Nowling Research Lab

Professor
Division of Rheumatology & Immunology

The major focus of the Nowling lab is elucidating the role of glycosphingolipid (GSL) metabolism in the progression of Systemic Lupus Erythematosus (SLE or lupus). SLE is a chronic autoimmune disease characterized by increased production of autoantibodies, formation / deposition of immune complexes in target tissues, inflammation, and tissue damage. The most severe complication of SLE is nephritis (lupus nephritis), which affects up to two-thirds of lupus patients and is associated with increased morbidity and mortality. The mediators of lupus nephritis remain incompletely known. The Nowling lab in collaboration with several other labs was the first to demonstrate that the GSLs lactosylceramide (LacCer) and glucosylceramide (GlcCer) are elevated in the kidney and urine of lupus mice and human lupus patients with nephritis, suggesting they play a role in disease progression. Further studies from the Nowling showed that the levels of these GSLs were significantly elevated prior to treatment in lupus nephritis patients who did not respond to standard of care treatment compared to patients who had a complete response. We are also analyzing changes in N-linked glycosylation (N-glycans) from proteins present in the urine and serum of lupus nephritis patients. Our collaborative group showed altered levels of N-glycans in lupus patients with nephritis, and we are analyzing N-glycan changes with respect to disease progression and therapeutic response. The goal is to identify changes in the urine glycomic profiles (GSLs and N-glycans) that can serve as biomarkers of disease and potentially predict which patients are unlikely to respond to standard therapies.

In addition to the biomarker studies, the Nowling Lab investigates the cellular and molecular mechanisms by which GSL metabolism impacts the function of renal cells in the progression of lupus nephritis. In these studies, the lab uses primary human renal mesangial cells and glomerular endothelial cells in monocultures and co-cultures, as well as isolated intact glomeruli to elucidate effects on pathological responses to inflammatory stimuli and cell-cell communication. Currently the lab is focused on sex differences in GSL metabolism in the pathological responses of renal cells, specifically how GSLs modulate cellular stress / endoplasmic reticulum (ER) stress in response. The lab also utilizes well-established pre-clinical mouse models of lupus to better understand and translate observations in cell cultures to disease pathology. The Nowling lab is highly collaborative with ongoing robust studies with colleagues in the areas of renal physiology, renal endothelial function, imaging mass spectrometry, and biostatistics. Importantly, the Nowling strongly supports and values diverse viewpoints, ideas, and contributions, which serves to ensure robust and innovative research.

Publications

PubMed Collection

Senior Author Publications

Senior Author PubMed Collection (senior author publications are most often associated with mentored projects)