Biology subjects

Clapp, W.

Publications and source records attributed to Clapp, W..

3 recordsLinked to original sources

bioRxiv2024

ComPRePS: An Automated Cloud-based Image Analysis tool to democratize AI in Digital Pathology

Digital pathology using whole slide imaging (WSI) and artificial intelligence (AI) has the potential to transform diagnostic workflows, but adoption remains limited by technical complexity and scalability. We developed the Computational Renal Pathology Suite (ComPRePS), a scalable cloud-based platform that automates WSI ingestion, compartmental segmentation, feature extraction, and AI-assisted interpretation through an integrated high-performance architecture. ComPRePS was evaluated in two use cases. First, using 213 procurement biopsies, we compared conventional assessments with automated AI analyses and a hybrid AI-assisted expert workflow. ComPRePS AI-assisted methods achieved higher precision and significantly improved interobserver agreement for key lesions, including global glomerulosclerosis, interstitial fibrosis and tubular atrophy, and arterial intimal thickening. Second, ComPRePS enabled high-throughput quantitative profiling of glomerular and tubular features across minimal change disease, diabetic nephropathy, and amyloid nephropathy revealing disease-specific phenotypic patterns inaccessible to manual evaluation. Overall, ComPRePS improves reproducibility, interpretability, and objectivity in renal pathology, bridging computation with clinical practice.

pathology↗

bioRxiv2024

Spatial Transcriptomics of Spinal Ependymoma in NF2-related Schwannomatosis

Spinal ependymoma (SP-EPN) is a central nervous system (CNS) tumor that is associated with high morbidity. The only effective treatment for end-stage SP-EPN is surgery, but this is associated with high risk of injury to the sensorimotor spinal tracts and paralysis. There is a critical need to understand the cellular origins of this tumor so that disease models of tumor progression can be generated for drug development. Recent genomic studies with bulkRNA sequencing suggest the molecular signature of SP-EPN matches that of ependymal cells (EPCs). However, large-scale genomic studies can often misrepresent rare cancer stem cell populations within the tumor. In this study, we performed spatial transcriptomics (ST) on a SP-EPN resected from a patient with NF2-related neurofibromatosis to examine the spatial heterogeneity within the tumor. The SP-EPN sample exhibited cellular heterogeneity with diffuse expression of astrocytic and EPC markers, and smaller pockets with RGC or stem cell markers, as well as overlap between progenitor cell and mature cell markers. These findings suggest that there may be a developmental hierarchy within the EPC lineage in SP-EPN tumors, which may stem from aberrant radial glia cells.

cancer biology↗

bioRxiv2022

Kidney tubular epithelial cell ferroptosis links glomerular injury to tubulointerstitial pathology in lupus nephritis

ObjectiveAn appreciation of factors that lead to tubular injury in lupus nephritis is lacking. Iron accumulates in the kidney tubules of nephritic patients and lupus-prone nephritic mice. Ferroptosis is a druggable, iron-dependent form of cell death that has received little attention in lupus nephritis. This study investigated whether intra-renal ferroptosis is a target for intervention in lupus nephritis. MethodsKidneys of lupus nephritis patients and two spontaneous murine models of lupus nephritis were characterized for ferroptosis using protein, RNA, and lipidomics-based approaches. Susceptibility of heavy chain ferritin (FtH1; an essential iron sequestration protein) deficient proximal tubular epithelial cells (PTECs) was studied using nephrotoxic serum nephritis and FtH1 knockdown human PTECs. The benefit of Liproxstatin-2, a novel second-generation ferroptosis, was evaluated using human PTECs exposed to lupus nephritis patients serum. ResultsHuman and murine nephritic kidneys have the characteristic markers of ferroptosis, such as 4-hydroxynonenal and acyl-CoA synthetase long-chain family member 4, mainly in the tubular segments. Murine kidneys showed impairment in the glutathione synthesis pathway, decreased expression of glutathione peroxidase 4, a glutathione-dependent ferroptosis inhibitor, and characteristic ferroptotic lipid signature. Loss of FtH1 increased PTEC pathology independent of glomerular injury. These findings were recapitulated in human PTECs. Of translational relevance, Liproxstatin-2 demonstrated a prophylactic and therapeutic benefit in mitigating lupus nephritis patient serum-induced PTEC ferroptosis. ConclusionOur findings highlight tubular cell ferroptosis as a pathological feature in human and murine lupus nephritis and identify ferroptosis inhibitors as potential novel adjunct therapeutics to treat lupus nephritis.

immunology↗