Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies.

A one-two punch sequential regimen of senescence-inducing agents followed by senolytic drugs has emerged as a novel therapeutic strategy in cancer. Unfortunately, cancer cells undergoing therapy-induced senescence (TIS) vary widely in their sensitivity to senotherapeutics, and companion diagnostics to predict the response of TIS cancer cells to a specific senolytic drug are lacking. Here, we hypothesized that the ability of the BH3 profiling assay to functionally measure the mitochondrial priming state-the proximity to the apoptotic threshold-and the dependencies on pro-survival BCL-2 family proteins can be exploited to inform the sensitivity of TIS cancer cells to BH3-mimetics.

Fatty acid synthase (FASN) is a tumor-cell-intrinsic metabolic checkpoint restricting T-cell immunity.

Fatty acid synthase (FASN)-catalyzed endogenous lipogenesis is a hallmark of cancer metabolism. However, whether FASN is an intrinsic mechanism of tumor cell defense against T cell immunity remains unexplored. To test this hypothesis, here we combined bioinformatic analysis of the FASN-related immune cell landscape, real-time assessment of cell-based immunotherapy efficacy in CRISPR/Cas9-based FASN gene knockout (FASN KO) cell models, and mathematical and mechanistic evaluation of FASN-driven immunoresistance.

Computational modeling of angiogenesis: The importance of cell rearrangements during vascular growth.

Angiogenesis is the process wherein endothelial cells (ECs) form sprouts that elongate from the pre-existing vasculature to create new vascular networks. In addition to its essential role in normal development, angiogenesis plays a vital role in pathologies such as cancer, diabetes and atherosclerosis. Mathematical and computational modeling has contributed to unraveling its complexity.

Whole Genome Sequencing for Studying Antimicrobial Resistance.

Antibiotic resistance (AMR) is an alarming concern worldwide and , one of the most prevalent bacteria, is not an exception. With antibiotics being its primary therapy, increasing resistance leads to a higher rate of treatment failure. Understanding the genomic mechanisms of resistance to clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline, and rifampicin through next-generation sequencing-based molecular tools, such as whole genome sequencing (WGS), can be of great value, not only to direct a patient's treatment, but also to establish and optimize treatment guidelines according to the local epidemiology and to avoid the use of inappropriate antibiotics.