John Di Guglielmo
PH.D. McGill University
B.Sc. McGill University
Office: Medical Sciences Building 228
p. 519.661.2111 x. 80042
See Publications by John Di Guglielmo on PubMed
The TGFβ superfamily regulates many cellular functions and its deregulation leads to human diseases such as cancer of the breast, colon, pancreas and lung. In normal lung epithelium, TGFβ is a tumor suppressor but in cancer cells it switches roles and promotes lung cancer metastasis. The underlying mechanisms by which TGFβ promotes this switch remain unclear and are under investigation in our laboratory. One area of our research program focuses on the relationship between TGFβ receptor trafficking and signal transduction. We use fluorescent reporter molecules and immunofluorescence microscopy to follow receptor endocytosis in live cells and various molecular and cell biological techniques to assess receptor signal transduction. A second area of our research involves the regulation of normal and cancer cell migration by synthetic triterpenoids. Triterpenoids are naturally occurring compounds that alter TGFβ signal transduction and have been found to inhibit tumor metastasis in animal models. We are investigating the cellular mechanisms that these compounds use to block metastasis using various in vitro cell migration and molecular approaches.
Ogunjimi A., Pece-Barbara N., Kavsak P., Le Roy C., Di Guglielmo G.M., Rasmussen R., Sicheri F. and Wrana J.L. (2005). Smad7 potentiates Smurf2 ubiquitin ligase activity by anchoring E2 to the HECT domain. Mol. Cell 19: 1-12.
Pece-Barbara N., Vera S., Kathirkamathamby K., Liebner S., Di Guglielmo G.M., Dejana E., Wrana J.L., Letarte M.. (2005). Endoglin null endothelial cells proliferate faster and are more responsive to TGFbeta1 with higher affinity receptors and an activated ALK1 pathway. J. Biol. Chem. 280: 27800-27808.
Partridge E.A., Le Roy C., Di Guglielmo G.M., Pawling J., Cheung P., Granovsky M., Nabi I.R., Wrana J.L. and Dennis J.W. (2004). Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science 306:120-124.
Swallow C.J., Partridge E.A., Macmillan J.C., Tajirian T., Di Guglielmo G.M., Hay K., Szweras M., Jahnen-Dechent W., Wrana J.L., Redston M., Gallinger S., Dennis J.W.. (2004). Alpha2HS-glycoprotein, an antagonist of transforming growth factor beta in vivo, inhibits intestinal tumor progression. Cancer Res. 64: 6402-6409.
Di Guglielmo, G.M.*, Le Roy, C.*, Davison, A. F. and Wrana, J. L. (2003). Distinct endocytic pathways regulate TGFbeta receptor signaling and turnover. Nature Cell Biol. 5; 410-421.
To, C., Kulkarni, S., Pawson A.J., Honda T., Gribble G.W., Sporn M.B., Wrana J.L and Di Guglielmo, G.M. (2008) The synthetic triterpenoid CDDO-Im extends TGFβ receptor signaling by disrupting the polarity complex and vesicular traffic. J. Biol. Chem. 283: 11700-11713