Biology subjects

Stauffer, W.

Publications and source records attributed to Stauffer, W..

3 recordsLinked to original sources

bioRxiv2025

Biomarker Quantification in Breast Cancer using Xenium In Situ

Advances in spatial transcriptomics enable high-throughput quantitation of both established and novel biomarkers at single cell resolution, offering the potential to transform diagnostics. Using Xenium in situ technology in FFPE human breast samples, we address two challenges in the cancer field: 1. achieving reliable normalization of gene expression across heterogeneous sample populations; 2. identifying biomarkers that predict invasion or metastasis. We describe a scalable approach to identify low-variation housekeeping (HK) genes within any given sample set, then use those HK genes for cross- and intra-sample normalization of biomarkers. Analyzing 12 FFPE human breast samples-primarily ductal carcinoma in situ (DCIS)-with a custom 280-gene panel, we identified four HK genes (EEF1G, EEF2, MALAT1, and RPLP0) that exhibited minimal variability in tumor cells, four tumor cell biomarkers (LDHA, SDC1, PIGR, SFRP1) that increased or decreased with tumor grade, and one tumor-associated myoepithelial biomarker (LAMC2). Normalizing biomarkers to the four HK genes preserved the dynamic range of expression necessary for distinguishing tumor grades, outperforming HKs from legacy RT-PCR diagnostic panels. Lastly, we employed a cell-agnostic approach in the tumor periphery to quantify MMP11, a biomarker correlated with proliferative and potentially pre-invasive ducts. Our results establish a single cell normalization method for spatial in situ transcriptomics and reveal and quantitate biomarkers relevant to DCIS risk and progression.

cancer biology↗

bioRxiv2023

The Cyclophilin Inhibitor Rencofilstat Decreases HCV-induced Hepatocellular Carcinoma Independently of Its Antiviral Activity

There is an urgent need for the identification of new drugs that inhibit HCV-induced hepatocellular carcinoma (HCC). Our work demonstrates that cyclophilin inhibitors (CypI) represent such new drugs. We demonstrated that the non-immunosuppressive cyclosporine A (CsA) analog (CsAa) rencofilstat possesses dual therapeutic activities for the treatment of HCV infection and HCV-induced HCC. Specifically, we showed that HCV infection of humanized mice results in the progressive development of HCC. This was true for four genotypes tested (1 to 4). Remarkably, we demonstrated that rencofilstat inhibits the development of HCV-induced HCC in mice even when added 16 weeks post-infection when HCC is well established. Importantly, we showed that rencofilstat drastically reduces HCC progression independently of its anti-HCV activity. Indeed, the CypI rencofilstat inhibits HCC while other anti-HCV agents such as NS5A (NS5Ai) and NS5B (NS5Bi) fail to reduce HCC. In conclusion, this study shows for the first time that the CypI rencofilstat represents a potent therapeutic agent for the treatment of HCV-induced HCC.

microbiology↗

bioRxiv2021

Crossover patterning through kinase-regulated condensation and coarsening of recombination nodules

Meiotic recombination is highly regulated to ensure precise segregation of homologous chromosomes. Evidence from diverse organisms indicates that the synaptonemal complex (SC), which assembles between paired chromosomes, plays essential roles in crossover formation and patterning. Several additional "pro-crossover" proteins are also required for recombination intermediates to become crossovers. These typically form multiple foci or recombination nodules along SCs, and later accumulate at fewer, widely spaced sites. Here we report that in C. elegans CDK-2 is required to stabilize all crossover intermediates and stabilizes interactions among pro-crossover factors by phosphorylating MSH-5. Additionally, we show that the conserved RING domain proteins ZHP-3/4 diffuse along the SC and remain dynamic following their accumulation at recombination sites. Based on these and previous findings we propose a model in which recombination nodules arise through spatially restricted biomolecular condensation and then undergo a regulated coarsening process, resulting in crossover interference.

cell biology↗