Giachelli Lab

Our research is focused on elucidating and blocking calcific pathways.

 

Molecular mechanisms involved in CAVD

Calcific aortic valve disease (CAVD) is a common disease in the aging population and is present in about 2% of the population over the age of 65. CAVD is characterized by phenotypic changes including extra cellular matrix remodeling, osteochondrogenic differentiation and calcification, as well as molecular changes involving changes in expression of myofibroblast marker proteins (SM22, SMA), transcription factors (SOX9, RUNX2) and secreted factors (BMP and TGF-β). At present, the only available treatment option is surgical replacement of the diseased valve. We hypothesize that in CAVD, RUNX2 is upregulated in aortic valvular interstitial cells (VICs) and this is essential for osteochodrogeneic differentiation of the VICs as well as the procalcific changes in the aortic valve. On the other hand, SOX9, which we hypothesize is required for mediating the reparative phenotype, is downregulated in the aortic valves. These studies will identify the lineage of RUNX2 positive osteochondrogenic precursor cells, and potential mechanisms for activation of these factors.

 

Inflammatory Response of Microvascular Endothelial Cells to Monocytic Adhesion in Pediatric Cardiopulmonary Bypass Cases

Objective: to study how monocytes activated through shear stress in the CPB setup affect endothelial junctions and the trans-endothelial migration of monocytes.

The use of the cardiopulmonary bypass (CPB) system is closely associated with the well-being of pediatric patients with congenital heart diseases (CHD). The poorly characterized CPB conditions in pediatric patients, such as flow rates and shear stress, frequently lead to clinical complications associated with endothelial activation, such as cytokine release, inflammatory cell invasion, vascular leak and multi-organ dysfunction. There is need to study shear-induced endothelial inflammation in CPB for the development of new therapeutic strategies.

 

Investigating the role of sodium phosphate co-transporters in vascular calcification in a chronic kidney disease model.