Mark de Caestecker, M.B., B.S., Ph.D.
Division of Nephrology
Renal development, multipotent epithelial progenitor cells, transcription factor, BAC transgenic mice, lineage tracing, cell adhesion, phosphorylation, breast cancer, Wilms tumor, BMP signaling, pulmonary hypertension, vascular remodeling
There are three main areas of research in my lab:
1) One area focuses on the regulation and fate of multipotent epithelial progenitor cells within a discrete cap of cells in the outer rim of the developing kidney that give rise to a variety of complex organized epithelial structures in the adult kidney. We are currently focusing on the role and regulation of Cited family of transcriptional co-factors which are expressed in these cells and in epithelial progenitor cells in the developing breast, and are dynamically regulated during kidney (and breast) development and malignancy. We are using genetic approaches in mice to study the function of these genes during renal development, and are performing studies using BAC transgenic reporter mice to track the fate of cells expressing Cited proteins during normal development. Biochemical (protein-protein interaction screens) and cell culture (adhesion) studies are being used to evaluate the function of Cited1 in kidney and breast epithelial cells, while immunohistochemical and tumor Xenograft studies are being performed to characterize the functional role of Cited proteins in Wilms? tumorgenesis (an embryonal tumor of the kidney).
2) We have recently started a collaborative project with Dr. Neil Hukreide from the University of Pittsburgh in which we are exploring the use and mechanisms by which a new class of histone deacetylase inhibitors, discovered from a high content screen in Zebrafish embryos, enhances renal tubular regeneration and renal progenitor cell numbers in models of acute kidney injury in mice and fish.
3) The other area of research focuses on the functional role of BMP signaling in pulmonary hypertension. Recent studies have shown that patients with a familial form of pulmonary hypertension inherit mutations in the BMP type 2 receptor, BMPR2. Our genetic studies in mice indicate that the signaling pathways that mediate these effects are complex and likely mediate distinct cellular interactions within the pulmonary vasculature. Two of the Bmpr2 ligands, Bmp2 and 4 are expressed by endothelial cells and exert opposing effects on pulmonary vascular smooth muscle cells, while Bmpr2 mutant mice have defective endothelial function associated with increased pulmonary vascular tone. We are currently using BAC transgenic and LoxP mutant mice to evaluate the localization and cell specific function of different Bmp ligands and downstream signaling components in regulating these pulmonary vascular responses. In addition we are evaluating the use of targeted polymeric nanoparticles to modify components in the Bmp signaling pathway in the pulmonary vasculature in rat models of pulmonary hypertension (collaboration with Ales Prokop from the Dept of Chemical Engineering).
Last updated on 2011-10-07