Funded Projects

Systematic lupus erythematosus (SLE) is a complex autoimmune disease, with prevalence in the adult U.S. population estimated at 24-150 cases per 100K patients. At least 5 out of 10 SLE adults develop lupus nephritis (LN), and depending on the disease classification, up to 30% of patients progress to renal failure within 15 years. Existing methods to score histological activity and chronicity from LN renal biopsies correlate poorly with the progression of LN, and inadequately predict LN outcome from initial biopsies. Neutrophils and their extracellular defense mechanisms such as NETs (neutrophilic extracellular traps) have been implicated in autoimmune diseases. NET’s detected in glomeruli of human LN renal biopsies have been correlated with proteinuria and may play a role in LN progression. Rigorous computational and biological tools to quantify and understand NET functionality in whole slide images (WSIs) of LN biopsies have yet to be established. Such tools would clarify the role of NETs, as potential digital early-indicators of LN outcome, and may shed light on the chronic pathogenesis of LN. Our interdisciplinary team, with expertise in neutrophil biology and imaging (Dr. Michelle Visser), computational renal pathology (Dr. Pinaki Sarder), and 3D anatomical modeling (new UB faculty Dr. Jack Tseng), is interested in understanding the role of NETs in LN. We will 1) use immunofluorescence and landmark-based 3D geometric approaches to accurately study NETs in LN tissue biopsies and 2) develop computational methods to detect, segment, and quantify NETs detected in LN renal biopsies from fluorescence microscopy images of thin renal tissue sections. This proposal will allow us to generate data for future grant proposals examining NET functionality during LN, as well as potential novel diagnostic tools.