Sandra Merscher, PhD

Using a basic science and translational research approach, my laboratory is focused on elucidating and understanding the molecular mechanisms that contribute to the development of proteinuria with a focus on focal segmental glomerulorsclerosis (FSGS) and diabetic kidney disease (DKD).

One area of our research focuses on investigating a novel mechanism by which rituximab, an antibody that has been developed to target B-lymphocytes for the cure of lymphoma, may directly protect podocytes in focal segmental glomerulosclerosis (FSGS). In this study, we are determining if rituximab treatment administered to high-risk patients at time of transplantation protects from recurrent FSGS. Kidney biopsies and a cell-based assay in which human podocytes are cultured in the presence of sera from patients with FSGS are used to determine if rituximab directly protects from podocyte injury through a novel pathway (Science TM, 2011). Our research in this area may lead to a novel clinical indication for rituximab, it may unveil novel targets for antiproteinuric drug development, and may lead to the development of an assay for the pre-transplant identifications of patients at risk for recurrent disease.
The second area of our research focuses on investigating the role of cholesterol accumulation in DKD. We previously described that decreased expression of ABCA1 in podocytes is associated with cholesterol accumulation and apoptosis (Diabetes, 2013). We are investigating the mechanisms leading to decreased expression of ABCA1, cholesterol accumulation, podocyte malfunction, proteinuria and DKD progression using a combination of in vitro and in vivo approaches. Established mouse models for T2D are furthermore used to investigate the potential of Cyclodextrin as a drug to prevent proteinuria and podocytopenia in DKD.