Our Science – Perantoni Website

Alan O. Perantoni, Ph.D.

Cancer and Developmental Biology Laboratory Head, Differentiation and Neoplasia Section Acting Laboratory Chief National Cancer Institute at Frederick Building 538, Room 224 P.O. Box B Frederick, MD 21702-1201 Phone:   301-846-6529 Fax:   301-846-5946 E-Mail:   peranton@ncifcrf.gov

Biography

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.

Research

Growth/Differentiation Factors in Organogenesis and Their Roles in Tumorigenesis

Our efforts are focused on characterizing the inductive signaling pathways involved in metanephric blastemal cell specification/patterning and those regulatory molecules, both secreted and nuclear, that modulate this process in an effort to define potential targets of carcinogenesis.

The regulation of epithelial morphogenesis is critical for the coordinate development of many adult organ structures. In the differentiating metanephros, this process is regulated by reciprocal interactions between ureteric bud epithelia and the metanephric mesenchyme. The ureteric bud invades the overlying mesenchyme and induces conversion of the mesenchyme into stromal and epithelial elements, giving rise to the polarized tubular and glomerular epithelial structures of the adult nephron. At the same time, the mesenchyme stimulates the ureteric bud to grow, branch, and eventually form the collecting duct system of the adult kidney. The Differentiation and Neoplasia Section has focused on the elucidation of mechanisms of inductive signaling in metanephric development, seeking the ligands responsible for nephronic differentiation, other noninductive regulatory factors of nephrogenesis, and the molecular targets of induction. Previously, we reported the establishment of a cell line derived from the renal inductor, ureteric bud, and have now identified several soluble inductive factors secreted by these cells, including leukemia inhibitory factor (LIF) and transforming growth factor-beta2 (TGFbeta2). These function in combination with FGF2 to yield tubules in culture with kinetics comparable to those found in vivo. We have now also developed an inducible cell line of metanephric mesenchyme that produces epithelial-like structures following treatment with the above described factors. Microarray analyses of the cell lines from bud or mesenchyme have implicated several secreted and nuclear factors in inductive signaling and some of these may function in tumorigenesis as well. These include members of the Wnt pathway, which is required for mesenchymal-epithelial conversion. These findings provide insight into the dynamics and complex interactions that modulate stem cell specification in the kidney, and perturbations of these dynamics, at least in part, may explain the accumulation of stem cell populations in neoplasms such as Wilms’ tumor/nephroblastoma.

Collaborators on this research include Mark Lewandoski, and Jeffrey Rubin, NIH; Mark de Caestecker, Vanderbilt University; and Toshi Shioda, Harvard University.

This page was last updated on 6/12/2008.