The Salem Lab employs state-of-the-art technologies, primarily CRISPR-Cas9 and engineered prime editors, to model human cardiovascular diseases in rodents and cell lines. Our research focuses on key genes that regulate vascular smooth muscle cell (VSMC) dedifferentiation and proliferation under disease conditions, the so-called phenotypic switching.
We also leverage advanced gene delivery techniques, such as adenoviral vectors, to selectively target VSMCs. In addition, we employ cutting-edge multi-omics approaches to investigate the fate and state of VSMCs in various disease contexts.
A new direction in the lab is to understand the 3D genomic organization in vascular diseases using Hi-C and other chromosome conformation capture techniques. Mapping chromatin interactions will help us to identify enhancer-promoter interactions that drive VSMC phenotypic transitions and detect structural variants that alter gene expression and regulation in disease states.
Beyond molecular studies, we integrate physiological assessments, including blood pressure measurement, atherosclerosis progression, and aneurysm formation, to gain a comprehensive understanding of disease mechanisms.
CURRENT PROJECTS
- Transcriptional regulation and genomic landscape of MEIS1 in VSMCs
- Development of novel mouse models to investigate MEIS1 function in vascular disease
- Characterizing the impact of LMOD1, a novel CAD risk allele, on cargo motility in VSMCs
- Hi-C analysis of chromatin architecture in human and mouse VSMCs
- Genome-editing approaches to model human vascular disease in rodents
