The research focus areas in the Moeckel lab are centered on the vascular and cellular biology of acute kidney injury and progression of chronic kidney disease:

  1. Cell survival mechanisms under hypertonic conditions: the focus is on COX2-dependent survival of renal medullary cells and the role of chaperones such as organic osmolytes and heat shock proteins in preventing apoptosis.
  2. The role of hyperphosphatemia in progression of chronic kidney disease (CKD): phosphate-induced AKI and progression of interstitial fibrosis and the molecular mechanisms thereof.
  3. Cell-matrix interaction and its role in cell volume regulation: cytoplasmic membrane and cytoskeleton proteins stimulate signaling pathways that regulate osmo-adaptive responses and cell volume.
  4. The role of renal fibroblasts in progression of diabetic nephropathy: we examine the molecular mechanisms how high glucose stimulates collagen and fibronectin synthesis in cortical and medullary fibroblasts.

Hyperosmotic stress is highly prevalent in the kidney medulla and how cells survive in this lethal environment is largely unknown. Medullary interstitial cells contain very high concentrations of cyclooxygenase 2 (COX2) that synthesizes the prostanoids PGE2 and PGI2, which are important in mediating cell survival under hyperosmotic conditions. Our lab discovered that COX2 activity is an important regulator of the compatible osmolyte response in medullary kidney cells and that Integrins play an important role in the cell-matrix interaction that leads to accumulation of compatible osmolytes and cell volume regulation. The mechanisms employed by kidney cells to sense the hypertonic environment and communicate this signal to transcription factors such as TonEBP/NFAT5, which subsequently drive the expression of osmolyte transporters and heat shock proteins, is one focus of our studies.

Renal fibroblasts play an important role in the development of interstitial fibrosis and progression of CKD. Our lab is currently investigating the mechanisms that lead to increased synthesis of fibrogenic molecules such as fibronectin and collagen in renal fibroblasts under hyperphosphatemic and hyperglycemic conditions. We have generated primary and immortalized fibroblast cell lines from renal cortex and medulla, which we employ to study signaling pathways and the regulation of transcription factors that drive progression of fibrosis. Moreover, we are investigating the role of endothelial cell injury in progression of renal fibrosis using diabetic mouse models.

Lab Experience

Students and post-docs in my lab are exposed to a wide variety of physiologic, biochemical, cell biological, molecular and cell and tissue organ culture techniques as well as several animal models utilizing transgenic and knock-out technologies. Moreover, the student will be exposed to human kidney biopsy material in an attempt to correlate findings in the animal and cell culture models with actual patient kidney pathology.