Biology subjects

Conlon, T. M.

Publications and source records attributed to Conlon, T. M..

3 recordsLinked to original sources

bioRxiv2026

A generative AI framework for disease-specific lung microtissue bioengineering

Generative Lung Architecture Modeling (GLAM) is an integrated bioengineering framework that couples high-resolution three-dimensional tissue imaging with generative artificial intelligence to de novo design and 3D-bioprint anatomically detailed lung microtissue models. Native extracellular 3D matrix architectures of pulmonary parenchyma were extracted from healthy, fibrotic, and emphysematous in vivo mouse disease models and processed through a computational pipeline containing pre-trained image segmentation and 3D mesh generation. The resulting datasets were used to train a U-Net generative diffusion model with attention layers capable of synthesizing healthy and diseased lung tissue architectures. Microtissue cubes of about 200 - 300 {micro}m edge length of native and synthetic datasets were fabricated through high-resolution two-photon stereolithography with gelatin-methacryloyl biomaterial ink and successfully seeded with cells, demonstrating biological compatibility. In closing the loop between biological imaging, generative modeling, and high-resolution biofabrication, this integrated framework establishes generative AI as a functional design layer for tissue engineering. The resulting lung microtissues retained architectural features of the native and original tissues, making them an application-ready platform for customizable and scalable fabrication of biological tissue surrogates for preclinical modeling, drug testing, and precision regenerative bioengineering.

bioengineering↗

bioRxiv2021

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here we utilized a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors of which we screened the function in lung organoids. We found several drug targets with regenerative potential of which EP and IP prostanoid receptor ligands had the most significant therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we discovered by using scRNA-sequencing analysis that circadian clock and cell cycle/apoptosis signaling pathways were enriched in alveolar epithelial progenitor cells in COPD patients and in a relevant model of COPD, which was prevented by PGE2 or PGI2 mimetics. Conclusively, specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.

pharmacology and toxicology↗

bioRxiv2020

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis.

bioinformatics↗