Members of the Bone Morphogenetic Protein (BMP) subgroup of TGF�-related molecules have been implicated in many key signalling events in vertebrates and invertebrates. We are using the mouse as a model organism to study the roles of these regulatory factors during vertebrate development, focusing on skeletal tissues. Our approach is to take advantage of the genetic capabilities the mouse system offers, including transgenic and gene targeting technologies. We are also using organ and cell culture strategies.
We are also investigating the functions of the CCN family of matricellular proteins in various organs. We have generated gain and loss-of function models for 4 of the six family members and have identified essential functions in chondrogenesis, angiogenesis, and branching morphogenesis in the mammary and salivary glands. We have found that many of these effects appear to be mediated by the ability of CCN proteins to engage integrins.
Jiang J, Hu Z, Lyons KM, "Design and Analysis of CCN Gene Activity Using CCN Knockout Mice Containing LacZ Reporters", In: Methods Mol. Biol 489: 325-345 (2017). [link]
Pan H, Zhang H, Abraham P, Komatsu Y, Lyons K, Kaartinen V, Mishina Y., "BMPR1A is a major type I BMP receptor for BMP-Smad signaling in skull development", Dev. Biol pii: S0012-1606(16)3: 1-11 (2017). [link]
Falke LL, Leeuwis JW, Lyons KM, Mummery CL, Nguyen TQ, Goldschmeding R., "CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy", . J Cell Commun Signal 11: 39-48 (2017). [link]
Zhang Y, Huang H, Zhao G, Yokoyama T, Vega H, Huang Y, Sood R, Bishop K, Maduro V, Accardi J, Toro C, Boerkoel CF, Lyons K, Gahl WA, Duan X, Malicdan MC, Lin S., "ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13", PLoS Genet 13: 1-15 (2017). [link]
Nishida T, Kubota S, Aoyama E, Yamanaka N, Lyons KM, Takigawa M., "Low-intensity pulsed ultrasound (LIPUS) treatment of cultured chondrocytes stimulates production of CCN family protein 2 (CCN2), a protein involved in the regeneration of articular cartilage: Mechanism underlying this stimulation", Osteoarthritis Cart 25: 759-769 (2017). [link]
Burga A, Wang W, Ben-David E, Wolf PC, Ramey AM, Verdugo C, Lyons K, Parker PG, Kruglyak L, "A genetic signature of the evolution of loss of flight in the Galapagos Cormorant", Science 356: 921-928 (2017). [link]
Jiang J, Leong NL, Khalique U, Phan TM, Lyons KM, Luck JV., "Connective tissue growth factor (CTGF/CCN2) in haemophilic arthropathy and arthrofibrosis: a histological analysis", Haemophilia doi: 10.1111/hae.130: 527-536 (2016). [link]
Perbal B, Lau L, Lyons K, Kubota S, Yeger H, Fisher G., "Report on the 8th International Workshop on the CCN Family of Genes", J Cell Commun Signal 10: 77-86 (2016). [link]
Shi C, Iura A, Terajima M, Liu F, Lyons K, Pan H, Zhang H, Yamauchi M, Mishina Y, Sun H., "Deletion of BMP receptor type IB decreased bone mass in association with compromised osteoblastic differentiation of bone marrow mesenchymal progenitors", Sci Rep 6: 1-13 (2016). [link]
Zieba J, Forlenza KN, Khatra JS, Sarukhanov A, Duran I, Rigueur D, Lyons KM, Cohn DH, Merrill AE, Krakow D., "TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions", PLoS Genet 12 (e1005936): 1-22 (2016). [link]
Murase Y, Hattori T, Aoyama E, Nishida T, Maeda-Uematsu A, Kawaki H, Lyons KM, Sasaki A, Takigawa M, Kubota S., "Role of CCN2 in Amino Acid Metabolism of Chondrocytes", J Cell Biochem 117: 927-937 (2016). [link]
Mangiavini L, Merceron C, Araldi E, Khatri R, Gerard-O'Riley R, Wilson TL, Sandusky G, Abadie J, Lyons KM, Giaccia AJ, Schipani E., "Fibrosis and hypoxia-inducible factor-1α-dependent tumors of the soft tissue on loss of von Hippel-Lindau in mesenchymal progenitors", Am J Pathol 185: 3090-3101 (2015). [link]
James AW, Shen J, Zhang X, Asatrian G, Goyal R, Kwak JH, Jiang L, Bengs B, Culiat CT, Turner AS, Seim Iii HB, Wu BM, Lyons K, Adams JS, Ting K, Soo C., "NELL-1 in the treatment of osteoporotic bone loss", Nat Commun 6: 7362-7375 (2015). [link]
Maeda A, Ono M, Holmbeck K, Li L, Kilts TM, Kram V, Noonan ML, Yoshioka Y, McNerny EM, Tantillo MA, Kohn DH, Lyons KM, Robey PG, Young MF., "WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone Turnover and Wnt Signaling", 290: 14004-14018 (2015).
Rigueur D, Brugger S, Anbarchian T, Kim JK, Lee Y, Lyons KM., "The type I BMP receptor ACVR1/ALK1 is required for chondrogenesis during development", J Bone Miner Res 30: 733-741 (2015).