Biology subjects

Weiss, C. A.

Publications and source records attributed to Weiss, C. A..

3 recordsLinked to original sources

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↗

bioRxiv2025

Single cell spatial proteomics maps human liver zonation patterns and their vulnerability to fibrosis

Understanding protein distribution patterns across tissue architecture is crucial for deciphering organ function in health and disease. Here, we applied single-cell Deep Visual Proteomics to perform spatially-resolved proteome analysis of individual cells in native tissue. We combined this with a novel strategic cell selection pipeline and a continuous protein gradient mapping framework to investigate larger clinical cohorts. We generated a comprehensive spatial map of the human hepatic proteome by analyzing hundreds of individual hepatocytes from 18 individuals. Among more than 2,500 proteins per cell about half exhibited zonated expression patterns. Cross-species comparison with mouse data revealed conserved metabolic functions and human-specific features of liver zonation. Analysis of fibrotic samples demonstrated widespread disruption of protein zonation, with pericentral proteins being particularly susceptible. Our study provides a comprehensive resource of human liver organization while establishing a broadly applicable framework for spatial proteomics analyses along tissue gradients.

molecular biology↗

bioRxiv2019

Oligoribonuclease functions as a diribonucleotidase to bypass a key bottleneck in RNA degradation

Degradation of RNA polymers is a multistep process catalyzed by specific subsets of RNases. In all cases, degradation is completed by exoribonucleases that recycle RNA fragments into nucleotide monophosphate. In {gamma}-proteobacteria, a group of up to eight 3-5 exoribonucleases have been implicated in RNA degradation. Oligoribonuclease (Orn) is unique among them as its activity is required for clearing short RNA fragments, a function important for cellular fitness. However, the mechanistic basis for this substrate selectivity remained unclear. Here we show that Orns activity as a general exoribonuclease has been vastly overestimated by demonstrating that the enzyme exhibits a much narrower substrate preference for diribonucleotides. Co-crystal structures of Orn with substrates reveal an active site optimized for diribonucleotides that does not accommodate longer substrates. While other cellular RNases process oligoribonucleotides down to diribonucleotide entities, our functional studies demonstrate that Orn is the one and only diribonucleotidase that completes the final stage of the RNA degradation pathway. Together, these results indicate that Orn is a dedicated diribonucleotidase that clears the diribonucleotide pool that otherwise affects cellular physiology and viability.

microbiology↗