Ph.D. 2000 University of Rochester School of Medicine and Dentistry
Associate Dean for Clinical Affairs, URMC
Wehle Professor and Chair,
Department of Orthopaedics and Rehabilitation
Primary Appointment: Department of Orthopaedics
Center Affiliation: Center for Musculoskeletal Research
The O’Keefe laboratory is interested in both skeletal development and skeletal injury repair. We combine in vivo genetic mouse models with in vitro tissue culture and molecular biology techniques to better understand the role of specific genes in regulation of bone and joint development, the onset of osteoarthritis, fracture repair, and tendon healing. Additionally, we are interested in the role of mesenchymal stem cells, multipotent progenitor cells capable of differentiating into bone, cartilage, muscle and fat, in each of these processes. Furthermore, we are interested in identifying those factors involved in the maintenance of mesenchymal stem cell populations and regulation of mesenchymal stem cell differentiation.
Current projects in the lab include studies aimed at defining the roles of Bmp/Tak1 and Wnt/β-catenin signaling during both skeletal development and the onset of osteoarthritis. We are also investigating the role of Cox-2/PGE2 signaling during fracture repair and bone homeostasis. Finally, we are assessing the roles of canonical and non-canonical TGF-β signaling during both tendon development and tendon injury repair. Each of these projects is aimed at better understanding the molecular events involved in skeletal development or disease and will ultimately aid in the identification of novel therapeutic targets for the treatment of musculoskeletal disorders.
Tendon Development and Injury Repair
Mesenchymal Stem Cell Self-renewal and Differentiation
Zhang M, Ho H-C, Sheu T-J, Breyer MD, Flick LM, Jonason JH, Awad HA, Schwarz EM, O’Keefe RJ. EP1-/- mice have enhanced osteoblast differentiation and accelerated fracture repair. J Bone Miner Res. 2011; 26:792-802.
Katzel EB, Wolenski M, Loiselle AE, Basile P, Flick LM, Langstein HN, Hilton MJ, Awad HA, Hammert WC, O'Keefe RJ. Impact of Smad3 loss of function on scarring and adhesion formation during tendon healing. J Orthop Res. 2011; 29:684-93.
Li T-F, Gao L, Sheu T-J, Sampson ER, Flick LM, Konttinen YT, Chen D, Schwarz EM, Zuscik MJ, Jonason JH, O’Keefe RJ. Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor beta-activated kinase 1/activating transcription factor 2 signaling: A potential clinical implication for osteoarthritis. Arthritis Rheum. 2010; 62:2359-69.
Gunnell LM, Jonason JH, Loiselle AE, Kohn A, Schwarz EM, Hilton MJ, O'Keefe RJ. TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways. J Bone Miner Res. 2010; 25:1784-97.
Dao DY, Yang X, Flick LM, Chen D, Hilton MJ, O'Keefe RJ. Axin2 regulates chondrocyte maturation and axial skeletal development. J Orthop Res. 2010; 28:89-95.
Tsutsumi R, Xie C, Wei X, Zhang M, Zhang X, Flick LM, Schwarz EM, O'Keefe RJ. PGE2 signaling through the EP4 receptor on fibroblasts upregulates RANKL and stimulates osteolysis. J Bone Miner Res. 2009; 24:1753-62.
Loiselle AE, Bragdon GA, Jacobson JA, Hasslund S, Cortes ZE, Schwarz EM, Mitten DJ, Awad HA, O'Keefe RJ. Remodeling of murine intrasynovial tendon adhesions following injury: MMP and neotendon gene expression. J Orthop Res. 2009; 27:833-40.
Clark CA, Li TF, Kim KO, Drissi H, Zuscik MJ, Zhang X, O'Keefe RJ. Prostaglandin E2 inhibits BMP signaling and delays chondrocyte maturation. J Orthop Res. 2009; 29:785-92.
Naik AA, Xie C, Zuscik MJ, Kingsley P, Schwarz EM, Awad H, Guldberg R, Drissi H, Puzas JE, Boyce B, Zhang X, O'Keefe RJ. Reduced COX-2 expression in aged mice is associated with impaired fracture healing. 2009; 24:251-64.
Chen M, Zhu M, Awad H, Li TF, Sheu TJ, Boyce BF, Chen D, O'Keefe RJ. Inhibition of beta-catenin signaling causes defects in postnatal cartilage development. J Cell Sci. 2008; 121:1455-65.
Graduate Program Affiliations