Mr. William Gunn |
|
Tulane University School of Medicine Molecular and Cellular Biology Program Graduate StudentAppointed: 2002 |
Mailing AddressTulane University Center for Gene Therapy 1430 Tulane Avenue SL-99 New Orleans, Louisiana 70112United States | Contact InformationWilliam.Gunn@gmail.com http://www.biomedicalsciences.tulane.edu/student_detail.php?recordID=47 |
Qualifications
B.S., University of Southern Mississippi, Molecular Biology, 2001.
Expertise and Research Interests
Mesenchymal Stem Cell Biology
Tissue Repair
Wnt Signaling
Bone Biology
Multiple Myeloma
Stereology
Data Mining
Statistics
Bioinformatics
Tissue Repair
Wnt Signaling
Bone Biology
Multiple Myeloma
Stereology
Data Mining
Statistics
Bioinformatics
Other Expertise
As part of my graduate research, I have participated in research showing:
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.
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.
Future Research
* Show that osteoclasts are upregulated while osteoblasts are deficient in an animal model of multiple myeloma.
* 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.
* 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.
Industrial Relevance
Clinical Applications of Mesenchymal Stem Cells
Drug Screening
Drug Screening
Keywords
COS Keywords:
Cell Biology, Developmental Biology, Gene Regulation, Gene Therapy, Genetics, Molecular Biology, Molecular Genetics, Structural Biology, Transcription.Additional Terms:
Molecular Biology.Memberships
International Society for Cellular Therapy
Funding Received
- Louisiana Board of Regents: Fellowship, $18,000, 2002 to 2006.
Publications
- Carl Gregory, Angela Green, Narae Lee, Ashwin Rao, William Gunn (2006) The promise of canonical Wnt signaling modulators in enhancing bone repair., Drug News & Perspectives, 19 (8), 445-52
- William Gunn, Adam Conley, Lisa Deininger, Scott Olson, Darwin Prockop, Carl Gregory (2006) 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, 24 (4), 986-91
- Gregory CA, Gunn WG, Reyes E, Smolarz AJ, Munoz J, Spees JL, Prockop DJ, How Wnt Signaling Affects Bone Repair By Mesenchymal Stem Cells From the Bone., Annals of the New York Academy of Sciences, http://www.annalsnyas.org/, New York Academy of Sciences, 1049, 97-106, May 2005
- Gregory CA, Perry AS, Reyes E, Conley A, Gunn WG, Prockop DJ, Dkk-1-derived Synthetic Peptides and Lithium Chloride for the Control And
Recovery of Adult Stem Cells From Bone Marrow., The Journal of Biological Chemistry, 280(3), 2309-23, Jan 2005
- Gregory CA, Gunn WG, Peister A, Prockop DJ, An Alizarin Red-based Assay of Mineralization By Adherent Cells In
Culture: Comparison With Cetylpyridinium Chloride Extraction., Analytical Biochemistry, 329(1), 77-84, Jun 2004
Profile Details
Last Updated: 10/18/2007
COS Expertise ID #969352
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