Dana Gaddy, Ph.D.
Professor
Ph.D., Baylor College of Medicine

Office: (501) 686-5918
Fax: (501) 686-8167
Email: gaddydana@uams.edu

1. The molecular and cellular bases for and the physiological roles of activin, inhibin, and bone morphogenetic protein (BMP) action on osteoblast and osteoclast differentiation during bone remodeling.  Using a multi-disciplinary approach to addressing these goals, in vitro analyses of osteoblast and osteoclast differentiation are coupled with analysis of bone phenotype.  In vivo models include transgenic mice with altered inhibin and activin action that are used to determine the role that these growth factors have on bone remodeling.  Finally, our human studies focus on determining if changes in inhibin levels in men and women are correlated with changes in bone turnover, bone mass, and bone quality.

2. Integral effects of disuse on the musculoskeletal system.  Using a rat model of limb disuse and exercise countermeasures, our approach is to determine the mechanisms of bone loss and coordinated muscle atrophy as well as the mechanisms of musculoskeletal restoration that may differ during aging (in collaboration with Drs. Larry Suva and Esther Dupont-Versteegden). We hope to determine the type and extent of reloading and/or exercise that is required to independently maintain and restore both bone and muscle during disuse. We have also adapted these studies to our mouse transgenic models to determine the impact of inhibin overexpression on musculoskeletal disuse.

3. Mechanisms of osteolytic metastatic bone disease.  In collaboration with Dr. Larry Suva, our goal is to determine the cascade of molecular events that are responsible for breast cancer cells homing to bone, growing in bone, and causing bone destruction (osteolysis).  Gene array technology and protein profiling are used to address these mechanisms for subsequent determination of the contribution of validated target molecules (eg. IL- 8) on osteoclast formation and function, and in a mouse model of tumor osteolysis.

Dr. Gaddy Lab Homepage

Link to BRIN

Representative Publications

Nicks, K.M., Perrien, D.S., N.S. Akel, L.J. Suva, and Gaddy, D. (2009) Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, Activin and Inhibin Molecular and Cellular Endocrinology. Mol Cell Endocrinol. 2009 Oct 30;310(1-2):11-20. Epub 2009 Jul 15.

Gaddy, D. (2008) Inhibin and the Regulation of Bone Mass Osteoporosis Reports (2008) 6:51–56

Perrien, D.S.  N.S. Akel, R.A. Skinner, F.L. Swain, P.K. Edwards, A.A., Carver, T.M. Pierson, L.J. Suva, and Gaddy, D. (2007)  Inhibin A is a Novel Stimulator of Bone Mass and Strength. Endocrinology Apr;148(4):1654-65. (Epub Dec 28, 2006)

T.J. Martin and D. Gaddy (2006) Bone Loss Goes Beyond Estrogen Nature Medicine Jun;12(6):612-3.

D.S. Perrien, S.E. Bledsoe, Achenbach, S.J., Khosla, S., and Gaddy, D. (2006) Inhibin Regulation of Osteoblastogenesis and Osteoclastogenesis and Correlation with Markers of Bone Turnover and Bone Mineral Density Across the Menopause Transition. J. Clin. Endo. Metab.  May;91(5):1848-54. (Epub ahead of print Jan 31).

D. S. Perrien, N. S. Akel, R. A. Skinner, E.E. Dupont-Versteegden, L. J. Suva, and D. Gaddy. (2006) Aging Alters the Skeletal Response to Disuse in the Rat.  Am. J. Physiol. Regulatory and Integrative Biol. 292(2):R988-96. (Epub Oct 26, 2006)

E.E. Dupont-Versteegden, J.D. Fluckey, M. Knox, D. Gaddy, C.A. Peterson. (2006) The effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats. J Appl Physiol. Jul;101(1):202-12 (Epub ahead of print Apr 6).

L. J. Suva, D. Gaddy, D. S. Perrien, R.L. Thomas, and D.M. Findlay (2005). Regulation of Bone Mass by Mechanical Loading: Microarchitecture and Genetics. Current Osteoporosis Reports 2005, 3:46–51

M.S. Bendre, A.G. Margulies, B. Walser, N.S. Akel, S. Bhattacharrya, R.A. Skinner, F. Swain, V. Ramani, K. S. Mohammad, L.L. Wessner, A. Martinez, T.A. Guise, J. M. Chirgwin, D. Gaddy, and L.J. Suva (2005). Tumor-Derived Interleukin 8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-KB Ligand Pathway. 2005 Cancer Res; 65(23): 1-9

M.S. Bendre, D.C. Montague, T. Peery, N.S. Akel, D. Gaddy and L.J. Suva (2003) Interleukin-8 activation of osteoclastogenesis and bone resorption: A mechanism for the increased osteolysis of metastatic bone disease.  Bone 33 (28-37).

M.S. Bendre, D. Gaddy-Kurten, T. Mon-Foote, N.S. Akel, R.A. Skinner, R.W. Nicholas, and L.J. Suva (2002) Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo.  Cancer Research, 62:5571-5579.

J.D. Fluckey, E. Dupont-Versteegen, C.A. Peterson and D. Gaddy-Kurten. (2002) Resistance exercise training maintains musculoskeletal mass in rats under conditions of simulated microgravity.  Acta Scandanavica Physiologica,  176:1-8.

D. Gaddy-Kurten,  J.K. Coker, R.L. Jilka, and S.C. Manolagas. (2002) Inhibin suppresses and activin stimulates osteoblastogenesis and osteoclastogenesis in murine bone marrow cultures. Endocrinology 143:74-83.

Link to Dr. Gaddy-Kurten at PubMed

Link to Dr. Gaddy at PubMed

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