Biology subjects

Moors, T.

Publications and source records attributed to Moors, T..

3 recordsLinked to original sources

bioRxiv2026

Longitudinal tumor ecosystem mapping defines glioblastoma treatment trajectories

Glioblastoma remains an invariably recurring and lethal brain tumor shaped by complex interactions between malignant and microenvironmental cells. How these interactions evolve under first-line standard-of-care (SOC) therapy remains unclear. We performed spatial single-cell profiling of 671 paired newly diagnosed and recurrent glioblastoma samples from 96 patients to map tumor-ecosystem evolution and its clinical relevance. We delineated five distinct patient subgroups, each characterized by unique ecosystem trajectories that correlated with clinical outcome. Patients whose tumors transitioned into oligodendrocyte-progenitor-like niches with enhanced vascular integrity, oxygenation and an IL10/CCL/MHCII immunomodulatory environment experienced improved clinical prognosis. In contrast, progression towards hypoxic mesenchymal/astrocyte-like niches dominated by strong LGALS1/SPP1/TGF{beta} immunosuppression predicted poor outcome. Furthermore, a subgroup of early-relapsing patients on SOC therapy that was characterized by a depletion of an antigen-presenting myeloid-cell-rich niche, exhibited diminished responsiveness to second-line lomustine therapy. Overall, mapping evolutions in glioblastoma ecosystems offers a novel framework for prognostic stratification and therapeutic guidance.

cancer biology↗

bioRxiv2022

Estimating the prevalence of LAMA2 congenital muscular dystrophy using population genetic databases

BACKGROUNDRecessive pathogenic variants in LAMA2 resulting in complete or partial loss of laminin 2 protein cause congenital muscular dystrophy (LAMA2 CMD). The prevalence of LAMA2 CMD has been estimated by epidemiological studies to lie between 1.36 - 20 cases per million. However, prevalence estimates from epidemiological studies are vulnerable to inaccuracies owing to challenges with studying rare diseases. Population genetic databases offer an alternative method for estimating prevalence. OBJECTIVEWe aim to use population allele frequency data for reported and predicted pathogenic variants to estimate the birth prevalence of LAMA2 CMD. METHODSA list of reported pathogenic LAMA2 variants was compiled from public databases, and supplemented with predicted loss of function (LoF) variants in genome aggregation database (gnomAD). gnomAD allele frequencies for 273 reported pathogenic and predicted LoF LAMA2 variants were used to calculate disease prevalence using a Bayesian methodology. RESULTSThe world-wide birth prevalence of LAMA2 CMD was estimated to be 8.3 per million (95% confidence interval (CI) 6.27 - 10.5 per million). The prevalence estimates for each population in gnomAD varied, ranging from 1.79 per million in East Asians (95% CI 0.63 - 3.36) to 10.1 per million in Europeans (95% CI 6.74 - 13.9). These estimates were generally consistent with those from epidemiological studies, where available. CONCLUSIONSWe provide robust world-wide and population-specific birth prevalence estimates for LAMA2 CMD, including for non-European populations in which LAMA2 CMD prevalence hadnt been studied. This work will inform the design and prioritization of clinical trials for promising LAMA2 CMD treatments.

genetics↗

bioRxiv2017

Lewy pathology in Parkinson’s disease consists of a crowded organellar membranous medley

Parkinsons disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Key neuropathological hallmarks are Lewy bodies and Lewy neurites, which are neuronal inclusions that are immunopositive for the protein -synuclein. In-depth ultrastructural analysis of this Lewy pathology is crucial to understanding pathogenesis and progression of the disease. Using correlative light and electron microscopy/tomography on brain tissue from five Parkinsons disease brain donors, we identified -synuclein immunopositive Lewy pathology and could show that the majority of these features including Lewy bodies and Lewy neurites primarily consists of a crowded membranous medley of vesicular structures and dysmorphic organelles. Only a small fraction of observed Lewy bodies contained predominant proteinaceous filaments, as previously described. The crowding of organellar components was confirmed by STED- based super-resolution microscopy, and high lipid content within the -synuclein immunopositive inclusions was corroborated by confocal imaging, CARS/FTIR imaging and lipidomics. Applying this correlative high-resolution imaging and biophysical approach, we discovered in the postmortem brain of Parkinsons patients a subcellular protein-lipid compartmentalization not previously described in Lewy pathology.

neuroscience↗