Lab Research Focus
Research interests involve a wide area of biologically active compounds of natural origin (multidisciplinary approaches to identification, isolation, and analyses of novel compounds, studies on their structure, biosynthesis, and genetics, mode of action and mechanism of resistance), biochemistry and genetics of post-translationally modified peptides and proteins, enzymes and pathways of primary and secondary metabolism and cellular regulations, intercellular communication and signaling, and glycosylated compounds.
Of particular interest more recently are studies on glycosylation of immunoglobulins in health and disease in humans (IgA nephropathy, chronic inflammatory diseases, Kawasaki syndrome) and regulation of immunoglobulin glycosylation.
IgA nephropathy
The hallmark of IgA nephropathy (IgAN), the most common glomerulonephritis in the world, is deposition of IgA1-containing immune complexes into the glomerular mesangium. Proliferation of mesangial cells (MC) and extracellular matrix (ECM) expansion occurs from early stages, progressing into glomerulosclerosis and development of end stage renal disease. High levels of IgA1-containing circulating immune complexes (CIC) are often observed in IgAN patients indicating a defect in CIC clearance. Galactose (Gal) -deficient O-glycans were detected in the hinge region of IgA1 molecules in CIC in IgAN patients. These Gal-deficient IgA1 molecules are complexed with IgG (IgA1) antibodies with anti-GalNAc specificity. Importantly, Gal-deficient IgA1 is also found in kidney immune deposits in IgAN patients. We hypothesize that the glycosylation aberrance of a fraction of IgA1 molecules results in formation of CIC that ultimately deposit in the mesangium, leading to IgAN.
Based on our preliminary results, we postulate that the CIC bind to MC through a novel IgA receptor and possibly other receptors, and trigger signaling events resulting in proliferation of MC and ECM expansion. We have studied interactions of CIC with MC using various approaches, including for example confocal laser scanning microscopy, differential gene and protein expression using DNA arrays and proteomics approaches, respectively. The ultimate goal of these studies is to understand how CIC form, what are major factors inducing aberrant IgA glycosylation, and how CIC trigger pathological response of MC leading to IgAN. We are hopeful that a better understanding of this chronic disease may open new ways for diagnosis or even treatment.
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