Biology subjects

Pavel, A. B.

Publications and source records attributed to Pavel, A. B..

3 recordsLinked to original sources

bioRxiv2021

Th1, Th2 and Th17 inflammatory pathways synergistically correlate with cardiometabolic processes. A case study in COVID-19.

A predominant source of complication in SARS-CoV-2 patients arises from the cytokine storm, an elevated expression of inflammatory helper T-cell associated cytokines that can lead to tissue damage and organ failure. The high inflammatory burden of this viral infection often results in cardiovascular comorbidities. A better understanding of the interaction between the cytokine storm and cardiovascular proteins might inform medical decisions and therapeutic approaches. We hypothesized that all major helper T-cell inflammatory pathways (Th1, Th2 and Th17) synergistically contribute to cardiometabolic modifications in serum of COVID-19 patients. We proved our hypothesis by integrating Th1, Th2 and Th17 cytokines to predict expression of cardiometabolic proteins profiled by OLINK proteomics.

bioinformatics↗

bioRxiv2019

Multiscale analysis of acne connects molecular subnetworks with disease status

Acne vulgaris affects millions of individuals and can lead to psychosocial impairment as well as permanent scarring. Previous studies investigating acne pathogenesis have either examined a targeted set of biological parameters in a modest-sized cohort or carried out high-throughput assays on a small number of samples. To develop a more comprehensive understanding of acne pathophysiology, we conducted an in-depth multi-omic study of 56 acne patients and 20 individuals without acne. We collected whole blood, skin punch biopsies, microbiota from skin follicles, and relevant clinical measurements to understand how multiple factors contribute to acne. We provide an integrative analysis of multi-omics data that results in a molecular network of acne. Comparisons of lesional and non-lesional skin highlighted multiple biological processes, including immune cell and inflammatory responses, response to stress, T cell activation, lipid biosynthesis, fatty acid metabolism, keratinocytes, antimicrobial activity, epithelial cell differentiation, and response to wounding, that are differentially altered in acne lesions compared to non-lesions. Our results suggest baseline differences in the skin that may predispose individuals to develop acne. These datasets and findings offer a framework for new target identification and reference for future studies.

systems biology↗

bioRxiv2017

Genetic Load Makes Cancer Cells More Sensitive To Common Drugs: Evidence From Cancer Cell Line Encyclopedia

Genetic alterations initiate tumors and enable the evolution of drug resistance. The pro-cancer view of mutations is however incomplete, and several studies show that mutational load can reduce tumor fitness. Given its negative effect, genetic load should make tumors more sensitive to anticancer drugs. Here, we test this hypothesis across all major types of cancer from the Cancer Cell Line Encyclopedia, that provides genetic and expression data of 496 cell lines together with their response to 24 common anticancer drugs. We found that the efficacy of 9 out of 24 drugs showed significant association with genetic load in a pan-cancer analysis. The associations for some tissue-drug combinations were remarkably strong with genetic load explaining up to 83% of the variance in the drug response. Overall, the role of genetic load depended on both the drug and the tissue type with 10 tissues being particularly vulnerable to genetic load. We also identified changes in gene expression associated with increased genetic load, which included cell-cycle checkpoints, DNA damage and apoptosis. Our results show that genetic load is an important component of tumor fitness and can predict drug sensitivity. Beyond being a biomarker, genetic load might be a new, unexplored vulnerability of cancer.

cancer biology↗