Nowling Research Lab

Tamara M. Nowling, Ph.D.

Professor
Division of Rheumatology & Immunology

The major focus of the Nowling lab is elucidating the role of the glycosphingolipid (GSL) catabolic pathway in the progression of Systemic Lupus Erythematosus (SLE or lupus). SLE is a chronic autoimmune disease characterized by increased production of autoantibodies, formation and deposition of immune complexes (IC) in target tissues, inflammation and tissue damage. The most severe complication of SLE is nephritis, which affects up to two-thirds of lupus patients and is associated with increased morbidity and mortality. The mediators of lupus nephritis remain completely unknown. The GSLs lactosylceramide (LacCer) and glucosylceramide (GlcCer) are elevated in the kidney and urine of lupus mice and human lupus patients with nephritis. The activity of neuraminidase (NEU) is also elevated in the kidney and urine of lupus mice with nephritis.

To better understand the role of the GSL pathway, we are analyzing GSL molecules as potential biomarkers of therapeutic response and determining the molecular and cellular mechanisms by which GSL molecules function in the progression of lupus nephritis. This study involves the analyses of exosomes isolated from urine of lupus nephritis patients to identify lipids and proteins that will serve as potential biomarkers in the response (or lack of response) to treatment. The goal is to generate a panel of biomarkers that can be used to identify patients that will fail to have a therapeutic response to a treatment very early after beginning the treatment and be switched to an alternative treatment to avoid potential organ damage. Additionally, we are analyzing the expression of LacCer/GlcCer, gangliosides and NEUs in renal biopsies from lupus nephritis patients to identify associations with clinical disease measures, as well as performing treatment and genetic studies in lupus prone mouse strains. The ongoing mechanistic studies involve analyzing the expression and role of NEU, LacCer/GlcCer and gangliosides in the activation and function of renal cells and inflammation. These studies utilize mesangial cells isolated from kidneys of healthy and lupus prone mice without and with a knockout of the Neu1 gene. These studies are currently supported in part by a grant from the DoD.

Publications

PubMed Collection

Senior Author Publications

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