The focus of Kurt Amsler’s research throughout his career has been to understand the functioning and regulation of epithelial tissues in health and disease. In one avenue of investigation, Amsler demonstrated that epidermal growth factor receptor mislocalized to the apical membrane of renal epithelial cells, as occurs in polycystic kidney disease (PKD), exhibits abnormal and prolonged signaling. Inhibition of signaling by this and the related HER2 receptor, which is overexpressed in PKD, inhibits disease progression in multiple mouse PKD models. This finding suggests a potential therapeutic approach to this disease.
Another aspect of Amsler’s research has focused on the mechanisms and regulation of the movement of molecules across the epithelium. Previous work examined the function and role of several transporters, including the Na+-D-glucose symporter, the Na+/H+ antiporter, and the Na+-K+-2 Cl- symporter in renal and other epithelia.
Recent work from Amsler’s research group focuses on the mechanism and regulation of the paracellular movement of large molecules across renal epithelia (Leak Pathway) under normal and pathologic conditions (for example, in renal ischemia/reperfusion injury). These studies have demonstrated a role for the ERK 1/2 signaling pathway and the tight junction-associated protein ZO-1 in the regulation of Leak Pathway permeability. In collaboration with other research groups, Amsler’s group is beginning to define the molecular basis for the Leak Pathway and how it is regulated in physiological and pathophysiological conditions.
- Src Family Kinases and control of epithelial cell paracellular permeability (NIH R15DK091749)
- Caswell D., Jaggi S., Axis J., Amsler K. Src Family Kinases Regulate Renal Epithelial Cell Paracellular Permeability Independent of Occludin Protein. J Cell Physiol 228:1210-1220, 2013. doi: 10.1002/jcp.24274. Epub 2012 Nov 6; PMID:23129414.
- Janosevic D., Axis J., Bacallao R. L., Amsler K. Occludin content modulates hydrogen peroxide-induced increase in renal epithelial paracellular permeability. J Cell Biochem 117:769-779, 2016. doi: 10.1002/jcb.25362. Epub 2015 Sept 17; PMID:26348235.
- Bilal S., Jaggi S., Janosevic D., Shah N., Teymour S., Voronina A., Watari J., Axis J., Amsler K. ZO-1 protein is required for hydrogen peroxide to increase MDCK cell paracellular permeability in an ERK 1/2-dependent manner. Am J Physiol 315:C422-C431, 2018. Doi: 10.1152/ajpcell.00185.2017. Epub 2018 Jun 6. PMID:29874107.
Courses I Teach/Have Taught at NYIT
- Epithelial transport physiology
- Renal physiology
- Advanced Concepts in Neuromusculoskeletal Sciences