Curriculum Vitae for William Gunn
Contact:
William Gunn
Tulane University Center for Gene Therapy
1430 Tulane Ave. SL-99
New Orleans, LA 70112
wgunn@tulane.edu
Education:
B.S., University of Southern Mississippi, Molecular Biology, 2001
Tulane University, School of Medicine, Molecular and Cellular Biology Program, Class of 2002
William Gunn is a senior graduate student at the Tulane Center for Gene Therapy, where he is completing a dissertation is entitled "The Role of Human Multipotent Mesenchymal Stromal Cells in the Repair of Bone."
Research Interests and Expertise:
Mesenchymal Stem Cell Biology
Tissue Repair
Wnt Signaling
Bone Biology
Multiple Myeloma
Stereology
Data Mining
Statistics
Bioinformatics
Publications
- Gregory,C., Green,A., Lee,N., Rao,A. & Gunn,W. The promise of canonical Wnt signaling modulators in enhancing bone repair. Drug news & perspectives 19, 445-452 (2006).
- Gunn,W. et al. A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: a potential role in the development of lytic bone disease and tumor progression in multiple myeloma. Stem cells (Dayton, Ohio) 24, 986-991 (2006).
- Gregory,C. et al. Dkk-1-derived Synthetic Peptides and Lithium Chloride for the Control and Recovery of Adult Stem Cells from Bone Marrow. Journal of Biological Chemistry 280, 2309-2323 (2005).
- Gregory,C. et al. How Wnt Signaling Affects Bone Repair by Mesenchymal Stem Cells from the Bone Marrow. Annals of the New York Academy of Sciences 1049, 97-106 (2005).
- Gregory,C., Gunn,W., Peister,A. & Prockop,D. An Alizarin red-based assay of mineralization by adherent cells in culture: comparison with cetylpyridinium chloride extraction. Anal Biochem 329, 77-84 (2004).
An up-to-date list of publications can be found here.
Funding Received:
Louisiana Board of Regents: Fellowship, $18000, from 2002 to 2006
Professional Society Memberships:
International Society for Cellular Therapy
Networking
Connotea
Nature Network
Community of Science
Research Summary:
MSCs contribute to bone repair by proliferating under the influence of Dkk1 and then undergoing osteogenesis to effect remodeling at the site of injury.
- Dkk1 is produced by MSCs at low density.
- IL6 is produced by undifferentiated, dividing MSCs.
- MSCs express LRP6 and Kremen1 receptors.
- Radiolabeled Dkk1 is taken up by MSCs.
- Recombinant Dkk1 promote proliferation of MSCs and blocks differentiation as measured by calcium accumulation assayed by either Alizarin Red or arsenazo III, or by expression of membrane-associated alkaline phosphatase.
- Inhibition of Dkk1’s effects on MSCs with a Wnt agonist allows MSCs to continue to differentiate in the presence of Dkk1.
Dkk1 is secreted by myeloma cells, which produce osteolytic lesions that are resistant to remodeling.
- The lesions occur due to an osteoblast deficit.
- Osteoclasts are normal, and more active or numerous than in normal patients.
- The IL6 that is secreted by MSCs is a strong growth factor for myeloma cells.MSCs from myeloma patients are significantly different from normal MSCS.
- Inhibition of the effects of Dkk1 with a small molecule, well tolerated, Wnt agonist may prevent the changes to MSCs brought about by multiple myeloma, and may make lesions susceptible to remodeling again.
- An animal model for multiple myeloma, wherein human myeloma cells are administered to a immundeficient mouse, causes bone resorption and tumor formation.
Experiments in Progress
- Show that osteoclasts are upregulated while osteoblasts are deficient in the animal model.
- Show that Dkk1 is produced by the tumors in vivo, and is correlated with the magnitude of the defect.
- Show that MSCs derived from these animals are different in a similar fashion to the MSCs derived from myeloma patients.
- Show that I can treat the animals in this model with the Wnt agonist and reduce the size of tumors and incidence of osteolytic lesions.