Harvard Catalyst Profiles

The interplay of the immune and vascular systems is critical for the proper functioning of several processes in the human body. However, the mechanisms regulating vascular function in this context are not well understood. We have identified a novel immune marker, CD70, which is expressed by vascular endothelial and smooth muscle cells and which regulates vasomotor function and inflammation. In this research experience, the student would have the opportunity to learn common methodologies utilized in vascular biology research to understand redox, metabolic, and vasomotor consequences of CD70 expression in the vasculature. This would be an ideal opportunity for students interested in cardiology, vascular medicine, and vascular surgery to gain experience exploring basic mechanisms at the intersection of vascular biology and metabolism that underlie common cardiovascular clinical phenotypes, and for students interested in understanding immune-vascular cross talk.

Non-aortic arterial dissections are increasingly recognized and identified in patients, but a detailed understanding of mechanisms, epidemiology, natural, history, and risk factors is still very rudimentary. While different categories of arteriopathies have been identified, including spontaneous coronary artery dissection, fibromuscular dysplasia, and segmental arterial mediolysis, whether these entities share mechanistic underpinnings is not known. Additionally, arteriopathies demonstrated sex-biased presentations, but the biological basis for this phenotypic expression is unknown. In this research project, we seek to gain greater understanding about arterial dissections using an integrated, bedside-to-benchside approach. We will perform deep phenotyping encompassing clinical parameters, imaging data, and response to therapy for patients with acute presentations of arteriopathies. We will then couple this with a multi-omic characterization of patients to collect transcriptomic, proteomic, and metabolomic level data. Utilizing a network medicine approach, we will then seek to uncover novel disease-associated pathways that are likely to drive the underlying pathobiology and sex-biased phenotype. In this research opportunity, students will engage in clinical/translational research and gain experience with clinical phenotyping and data collection. Depending on the stage of the project, there may be opportunities for multi-omic data analysis and wet-lab validation.