Carl Gregory
Assistant Professor
Department
5701 Airport Road, Module C
Temple,
Texas 76502
Phone: 254-771-6816
Fax: 254-771-6839
Email: user@component.tamhsc.edu
Education and Post-Graduate Training
Research Interests
General Biology of MSCs:
Mesenchymal stem cells (MSCs) are purified from bone marrow based on their ability to adhere to plastic. The resulting cultures are therefore heterogeneous, contaminated with small numbers of differentiated cells such as fibroblasts and osteoblasts. As MSCs are further expanded, they gradually lose their plasticity and proliferative activity. In some cases, therefore, the quality and purity of MSC preparations can seriously influence their efficacy. Dr Gregory’s lab has been examining the biology of MSCs with a view to developing rapid molecular markers and tests for evaluating/purifying maximally efficacious cultures of MSCs. For example, the group has recently demonstrated leukemia inhibitory factor secretion is a robust predictor of differentiation potential.
MSCs and bone healing:
The group specializes in bone repair by MSCs. Based on detailed characterization of the molecular mechanism of osteoblast differentiation by MSCs, a novel and effective bone regeneration strategy has been developed. This strategy, based on pharmaceutical conditioning of MSC cultures prior to administration in a specialized matrix, re-initiates bone formation in non-healing bone defects in mice. Further trials in large animals are planned.
Malignant bone disease:
Many tumors of the skeleton destroy bone tissue to facilitate their expansion and metastasis. Furthermore, the mechanisms by which some tumors inhibit the repair of host bone, often increase the aggressiveness of the tumor cells themselves. The Gregory group contributed to the discovery that Dkk-1, a secreted inhibitor of the Wnt pathway inhibits the repair of bone by MSCs. When Dkk-1 is over expressed by osteosarcoma cells, they are more effective in destroying and infiltrating bone. The tumor cells themselves also respond in an autocrine manner to Dkk-1 by becoming highly primitive and highly proliferative, thus becoming a highly aggressive tumor. The group is currently examining the effects of various small molecules and immunological strategies for the safe and effective inhibition of Dkk-1 activity in bone tumors.
Selected Publications
Whitney M. J., Lee. A., Zeitouni, S., Tucker H. A., Jlostalo, J. and Gregory, C. A. (2008) "Leukemia inhibitory factor secretion is an indicator and predictor early progenitor status of marrow stromal cells from adult human bone marrow."Tiss. Eng. Epub ahead of print.
Lee, N., Smolarz, A. J., Olson, S., David, O., Reiser, J., Kutner, R, Daw, N. C., Prockop, D. J., Horwitz, E. M. and Gregory, C. A. (2007) "A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies." British J. Cancer. 97, 1552-1559.
Gregory, C. A., Reyes, E., Whitney, M. J. and Spees, J. L. (2006) "Enhanced engraftment of mesenchymal stem cells in a cutaneous wound model by culture in allogenic species specific serum and administration in fibrin constructs." Stem Cells. 24, 2232-2243.
Gunn, W. G., Conley, A., Deininger, L., Olson, S. D., Prockop, D. J. and Gregory, C. A. (2005) "A Crosstalk between Myeloma Cells and Marrow Stromal Cells Stimulates Production of DKK1 and IL-6: A Potential Role in the Development of Lytic Bone Disease and Tumor Progression in Multiple Myeloma." Stem Cells. 24, 986-991
Gregory C. A. Singh, H. Perry, A. S. and Prockop D. J. (2003) "Wnt signaling inhibitor Dkk-1 is required for re-entry into the cell cycle of human adult stem cells from bone marrow stroma (hMSCs)." J. Biol. Chem. 278, pp. 28067-28078.
