Alan O. Perantoni, Ph.D.
Cancer and Developmental Biology Laboratory
Building 539, Room 223A
Frederick, MD 21702-1201
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.
Hall MD, Murray CA, Valdez MJ, Perantoni AO. Mesoderm-specific Stat3 deletion affects expression of Sox9 yielding Sox9-dependent phenotypes. PLoS Genet. 2017;13(2):e1006610.
Tanigawa S, Sharma N, Hall MD, Nishinakamura R, Perantoni AO. Preferential Propagation of Competent SIX2+ Nephronic Progenitors by LIF/ROCKi Treatment of the Metanephric Mesenchyme. Stem Cell Reports. 2015;5(3):435-47.
Yun K, Ajima R, Sharma N, Costantini F, Mackem S, Lewandoski M, Yamaguchi TP, Perantoni AO. Non-canonical Wnt5a/Ror2 signaling regulates kidney morphogenesis by controlling intermediate mesoderm extension. Hum Mol Genet. 2014;23(25):6807-14.
Das A, Tanigawa S, Karner CM, Xin M, Lum L, Chen C, Olson EN, Perantoni AO, Carroll TJ. Stromal-epithelial crosstalk regulates kidney progenitor cell differentiation. Nat Cell Biol. 2013;15(9):1035-44.
Kitagaki J, Ueda Y, Chi X, Sharma N, Elder CM, Truffer E, Costantini F, Lewandoski M, Perantoni AO. FGF8 is essential for formation of the ductal system in the male reproductive tract. Development. 2011;138(24):5369-78.
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This page was last updated on June 15th, 2017