Roles of LNCIB-Functional Genomics ( PI dr. C. Schneider ):

(1) involvement in the construction of full-length enriched cDNAs is based on the biotinylated CAP trapper methodology co-developed with RIKEN-Japan for the mouse transcriptome (Carninci P,. et al Genomics. 1996 37(3):327-36, Okazaki Y et al. Nature. 2002 420,563-73). LNCIB has compiled a set of 15 K human full-length-enriched cDNAs catalogued by 5’-end sequence of cDNAs derived from various human-fetal tissues and directionally cloned in pGATEWAY-vector for subsequent functional studies (Dalla E. et al Ms in preparation). It represents the starting resource to be be implemented in the course of this project with the introduction of new cancer-related cDNAs and compilation of a comprehensive data-base containing the 5’-genomic-contour regions for integration with microarray for gene-networking analysis.

(2) involvement in functional-genomics studies of basic cancer-pathways is based i) on the use of yeast-two-hybrid and relevant biochemical/cell-biological assays as read-out for new regulators of the following pathways: p53, gas6/AxlRTK, apoptotic pathways and beta-catenin, (see Refs) ii) establishment and use of an in-house cDNA-microarray facility for the analysis of the cancer-invasion process using Ovarian-cancer as a model of aggressive disease progression where we have evidenced a relevant class partition including elements of FGF2 pathway (DeCecco et al Ms in preparation)

(3) use of siRNA to dissect cancer-paths by combining HT-functional assays and gene-expression profiling as read-out.

• Henderson C, Mizzau M., Paroni G., Maestro R., Schneider C., Brancolini C. Role of caspases, Bid and p53 in the apoptotic response triggered by Histone Deacetylase Inhibitors TSA and SAHA. J. Biol. Chem January 29 2003
• Benetti R, Del Sal G, Monte M, Paroni G, Brancolini C, Schneider C. The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis. EMBO J. 200120(11):2702-14
• Goruppi S, Chiaruttini C, Ruaro ME, Varnum B, Schneider C. Gas6 induces growth, beta-catenin stabilization, and T-cell factor transcriptional activation in contact-inhibited C57 mammary cells Mol. Cel Biol 21: 902-15. 2001
• Demarchi F, Verardo R, Varnum B, Brancolini C, Schneider C. Gas6 anti-apoptotic signaling requires NF-kappa B activation. J Biol Chem. 24; 31738-44 2001
• Carninci P., Kvam C., Kitamura A., Ohsumi T.,, Okazaki Y., Itoh M., Kamiya M., Shibata K., Sasaki N., Izawa, M., Muramatsu M., Hayashizaki Y., and Schneider C. "High-efficiency full-length cDNA cloning by biotinylated CAP trapper". Genomics, Vol. 37: 327-336, 1996
• Goruppi S, Bonventre JV, Kyriakis JM. Signaling pathways and late-onset gene induction associated with renal mesangial cell hypertrophy. EMBO J. 15 5427-36 2002
• Benetti R, Del Sal G, Monte M, Paroni G, Brancolini C, Schneider C. The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis. EMBO J. 200120(11):2702-14
• Goruppi S, Chiaruttini C, Ruaro ME, Varnum B, Schneider C. Gas6 induces growth, beta-catenin stabilization, and T-cell factor transcriptional activation in contact-inhibited C57 mammary cells Mol. Cel Biol 21: 902-15. 2001
• Demarchi F, Verardo R, Varnum B, Brancolini C, Schneider C. Gas6 anti-apoptotic signaling requires NF-kappa B activation. J Biol Chem. 24; 31738-44 2001
• Carninci P., Kvam C., Kitamura A., Ohsumi T., Okazaki Y., Itoh M., Kamiya M., Shibata K., Sasaki N., Izawa M., Muramatsu M., Hayashizaki Y., and Schneider C. "High-efficiency full-length cDNA cloning by biotinylated CAP trapper". Genomics, Vol. 37: 327-336, 1996