Alan O. Perantoni, Ph.D.
Dr. Perantoni has devoted his efforts to identifying (1) the ligands responsible for renal progenitor/stem cell survival and differentiation, (2) the molecular targets of those ligands, (3) the mechanisms responsible for the dysregulation of normal signaling in Wilms tumor, and (4) the targets of dysregulation in those tumors.
As Chief, he is responsible for a laboratory dedicated to the analysis of major developmental signaling pathways that contribute to cell growth, differentiation, morphogenesis, and cancer.
Growth/Differentiation Factors in Organogenesis and Their Roles in Tumorigenesis
Morphogenesis in the differentiating metanephros is regulated by reciprocal interactions between ureteric bud (UB) epithelia and the metanephric mesenchyme (MM). The UB invades the overlying MM and induces conversion of the mesenchyme into stromal and epithelial elements, which form the nephron. In turn, the MM stimulates the UB to grow and branch, forming the collecting duct system. The Differentiation and Neoplasia Section focuses on the elucidation of mechanisms of inductive signaling in metanephric development, seeking (1) the ligands responsible for renal progenitor survival and nephronic differentiation, (2) other non-inductive regulatory factors of nephrogenesis, (3) the molecular targets of induction, (4) dysregulation of normal inductive signaling during development of pediatric neoplasms such as the Wilms tumor or congenital mesoblastic nephroma, and (5) targeting the dysregulated signaling in these tumors. The Section uses both explants of metanephric rudiments and mouse genetic models in these studies. We also have ongoing efforts to map the genetic locus responsible for sensitivity to nephroblastoma (Wilms) induction in rats. We expect that as we decipher the roles of various inductive signaling mechanisms in development and understand their dysregulation in tumorigenesis, our studies will lead to novel animal models and targeting agents for drug development.
Selected Key Publications
Preferential Propagation of Competent SIX2+ Nephronic Progenitors by LIF/ROCKi Treatment of the Metanephric Mesenchyme.Stem Cell Reports. Sep 8;5(3): 435-47, 2015. [ Journal Article ]
Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension.Hum Mol Genet. Dec 20;23(25): 6807-14, 2014. [ Journal Article ]
- Nat. Cell Biol. 15: 1035-44, 2013. [ Journal Article ]
- Development. 138: 5369-78, 2011. [ Journal Article ]
- Dev Biol. 352: 58-69, 2011. [ Journal Article ]
Dr. Perantoni received his Ph.D. in cell biology from Catholic University in 1983, having conducted his thesis research at the NCI. After serving as an assistant professor in the Pathology Department, University of Colorado Medical School, he returned to the NCI in 1992.