Biology subjects

Lin, J. S.

Publications and source records attributed to Lin, J. S..

4 recordsLinked to original sources

bioRxiv2026

LIN-44/Wnt controls developmental neurite pruning via UNC-43/CaMKII and PKC-2/PKC in C. elegans

During development, many neurons prune their neurites. While many pruning events are activity-dependent, some neurons undergo stereotyped and developmentally regulated neurite pruning, and our understanding of the signaling pathways that mediate this form of pruning remains limited. In this study, using the PDB motor neuron in C. elegans, we show that the Wnt-calcium signaling pathway is required for stereotyped neurite pruning during development. We found that mutants of itr-1/IP3 receptor and two calcium-dependent kinases, unc-43/CaMKII and pkc-2/PKC, exhibit neurite pruning defects. Genetic analysis suggested that they function downstream of lin-44/Wnt in neurite pruning. Human CaMKIIA can induce neurite pruning in C. elegans, and mutations in CaMKII genes in patients with intellectual disabilities affect its pruning function. In vivo calcium imaging revealed that PDB neurites exhibit calcium transients during neurite pruning, which are regulated at least in part by lin-44 and itr-1. Furthermore, we demonstrate that pkc-2 regulates neurite pruning through clathrin-mediated endocytosis. Together, our work reveals the critical functions of Wnt-calcium signaling in neurite pruning.

neuroscience↗

bioRxiv2025

Targeting intracellular of populations Pseudomonas aeruginosa with peptide-mimetic therapies: individual efficacy and synergistic rescue of obsolete antibiotics.

Pseudomonas aeruginosa is a leading cause of human infections, with current treatment options severely limited by high levels of antimicrobial resistance. Historically considered to be an extracellular pathogen, recent evidence has emerged that P. aeruginosa is able to survive and replicate within human cells. These intracellular niches present an additional clinical challenge and may serve as bacterial reservoirs associated with chronic infections that are particularly difficult to eradicate. Here we describe the application of a novel peptide-based therapeutic against recalcitrant populations of bacteria residing within lung epithelial cells. This antimicrobial "peptoid" is able to target intracellular bacteria without harming host cells. In addition, we have shown that peptoid TM5 exhibits synergy with three antibiotics that otherwise have low efficacy against P. aeruginosa, effectively rescuing drugs that have become clinically obsolete. These synergistic combination therapies are also capable of reducing intracellular bacterial reservoirs, opening the door for potential new strategies against chronic P. aeruginosa infections.

microbiology↗

bioRxiv2025

Longitudinal T cell repertoire analysis reveals dynamic clonal T cell populations in Ulcerative Colitis

BackgroundUlcerative Colitis (UC) is characterized by chronic, relapsing and remitting inflammation in the colon and rectum. Pathogenic T cell activity is thought to play a major role in this process. T cell effector function is determined by the T cell receptor (TCR) and the antigen it recognizes. Examining the TCR repertoire can provide key insights into the adaptive immune response. ObjectiveTo characterize the longitudinal TCR repertoire of patients with UC across disease activity to determine if recurrent antigen(s) are responsible for active inflammation. DesignBulk TCR V{beta} sequencing was done on colon tissue of 20 patients with UC across multiple time points of disease. Corresponding clinical metadata was also obtained over the same time period for each patient to map their clinical disease course. The top ten most highly abundant clones from each time point were longitudinally tracked and correlated with disease phenotype. ResultsSeventy-five percent of patients did not have overlapping abundant TCR clones across multiple time points of disease. The remaining 25% of patients had one to five TCR clones present in high abundance in their tissue during every time point analyzed. ConclusionThese results demonstrate that most patients with UC do not share a similar TCR repertoire over time, indicating that times of inflammation are associated with unique antigen exposures. A smaller group of patients have persistent, private TCR clones with high abundance, 60% of whom had more unremitting, active disease.

immunology↗

bioRxiv2023

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

The rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year. Pseudomonas aeruginosa, in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2,000 deaths annually. While the emergence of resistant bacteria has become concerningly common, identification of useful new drug classes has been limited over the past 40+ years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity for mammalian cells to allow for use in treatment of infections. Interestingly, TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30-60 minutes in vitro, and is effective against a range of clinical isolates. In vivo, TM5 significantly reduced bacterial load in the lungs within 24 hours compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDR P. aeruginosa respiratory infections.

microbiology↗