Biology subjects

Elz, A. E.

Publications and source records attributed to Elz, A. E..

4 recordsLinked to original sources

bioRxiv2026

Coordinated expansion of CD163⁺ monocytes and immature CD177⁺ neutrophils marks severe neurotoxicity after CD19 CAR T cell therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a major complication after CAR T cell therapy, but its underlying mechanisms remain poorly understood. We performed longitudinal immune profiling of paired whole blood and serum samples from patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) treated with CD19 CAR T cells. At peak neurotoxicity, high-dimensional mass cytometry and serum proteomics identified the expansion of CD163 monocytes and immature CD10lowCD101low neutrophils correlated with elevated serum ST2 and IL-2RA concentrations. Integrative immune module analysis identified these features among the strongest predictors of ICANS severity. Independent single-cell transcriptomic profiling validated the emergence of immunoregulatory CD163 monocytes and identified CD177 as a biomarker of ICANS-associated immature neutrophils. Together, these findings reveal a coordinated myeloid inflammatory network associated with ICANS and nominate candidate biomarkers and therapeutic targets for improving the safety of CAR T cell therapy. SignificanceWe demonstrate that immunoregulatory CD163+ monocytes and immature, activated CD177hiCD10lowCD101low neutrophils emerge in patients with moderate to severe ICANS at peak toxicity following CD19 CAR T cell therapy. These findings identify an uncharacterized myeloid network potentially contributing towards ICANS pathogenesis.

immunology↗

bioRxiv2025

Evaluating the practical aspects and performance of commercial single-cell RNA sequencing technologies

The rapid development of updated and new commercially available single-cell transcriptomics platforms provides users with a range of experimental options. Cost, sensitivity, throughput, flexibility, and ease of use, all influence the selection of an optimal workflow. We performed a comprehensive comparison of single-cell transcriptomic approaches using multiple standardized PBMCs from different donors. We report on standard single-cell metrics including cell recovery, sequencing efficiency, sensitivity, cell annotation, and differential gene expression for seven recently available kits that interrogate whole transcriptome mRNA, and two that include TCR profiling. We also discuss workflow throughput, sample requirements, timing, cost, and labor as critical factors to consider. In addition to variable experimental constraints imposed by each platform, our findings highlight differences in cell recovery and sensitivity, which we found to significantly influence the ability to resolve cell subtypes. This work provides a basis by which users can balance performance and practical considerations when selecting a single-cell RNA sequencing platform.

genomics↗

bioRxiv2024

Cell Simulation as Cell Segmentation

Single-cell spatial transcriptomics promises a highly detailed view of a cells transcriptional state and microenvironment, yet inaccurate cell segmentation can render this data murky by misattributing large numbers of transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio cell simulation to rapidly infer morphologically plausible cell boundaries that preserve cell type heterogeneity. Benchmarking applied to datasets generated by three commercial platforms show superior performance and computational efficiency of this approach compared with existing methods. We show that improved accuracy in cell segmentation aids greatly in detection of difficult to accurately segment tumor infiltrating immune cells such as neutrophils and T cells. Lastly, through improvements in our ability to delineate subsets of tumor infiltrating T cells, we show that CXCL13-expressing CD8+ T cells tend to be more closely associated with tumor cells than their CXCL13-negative counterparts in data generated from renal cell carcinoma patient samples.

bioinformatics↗

bioRxiv2018

Invasion genetics of the silver carp (Hypophthalmichthys molitrix) across North America: Differentiation of fronts, introgression, and eDNA detection

The invasive silver carp Hypophthalmichthys molitrix escaped from southern U.S. aquaculture during the 1970s to spread throughout the Mississippi River basin and steadily moved northward, now reaching the threshold of the Laurentian Great Lakes. The silver carp is native to eastern Asia and is a large, prolific filter-feeder that decreases food availability for fisheries. The present study evaluates its population genetic variability and differentiation across the introduced range using 10 nuclear DNA microsatellite loci, sequences of two mitochondrial genes (cytochrome b and cytochrome c oxidase subunit 1), and a nuclear gene (ribosomal protein S7 gene intron 1). Populations are analyzed from two invasion fronts threatening the Great Lakes (the Illinois River outside Lake Michigan and the Wabash River, leading into the Maumee River and western Lake Erie), established areas in the southern and central Mississippi River, and a later Missouri River colonization. Results discern considerable genetic diversity and some significant population differentiation, with greater mtDNA haplotype diversity and unique microsatellite alleles characterizing the southern populations. Invasion fronts significantly differ, diverging from the southern Mississippi River population. About 3% of individuals contain a unique and very divergent mtDNA haplotype (primarily the southerly populations and the Wabash River), which may stem from historic introgression in Asia with female largescale silver carp H. harmandi. Nuclear microsatellites and S7 sequences of the introgressed individuals do not significantly differ from silver carp. MtDNA variation is used in a high-throughput sequence assay that identifies and distinguishes invasive carp species and their population haplotypes (including H. molitrix and H. harmandi) at all life stages, in application to environmental (e)DNA water and plankton samples. We discerned silver and bighead carp eDNA from four bait and pond stores in the Great Lakes watershed, indicating that release from retailers comprises another likely vector. Our findings provide key baseline population genetic data for understanding and tracing the invasions progression, facilitating detection, and evaluating future trajectory and adaptive success.

genetics↗