Department Molecular Genetics
Principal investigator Jeroen Essers
E-mail address j.essers@erasmusmc.nl
Website https://www.erasmusmc.nl/en/research/researchers/essers-jeroen
Investigating Molecular Phenotypes of ACTA2 Variants in Thoracic Aortic Aneurysm and Dissection
Supervisor: Jeroen Essers, j.essers@erasmusmc.nl
ACTA2, the gene encoding smooth muscle alpha-actin, plays a crucial role in vascular smooth muscle cells (VSMCs). Mutations in ACTA2 are significant contributors to early onset thoracic aortic aneurysms and dissections (TAAD). This research project aims to elucidate the molecular phenotype of pathogenic and likely pathogenic (P/LP) variants in the ACTA2 gene to improve the interpretation of variants of unknown significance (VUSs) as well as the mechanistic interaction between ACTA2 mutations and the unfolded protein response which we have recently discovered, ultimately enhancing patient management and treatment strategies.
Techniques
- Cell Culture: Primary dermal fibroblasts from patients with P/LP ACTA2 variants and control subjects
- Protein structure: prediction and analysis.
- TGFβ Stimulation: Induce transdifferentiation into smooth muscle-like cells.
- Functional Assays: Immunofluorescent staining, Western blotting, and fiber organization analysis.
Further reading
de Wagenaar NP, van den Bersselaar LM, Odijk HJHM, Stefens SJM, Reinhardt DP, Roos-Hesselink JW, Kanaar R, Verhagen JMA, Brüggenwirth HT, van de Laar IMBH, van der Pluijm I, Essers J. Functional analysis of cell lines derived from SMAD3-related Loeys-Dietz syndrome patients provides insights into genotype-phenotype relation. Hum Mol Genet. 2024 Jun 5;33(12):1090-1104. doi: 10.1093/hmg/ddae044. PMID: 38538566; PMCID: PMC11153339.