I. Development and tumorigenesis of the prostate gland.
Our laboratory developed important mouse models for research in prostate development and disease (Wu et al., 2011a), and gathered significant methodological and scientific expertise in regulation of cell fate choice in organogenesis (Grishina et al., 2005; Wu et al., 2009; 2011a,b; Xu et al., 2012; Grishina et al., 2012a,b). We reported that a Tgfb family member, Bone morphogenetic protein 7 (Bmp7), inhibits prostate branching, and signaling by the Notch receptor, which is part of cell fate selection system (Grishina et al., 2005). We further found that upregulation of Notch signaling in a developing prostate is sufficient to induce benign prostate hyperplasia (BPH) in a mouse model (Wu et al., 2011a). We showed that incidence of BPH is mediated by downregulation of the tumor-suppressor Pten, improved maintenance of p63-positive cells in the epithelium and a cell fate shift favoring myoblast over fibroblast lineages in the stroma. A review of ours and others studies on cell fate choice in prostate development and disease is published in a book chapter "Bmp signaling in development and pathologies of the urethra and exocrine glands" in: BMP Signaling: New Research (Grishina et al., 2012a).
II. Developmental causes for cloacal malformations
Several human genetic syndromes, such as Currarino, VACTERL, Hand-Foot-Genital, and Townes-Brocks, manifest in persistent cloaca, imperforate anus and malformations of the external genitalia. In the mouse, as in human, cloaca is a transient embryonic cavity at the caudal end of the hindgut. During normal development, cloaca is separated into the rectal and urethral compartments by the caudal lateral mesenchyme known as the urorectal septum. The ventral cloacal epithelium and mesenchyme contribute to the genital tubercle, the primordium of the penis in males and clitoris in females. We found that mice null for Bone morphogenetic protein 7 (Bmp7) develop persistent cloaca, rectourethral fistula, and malformations of the external genitalia in males and females (Wu et al., 2009). We further showed that Bmp7 induces cloacal septation by regulating cell survival and divisions in the endoderm of the cloacal septum (Xu et al., 2012). We reviewed the current understanding of Bmp functions at multiple stages of cloacal and urethral development in the book chapter (Grishina et al., 2012).
Research Assistant Professor, Department of Urology
Genetic models for genitourinary malformations
Handbook of genitourinary medicine : new research. [S.l. : s.n.], 2013. p.55-67. (1030062)
Defects in the endoderm survival and polarity of cell divisions in the mouse model for rectourethral malformations [Meeting Abstract]
European urology supplements. 2012 Feb; 11(1):E812-U719
PLoS one. 2012; 7(1):e29372-e29372
Developmental biology (Orlando). 2011 Aug 15; 356(2):337-349
Molecular endocrinology. 2011 Jun; 25(6):1018-1026
Bmp7 functions in septation of the murine cloaca by inhibiting the canonical Wnt signaling and favoring planar cell polarity [Meeting Abstract]
Developmental biology (Orlando). 2009 Jul 15; 331(2):443-443
Notch signaling is important for epithelial and mesenchymal organization in the prostate gland [Meeting Abstract]
Developmental biology (Orlando). 2009 Jul 15; 331(2):513-513
Gene expression patterns. 2009 Apr; 9(4):224-230