RNA sequencing and proteomics analysis to identify molecular pathways implicated in the development of aortic aneurysms

Adviser: Dr. Francesca Seta, Vascular Biology Section at the Boston University School of Medicine

Project Description: Cardiovascular diseases remain the leading cause of morbidity and mortality in USA. Dr Seta’s research focuses on cellular and molecular mechanisms of vascular diseases, with the goal of identifying novel therapeutic targets. Ongoing studies are examining the role of the transcription factor Bcl11b and the enzyme sirtuin-1 on the development of aortic aneurysms, abnormal aortic dilations for which there is no targeted therapies. We found that both proteins are protective against aortic aneurysms, as demonstrated in mice with Bcl11b or Sirtuin-1 deletion, which develop aortic aneurysms or ruptures when treated with the hypertensive agent angiotensin II (see Valisno et al Circ Research 2021 and Fry et al, JAHA 2015). However, the molecular mechanisms by which these proteins exert their beneficial effects is elusive. To address this, we ran both RNA sequencing and proteomics analysis on aortas from angII-treated controls and mice with either Bcl11b or sirtuin1 deletions to identify downstream transcriptomics and proteomics pathways. We would like to analyze these datasets and possibly integrate them to identify the molecular pathways involved in the formation of aortic aneurysms.