Developmental & Molecular Pathways

The Developmental and Molecular Pathways (DMP) Group strives to better understand the molecular anatomy of disease by defining key developmental genetic pathways and druggable nodes in the “Wnt,” “TGF-beta,” “Hedgehog,” “Notch,” and “PI3K” pathways. Disruptions in these signaling networks can lead to many diseases. For example, the Wnt pathway is involved in cancer and bone loss, and the Hedgehog pathway is implicated in skin cancer, brain cancer and the regeneration of tissue.

The goal of DMP is to identify and validate novel targets (druggable nodes in the pathways) with a focus on: tumor biology, stem cell biology (regenerative medicine), neuro/muscular degeneration, human genetics and epigenetics, and immunology.

DMP's core capabilities in pathway analysis for target identification/validation include: genomics, proteomics, model organisms, screening, and computational biology.

 

Selected publications

Oxysterols direct immune cell migration via EBI2. Hannedouche,S., Zhang,J., Yi,T., Shen,W., Nguyen,D., Pereira,J.P., Guerini,D., Baumgarten,B.U., Roggo,S., Wen,B., Knochenmuss,R., Noel,S., Gessier,F., Kelly,L.M., Vanek,M., Laurent,S., Preuss,I., Miault,C., Christen,I., Karuna,R., Li,W., Koo,D.I., Suply,T., Schmedt,C., Peters,E.C., Falchetto,R., Katopodis,A., Spanka,C., Roy,M.O., Detheux,M., Chen,Y.A., Schultz,P.G., Cho,C.Y., Seuwen,K., Cyster,J.G., and Sailer,A.W. (2011). Nature 475, 524-527.

RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Zhang,Y., Liu,S., Mickanin,C., Feng,Y., Charlat,O., Michaud,G.A., Schirle,M., Shi,X., Hild,M., Bauer,A., Myer,V.E., Finan,P.M., Porter,J.A., Huang,S.M., and Cong,F. (2011). Nat. Cell Biol 13, 623-629.

Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Huang,S.M., Mishina,Y.M., Liu,S., Cheung,A., Stegmeier,F., Michaud,G.A., Charlat,O., Wiellette,E., Zhang,Y., Wiessner,S., Hild,M., Shi,X., Wilson,C.J., Mickanin,C., Myer,V., Fazal,A., Tomlinson,R., Serluca,F., Shao,W., Cheng,H., Shultz,M., Rau,C., Schirle,M., Schlegl,J., Ghidelli,S., Fawell,S., Lu,C., Curtis,D., Kirschner,M.W., Lengauer,C., Finan,P.M., Tallarico,J.A., Bouwmeester,T., Porter,J.A., Bauer,A., and Cong,F. (2009). Nature 461, 614-620.

Pharmaceuticals: A new grammar for drug discovery. Fishman M.C.; Porter J.A.. Nature (22 September 2005); 437: 491-493.