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Growth Factors

BASIC science

acute kidney injurychronic kidney diseasediabetic nephropathydevelopmentmatrix biology, hypertension,integrin biology,  eicosanoid biologygene delivery, endotheiall cell biology, bioartificial kidney


 

                                Growth Factors

Members of the VCKD are investigating the roles and mechanisms of growth factors in kidney disease.

 

Director

MEMBERS

The de Caestecker lab is studying the role and regulation of the retinoic acid signaling pathway in mediating renal cellular injury and repair mechanisms after acute kidney injury (AKI). His laboratory is evaluating new thereutic strategies to enhance this cellular repair mechanism in order to accelerate recovery and reduce long-term fibrosis and chronic kidney injury after episodes of AKI.

The Fogo laboratory studies mechanisms of progression of kidney disease and potential regression of glomerulosclerosis. The laboratory focuses on key interactions of glomerular cells, and the effects of the renin angiotensin system and plasminogen activator inhibitor-1 (PAI-1) on these interactions, using genetically engineered mice and cell culture.

The Gewin lab studies how growth factors, in particular those of the TGF-beta superfamily, modulate the renal response to acute and chronic kidney injury. The lab is particularly interested in the cell-specific effects of growth factors on renal injury and uses genetically modified mouse models as well as cell culture techniques to investigate the differential effects of growth factors on epithelial and mesenchymal cells.

The Haase lab studies HIF oxygen-sensing pathway and uses conditional gene targeting technology and transgenesis, as well as biochemical and functional genomics approaches to define the specific roles of HIF transcription factors in tumorigenesis, acute ischemia and chronic hypoxic injury, as well as erythropoiesis and iron metabolism. Hypoxia-Inducible Factors HIF-1 and HIF-2 are oxygen-sensitive basic helix-loop-helix transcription factors, which regulate biological processes that facilitate both oxygen delivery and cellular adaptation to oxygen deprivation. HIFs consist of an oxygen-sensitive alpha-subunit, HIF-alpha and a constitutively expressed beta-subunit, HIF-beta, and regulate the expression of genes that are involved in energy metabolism, angiogenesis, erythropoiesis and iron metabolism, cell proliferation, apoptosis and other biological processes. Since HIF increases the expression of cytoprotective factors and erythropoietin, pharmacologic inhibition of HIF-alpha degradation offers significant potential for the treatment of acute hypoxic injuries and anemia.

The Harris lab has a long standing interest in the role of the ErbB family of receptors and ligands in kidney physiology and pathophysiology. The lab has identified an important role for EGFR (ErbB1) activation in recovery from acute kidney injury and a detrimental role for persistent and aberrant EGFR activation in chronic kidney injury, including progressive tubulointerstitial fibrosis and diabetic nephropathy. In addition, the lab is actively investigating the role of another member of this receptor family, ErbB4, in renal development and pathophysiology.

The Pozzi lab studies the molecular mechanisms whereby EGF and TGF-β receptors control glomerular and tubular cell homeostasis in healthy and diseased kidneys. We focus our research on the interplay between these two receptors and the matrix receptors integrins α1β1 and α2β1 in the regulation of cell homeostasis in the course of kidney glomerular and tubular injury.

The Takahashi lab has been studying the role of CD148 tyrosine phosphatase in renal endothelial or epithelial cells. The lab has demonstrated that CD148 tyrosine phosphatase serves as a negative regulator of growth factor signaling, including VEGF, HGF and EGF, and inhibits endothelial and epithelial cell proliferation and migration. Further, more recently, the lab found that thrombospondin-1 acts as a functionally important ligand for CD148. The lab is currently investigating the role of this pathway in kidney disease, including diabetic nephropathy and renal fibrosis.

The Zent laboratory studies the interactions between integrin- and growth factor-dependent signaling in kidney development, function and pathology. We utilize both in vivo and in vitro models and employ cell biology and biochemistry to study this relationship.

The Zhang lab is studying the potential roles of growth factors such the EGFR pathway in collaboration with Harris lab in the pathogenesis of AKI and diabetic nephropathy.