factors that underlie maintenance are partially characterized whereas those underlying induction much less explored, coordinate these two developmental programs completely unknown....
Background:The search for a biomarker of Alzheimer's disease (AD) pathology (amyloid- (A) and tau) is ongoing, with the best markers currently being measurements A tau in cerebrospinal fluid (CSF) via positron emission tomography (PET) scanning.These methods are relatively invasive, costly, often have high screening failure rates.Consequently, research aiming to elucidate blood biomarkers tau.Objective: This study aims investigate case/control polygenic risk score (PGRS) as marker...
Affymetrix GeneChips are a popular platform for performing whole-genome experiments on the transcriptome. There range of different calibration steps, and users presented with choices background subtractions, normalisations expression measures. We wished to establish which steps resulted in biggest uncertainty sets genes reported be differentially expressed. Our results indicate that identified as being most significantly expressed, estimated by z-score fold change, is relatively insensitive...
A patient with a history of schizophrenia was brought to the emergency department extensive self-inflicted soft tissue injuries. Primary polydipsia evident on admission, because he had maximally dilute urine, urine flow rate 10 ml/min, and hyponatraemia (100 mmol/l). During an imaginary consultation Professor McCance in which applied basic principles integrative physiology deductive analysis quantitative terms, other reasons for polyuric state were considered. Moreover, based very low value...
Abstract NOTE The biases seen in simulations of Temporal Clustering appear to be even worse real applications. While this was a novel and interesting approach, ultimately work has been discontinued. I feel the are due propagated error estimating individual level offsets based on single noisy measure, amplified by fact that high MMSE scores change very slowly therefore many estimates from near an asymptote left hand model. We continue area, with other approaches showing significantly more...
It is challenging to study long-term progression of Alzheimer’s disease due short-term follow-up individuals and heterogeneity. Progression can be heterogeneous in itself, but additionally begin studies at different ages, times relative onset. Here we propose the first method – Temporal Clustering that jointly tackle these sources heterogeneity produce models progression. Data used preparation this article was obtained from PAQUID (data extracted R package lcmm), Disease Neuroimaging...
Background: There is an urgent need to discover Alzheimer’s disease (AD) biomarkers that are both easily measured and reliable. Research into blood-based for AD using transcriptomics proteomics has been attractive promising area of research. However, date researchers have not looked the possibility medication being a confounding factor in these studies. Objective: This study explored whether acetylcholinesterase inhibitors (AChEIs), main class medication, blood biomarker Methods: The most...
A better understanding of the biological mechanisms underlying Alzheimer's Disease (AD) is required. Studies have now demonstrated promise using associations with blood metabolites, as functional intermediate phenotypes in biomedical and pharmaceutical research1. further identified genetic variants metabolism-related genes that lead to clearly differentiated metabolic phenotypes, ‘genetically influenced metabotypes’ (GIMs), providing new insights role inherited variation diversity2....