Research in the St. Hilaire Lab focuses on identifying and characterizing the mechanisms underlying the development of vascular and valvular calcification pathologies and bioprosthetic valve failure, with specific interest in defining the mechanisms by which genetic mutations, inflammation, and mechanical stress drive the transformation of a healthy cells into calcifying cells. For these investigations the St. Hilaire Lab obtains human tissues from patients with various cardiovascular diseases, utilizes murine models and primary human patient cells and tissues to create in vitro and ex vivo disease models, and performs biochemical, biomechanical, molecular biology, and next generation sequencing techniques.

We are seeking a highly motivated Postdoctoral Fellow to join our team investigating the molecular mechanisms driving Medial Arterial Calcification (MAC), a distinct cause of peripheral artery disease (PAD) independent of atherosclerosis. This research stems from our groundbreaking study that identified mutations in CD73 as the cause of a rare MAC disorder. We are now focused building on our data identifying a paradigm where the DNA damage response (DDR) serves as a primary driver of vascular stiffness and osteogenic reprogramming. Specifically, the project explores how genotoxic stress and the loss of DNA repair enzymes, such as Ercc1, trigger a signaling cascade that represses CD73 expression, disrupts vascular homeostasis, and initiates the transition of smooth muscle cells (SMCs) toward a bone-like phenotype.

The successful Candidate will lead experimental efforts to elucidate the contribution of DDR to MAC, and expand the scope of our study to investigate how cardiovascular calcification is accelerated by the unique stressors of deep space, such as radiation and microgravity. Utilizing a combination of primary human coronary and tibial artery SMCs alongside a novel stochastic DNA damage mouse model, the fellow will perform biochemical and molecular pathway mapping. This work leverages cutting-edge multi-omics, including single-cell transcriptomic analysis and RNAScope on human MAC tissues, to define the spatial and transcriptional landscape of calcified vessels. This role is centered on defining how cellular responses to DNA damage promote pathological remodeling. The Candidate will be responsible for evaluating these pathways as therapeutic targets, conducting rigorous in vitro and in vivo testing to determine if modulating the DDR or its immediate downstream effectors can rescue the calcification phenotype and restore vascular function.

Minimum requirements – PhD in biochemistry, molecular biology, genetics, or similar science with experience in vascular biology

 Interested Applicants should apply via join.pitt.edu requisition #26002720 and attach a CV and cover letter.