Biology subjects

Lac, J.

Publications and source records attributed to Lac, J..

2 recordsLinked to original sources

bioRxiv2025

Computational Modeling and Visualization of Ischemic Effects on an Advanced Purkinje Network

The cardiac Purkinje network plays a vital role in the hearts electrical conduction system, ensuring efficient and synchronized ventricular contraction. When impaired--particularly by ischemia--it can trigger life-threatening arrhythmias. In this study, we present an advanced computational model of the Purkinje network that integrates cell-level heterogeneity, spatial organization, and localized ischemic zones with customizable severity gradients. Developed in Python using open-source libraries (NumPy, matplotlib, pandas, seaborn), the model generates rich visualizations of network structure, conduction velocities, ischemia severity, and electrophysiological parameters. Simulations demonstrate how ischemia alters conduction and refractoriness in a spatially dependent manner, providing insights into arrhythmogenic risk. This modeling framework can advance understanding of cardiac conduction under pathological conditions and support therapeutic development.

bioinformatics↗

bioRxiv2024

Structural basis of TMPRSS11D specificity and autocleavage activation

Transmembrane Protease, Serine-2 (TMPRSS2) and TMPRSS11D are human proteases that enable SARS-CoV-2 and Influenza A/B virus infections, but their biochemical mechanisms for facilitating viral cell entry remain unclear. We demonstrate these proteases can spontaneously and efficiently cleave their own zymogen activation motifs, thereby activating their wider protease activity on other cellular substrates. We determined TMPRSS11D co-crystal structures in complexes with a native TMPRSS11D zymogen activation motif and with an engineered activation motif, providing insights into TMPRSS11D autocleavage activation and revealing unique regions of its substrate binding cleft. We further show that a protease inhibitor that underwent clinical trials for TMPRSS2-targeted COVID-19 therapy, nafamostat mesylate, was rapidly cleaved by TMPRSS11D and converted to low activity derivatives. These insights into human protease viral tropism and into liabilities with existing human serine protease inhibition strategies will guide future drug discovery campaigns for these targets.

biochemistry↗