Mark P. de Caestecker, M.B.B.S., Ph.D.

There are three main areas of research in my lab: 1) Our laboratory is interested in the mechanisms regulating kidney development and how these processes are abnormally regulated in kidney injury and malignancy (Wilms tumor). Studes from my lab have mainly focused on the role of Cited1, 2 and 4, a family of transcriptional co-activators that are involved in regulating fate and migration of epithelial progenitor cells in during renal development. In addition, based on our evaluation of Cited1 knockout mice, we are investigating the fetal programming defects resulting from intrauterine growth retardation that promote abnormal embryonic kidney development and chronic kidney disease in adults. 2) We are currently extending our developmental studies to explore how some of these developmental regulated pathways are reactivated in regerenating tissues following acute kidney injury and studying their role in promoting normal tissue regeneration. Based on these studies we are testing novel thereapeutic approaches, identified from high content screens in zebrafish embryos (in collaboration with Neil Hukreide from the University of Pittsburgh) , that enhance these regnerative developmental programs, increase the rate of recovery and reduce long term scarring following acute kidney injury in mice. 3) The other focus in my lab is on the functional role of BMP signaling in pulmonary hypertension. Human genetic studies indicate that this signaling pathway plays an important role in modifying pulmonary vascular responses in disease. Studies from my lab have shown that Bmp signaling exerts distinct opposing, cell specific effects on pulmonary vascular remodeling and tone. We are currently using genetic models in mice and patient derived IPS cells to evaluate effect of inherited mutations in the BMP type 2 receptor, BMPR2, on pulmonary vascular cell function, and using these approaches to evaluate the use of mutation-specific therapies to improve pulmonary vascular function in patients with heritable forms of pulmonary hypertension