Charles A. O'Brien, Ph.D.

Professor of Medicine

Ph.D., University of Oklahoma Health Science Center

Research Interests:

The major goal my laboratory is to identify the molecular mechanisms that link the formation of osteoclasts to cells of the osteoblastic lineage. To this end we have cloned and characterized the gene promoter for RANKL, a cell surface protein expressed in stromal/osteoblastic cells that is absolutely required for osteoclast formation. We are currently identifying the signaling pathways and molecular mechanisms that regulate the expression of this gene in response to osteoclastogenic agents such as parathyroid hormone, the active form of vitamin D3, and cytokines.

Selected Publications:

Almeida M, Han L, O'Brien CA, Kousteni S, Manolagas SC. Classical Genotropic Versus Kinase-Initiated Regulation of Gene Transcription by the Estrogen Receptor {Alpha}. Endocrinology 147(4):1986-1996. 2006. [PM:16384865]*

Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL. Chronic Elevation of Parathyroid Hormone in Mice Reduces Expression of Sclerostin by Osteocytes: a Novel Mechanism for Hormonal Control of Osteoblastogenesis. Endocrinology 146(11):4577-4583. 2005. [PM:16081646]*

O'Brien CA, Jilka RL, Fu Q, Stewart S, Weinstein RS, Manolagas SC. IL-6 Is Not Required for Parathyroid Hormone Stimulation of RANKL Expression, Osteoclast Formation, and Bone Loss in Mice. Am J Physiol Endocrinol Metab 289(5):E784-E793. 2005 . [PM:15956054]*

O'Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS. Glucocorticoids Act Directly on Osteoblasts and Osteocytes to Induce Their Apoptosis and Reduce Bone Formation and Strength. Endocrinology 145(4):1835-1841. 2004. [PM:14691012]*

Bellido T, Ali AA, Plotkin LI, Fu Q, Gubrij I, Roberson PK, Weinstein RS, O'Brien CA, Manolagas SC, Jilka RL. Proteasomal Degradation of Runx2 Shortens Parathyroid Hormone-Induced Anti-Apoptotic Signaling in Osteoblasts. A Putative Explanation for Why Intermittent Administration Is Needed for Bone Anabolism. J Biol Chem 278(50):50259-50272. 2003. [PM:14523023]*

Kousteni S, Chen JR, Bellido T, Han L, Ali AA, O'Brien CA, Plotkin L, Fu Q, Mancino AT, Wen Y, Vertino AM, Powers CC, Stewart SA, Ebert R, Parfitt AM, Weinstein RS, Jilka RL, Manolagas SC. Reversal of Bone Loss in Mice by Nongenotropic Signaling of Sex Steroids. Science 298(5594):843-846. 2002. [PM:12399595]*

Fu Q, Jilka RL, Manolagas SC, O'Brien CA. Parathyroid Hormone Stimulates Receptor Activator of NFkappa B Ligand and Inhibits Osteoprotegerin Expression Via Protein Kinase A Activation of CAMP-Response Element-Binding Protein. J Biol Chem 277(50):48868-48875. 2002. [PM:12364326]*

O'Brien CA, Kern B, Gubrij I, Karsenty G, Manolagas SC. Cbfa1 Does Not Regulate RANKL Gene Activity in Stromal/Osteoblastic Cells. Bone 30(3):453-462. 2002. [PM:11882458]*

Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC. Nongenotropic, Sex-Nonspecific Signaling Through the Estrogen or Androgen Receptors: Dissociation From Transcriptional Activity. Cell 104(5):719-730. 2001. [PM:11257226]*

Additional publications listed on PubMed*