Skin • tissue fibrosis • scleroderma • cartilage • osteoarthritis • TGF-beta
My research focuses on understanding the role of TGF-beta signaling in wound healing and scarring in the skin, and in the maintenance and repair of cartilage. In the cartilage, our studies center on understanding how the functional interplay between TGF-beta receptors and co-receptors regulates chondrocyte phenotype and function, in healthy and osteoarthritic cartilage. Our research on skin focuses on TGF-beta co-receptors as regulators of TGF-beta signaling in skin cells. We have recently shown that CD109, a novel TGF-beta co-receptor that we have identified in skin cells, inhibits TGF-beta signaling and displays potent anti-fibrotic properties in vitro and in vivo. One of our major objectives is to develop CD109-based peptides as TGF-b antagonists and anti-fibrotic agents for the treatment of pathological conditions such as hypertrophic scarring and scleroderma. Research in my laboratory is funded by the Canadian Institute for Health Research (CIHR), NSERC and United States Department of Defense.
Vorstenbosch J, Gallant-Behm C, Trzeciak A, Roy S, Mustoe T, Philip A: Transgenic mice overexpressing CD109 in the epidermis display decreased inflammation and granulation tissue and improved collagen architecture during wound healing. Wound repair and regeneration 2013, 21(2):235-246.
Vorstenbosch J, Al-Ajmi H, Winocour S, Trzeciak A, Lessard L, Philip A: CD109 overexpression ameliorates skin fibrosis in a bleomycin-induced mouse model of scleroderma. Arthritis and rheumatism 2013, 65(5):1378-1383.
Man XY, Finnson KW, Baron M, Philip A: CD109, a TGF-b co-receptor, attenuates extracellular matrix production in scleroderma skin fibroblasts. Arthritis research & therapy 2012, 14(3):R144.
Bizet AA, Liu K, Tran-Khanh N, Saksena A, Vorstenbosch J, Finnson KW, Buschmann MD, Philip A: The TGF-b co-receptor, CD109, promotes internalization and degradation of TGF-b receptors. Biochim Biophys Acta: Molecular Cell Research 2011, 1813(5):742-753.
Finnson KW, Parker WL, Chi Y, Hoemann C, Goldring MB, Antoniou J, Philip A: Endoglin differentially regulates TGF-b-induced Smad2/3 and Smad1/5 signalling and its expression correlates with extracellular matrix production and cellular differentiation state in human chondrocytes. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society 2010, 18(11):1518-1527.