Biology subjects

Ariss, M.

Publications and source records attributed to Ariss, M..

4 recordsLinked to original sources

bioRxiv2026

Brain shuttle target expression levels vary by individual, not by brain region, disease, age, or sex

Therapeutics fused to brain shuttles that exploit endogenous receptor-mediated transport at the blood-brain barrier (BBB) offer a promising strategy to deliver large molecule drugs and biologics to the CNS. A fundamental but untested assumption underlying their clinical development is that their endothelial receptor targets are consistently expressed between individuals and between patient populations. Here, we analyzed gene and protein expression of eleven canonical brain shuttle targets in isolated human brain microvascular endothelial cells and brain microvessels from 11 large cohorts, using single-cell and single-nucleus transcriptomics and quantitative proteomics. Expression was remarkably stable between brain regions, sexes, ages, and normal health versus four major neurodegenerative conditions, Alzheimers disease, Parkinsons disease, Huntingtons disease, and amyotrophic lateral sclerosis, with 612 of 631 comparisons (97%) showing no significant difference. Regional heterogeneity of brain shuttle targets previously reported in rodent models was not observed in human tissue, and disease states had minimal impact in all diseases examined. In striking contrast, target abundance differed consistently among individuals in every demographic and clinical group, for all eleven targets and all data modalities. These findings establish individual receptor abundance as a critical and previously uncharacterized variable for brain shuttle translational research, including clinical trial design and patient stratification.

neuroscience↗

bioRxiv2025

Cell signaling pathways discovery from multi-modal data

Deciphering cell signaling pathways is key to understanding biology, disease mechanisms, and developing new therapies. Although advances in multi-omics technologies provide richer insight into signaling, the data remain high-dimensional, heterogeneous, and difficult to interpret, and current computational tools for inferring signaling pathways are limited. To address this, we developed Incytr, a method for efficient discovery of cell signaling pathways through integration of diverse data modalities, including transcriptomics, ATAC-seq, proteomics, phosphoproteomics, and kinomics. We demonstrate its application in COVID-19, Alzheimers disease, and cancer, where it successfully recovers known pathways and generates novel, cell-type-specific hypotheses supported by multiple data types. We further show how integrating Incytr-derived pathways with biomarker and drug databases can support target and drug discovery. Finally, we show that using Incytr-derived signaling pathways as training data for simple natural language processing models can deepen our understanding of cell-cell communication and immune cell dynamics, while helping identify new therapeutic targets.

bioinformatics↗

bioRxiv2024

CESA: Cross-species Epitope Sequence Analysis for discovery of existing antibodies useful for phospho-specific protein detection in model species

Signaling pathways play key roles in many important biological processes such as cell division, differentiation, and migration. Phosphorylation site-specific antibodies specifically target proteins phosphorylated on a given tyrosine, threonine, or serine residue. Use of phospho-specific antibodies facilitates analysis of signaling pathway regulation and activity. Given the usefulness of phospho-specific antibodies, a number of collections of these antibodies have been generated, typically for detection of phosphorylated mammalian proteins. Anecdotal evidence shows that some of these are also useful for detection of phosphorylated forms of orthologous proteins in model organisms. We propose that anti-phospho-mammalian protein antibody collections comprise an untapped resource for research in other species. To systematically analyze the potential utility of anti-phospho-mammalian protein antibodies in other species, we developed the Cross-species Epitope Sequence Analysis software tool (CESA). CESA identifies and aligns orthologous proteins in model species, then analyzes conservation of antibody target sites. We used CESA to predict what phospho-specific antibodies in a collection from Cell Signaling Technology (CST) might be useful for studies in Drosophila melanogaster and other species. CESA predicts that more than 232 sites on 116 Drosophila proteins can potentially be targeted by the antibodies initially developed at CST to detect human, mouse, or rat phosphoproteins.

bioinformatics↗

bioRxiv2019

A single-cell transcriptome atlas of the adult muscle precursors uncovers early events in fiber-type divergence in Drosophila

In Drosophila, the wing disc-associated adult muscle precursors (AMPs) give rise to the fibrillar indirect flight muscles (IFM) and the tubular direct flight muscles (DFM). To understand early transcriptional events underlying this muscle diversification, we performed single cell RNA-sequencing experiments and built a cell atlas of AMPs associated with third instar larval wing disc. Our analysis identified distinct transcriptional signatures for IFM and DFM precursors that underlie the molecular basis of their divergence. The atlas further revealed various states of differentiation of AMPs, thus illustrating previously unappreciated spatial and temporal heterogeneity among them. We identified and validated novel markers for both IFM and DFM precursors at various states of differentiation by immunofluorescence and genetic tracing experiments. Finally, we performed a systematic genetic screen using a panel of markers from the reference cell atlas as an entry point and found a novel gene, Ama, which is functionally important in muscle development. Thus, our work provides a framework of leveraging scRNA-seq for gene discovery and therefore, this strategy can be applied to other scRNA-seq datasets.

genetics↗