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Our laboratory studies the synaptopodin family of actin-associated proteins in health and disease and the cell biology and pathology of kidney podocytes.
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The Synaptopodin Family of Actin-Associated Proteins in Health and Disease
In the center of our research activity is the functional characterization of the synaptopodin gene family of actin-associated proteins. Synaptopodin is the founding member of a class of proline-rich actin associated proteins expressed in specialized, highly dynamic cell compartment such as telecephalic dendrites and foot processes of kidney podocytes.
Synaptopodin promotes RhoA signaling and suppresses Cdc42 signaling. In the brain, synaptopodin deficiency leads to a dramatic reduction of LTP and impaired spatial learning. The kidneys of synaptopodin deficient mice show delayed recovery from experimental proteinuria and bigenic heterozygosity for CD2AP and synaptopodin results in spontaneous proteinuria and FSGS-like kidney damage.
Myopodin, the second member of the synaptopodin gene family, is a dual compartment actin bundling protein that shows a differentiation and stress dependent re-localization between the sarcomeric Z-disc and the nucleus. Myopodin is a signaling protein in the heart and a tumor suppressor in human bladder cancer.
Cell Biology and Pathology of Podocytes
Another major focus in the lab is the cell biology and pathology of podocytes. Podocytes are highly differentiated cells, which play a crucial role in the physiology and pathology of the kidney glomerulus. Podocytes and their slit diaphragms form the final barrier to urinary protein loss. This explains why podocyte injury is typically associated with urinary protein loss.
We uncovered an unanticipated role for costimulatory molecule CD80/B7-1 in podocytes as an inducible modifier of glomerular permselectivity that is independent of T-cells. We found that upregulation of CD80/B7-1 in podocytes contributes to the pathogenesis of proteinuria by disrupting the glomerular filter and provides a novel molecular target to tackle proteinuric kidney diseases.
A combination of genetic, structural, molecular and cell biological approaches is employed to unravel the function of the synaptopodin gene family during synaptic plasticity, in the pathogenesis of proteinuric kidney diseases, and in cardiac development and remodeling. Another major goal is the characterization of kidney podocytes as a novel component of the innate immune system.
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