Biology subjects

Skarwan, E.

Publications and source records attributed to Skarwan, E..

3 recordsLinked to original sources

bioRxiv2026

The genetic architecture of dementia risk: how Alzheimer's disease vulnerability converges on lipid metabolism and immune cell networks

Although genome-wide association studies (GWAS) have identified numerous dementia risk loci, their cell-type and tissue-specific contexts remain largely unresolved. We introduced HPA GeneSet Explorer, a statistical pipeline designed to systemically map Genome wide association study (GWAS) disease risk genes across the Human Protein Atlas (HPA). This approach generates a multiscale transcriptomic map of genetic risk, spanning systemic organs, brain regions, and cell types. Applying this framework to Alzheimers disease (AD), Lewy body dementia (DLB), and Frontotemporal dementia (FTD) revealed convergent neuronal enrichment in all three diseases. In addition, we identified AD-specific enrichment in immune system and liver associated gene modules, along with DLB-specific enrichment in ciliary modules. By mapping these vulnerabilities in non-demented samples, we provide a blueprint of the baseline vulnerability hotspots that can precede clinical neurodegeneration, offering new targets for disease-specific therapies and biomarker discovery.

neuroscience↗

bioRxiv2026

A cell type-resolved proteomic atlas of the human body

Proteins define what cells do, yet their systematic quantification across human cell types has remained out of reach. Using Deep Visual Proteomics on tissue from a healthy female donor, we built an atlas of 27 cell types across 14 tissues, quantifying two-thirds of all human protein-coding genes, with up to 8,500 per population. The proteome partitions bimodally into a universal core and highly specialized programs. Integration into the Human Protein Atlas Single Cell Resource enabled comparison of RNA and protein abundance at cell type resolution, revealing that concordance depends on pathway rather than cellular identity. This resolution uncovered cancer-testis antigens in oocytes invisible to bulk profiling. Our openly accessible resource provides a foundation for cell type-resolved proteomics in health and disease.

biochemistry↗

bioRxiv2020

A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress

Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control at the ER.

cell biology↗