Bryan P. Toole, Ph.D.
Professor
Member of Hollings Cancer Center

Room 620, Basic Science Building
Office: (843) 792-7004

Email: toolebp@musc.edu

Education:

BSc Biochemistry/Chemistry Univ Melbourne (Australia), 1962
MSc Biochemistry Monash (Australia), 1965
PhD Biochemistry Monash (Australia), 1968

Research Interests:

Our research addresses cell-cell and cell-extracellular matrix interactions in tumor growth and metastasis. In particular we study the molecular and cellular functions of hyaluronan (an extracellular and cell surface polysaccharide), CD44 and LYVE-1 (receptors for hyaluronan), and emmprin (CD147) (a cell surface glycoprotein that regulates production of hyaluronan and of matrix metalloproteinases).
Our current major focuses in the laboratory are:

1. The signaling mechanisms underlying the transforming effects of hyaluronan-CD44/LYVE1-emmprin interactions, especially the acquisition of malignant and chemoresistant properties.
2. The role of emmprin in invasiveness, especially formation of invadopodia.
3. The role of hyaluronan, CD44 and emmprin in the properties of cancer stem-like cells.
4. Molecular manipulations that block the functions of hyaluronan and emmprin in cancer.
5. Translation of our findings to the clinic, especially the use of small hyaluronan oligosaccharides as chemosensitizing agents for ovarian carcinoma, glioma, and AIDS-associated cancers.

For more on hyaluronan: http://www.glycoforum.gr.jp/science/hyaluronan/hyaluronanE.html

Recent Publications:

1. Gilg, A.G., Tye, S.L., Tolliver, L.B., Wheeler, W.G., Visconti, R.P., Duncan, J.D., Kostova, F.V., Bolds, L.N., Toole, B.P., and Maria, B.L. Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors. Clin. Cancer Res. 14:1804-1813, 2008.
2. Slomiany, M.G., Grass, G.D., Robertson, A.D., Yang, X., Maria, B.L., Beeson, C.C. and Toole, B.P.: Emmprin, hyaluronan and CD44 regulate lactate efflux and membrane localization of monocarboxylate transporters in human breast carcinoma cells. Cancer Res. 69:1293-301, 2009.
3. Slomiany, M.G., Dai, L., Bomar, P.A., Knackstedt, T.J., Kranc, D.A., Tolliver, L.B., Maria, B.L. and Toole, B.P.: Abrogating Drug Resistance in Malignant Peripheral Nerve Sheath Tumors by Disrupting Hyaluronan-CD44 Interactions with Small Hyaluronan Oligosaccharides. Cancer Res. 69: 4992-8, 2009.
4. Matsumoto, K., Li, Y., Jakuba, C., Sugiyama, Y., Sayo, T., Okuno, M., Dealy, C.N., Toole, B.P., Takeda, J., Yamaguchi, Y., and Kosher, R.A.: Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb. Development, 136:2825-35, 2009.
5. Slomiany, M.G., Dai, L., Tolliver, L.B., Grass, G.D. Zeng, Y. and Toole, B.P.: Inhibition of functional hyaluronan-CD44 interactions in CD133-positive primary human ovarian carcinoma cells by small hyaluronan oligosaccharides. Clin. Cancer Res. 15: 7593-7601, 2009.
6. Qin, Z., Dai, L., Slomiany, M.G., Toole, B.P., and Parsons, C.: Direct activation of emmprin and associated pathogenesis by an oncogenic herpesvirus. Cancer Res. 70: 3884-9, 2010.
7. Qin, Z., Dai, L., Bratoeva, M., Slomiany, M.G., Toole, B.P., and Parsons, C.:  Cooperative roles for emmprin and LYVE-1 in the regulation of chemoresistance for Primary Effusion Lymphoma. Leukemia, 25, 1598–1609, 2011.
8. Harten, I.A., Zahr, R.S., Lemire, J.M., Machan, J.T., Moses, M.A., Doiron, R.J., Curatolo, A.S., Rothman, F.G., Wight, T.N., Toole, B.P. and Gordon, L.B. Age-Dependent Loss of MMP-3 in Hutchinson-Gilford Progeria Syndrome. J Gerontol A Biol Sci Med Sci. 66:1201-7, 2011.
9. Dai, L., Bratoeva, M., Toole, B.P., Qin, Z., and Parsons, C. KSHV activation of VEGF secretion and invasion for endothelial cells is mediated through viral upregulation of emmprin-induced signal transduction. Int. J. Cancer. In press
10. Grass, G.D., Bratoeva, M., and Toole, B.P. Regulation of Invadopodia Formation and Activity by CD147. J. Cell Sci.: In press.

Recent Review:

Toole, B.P.: Hyaluronan-CD44 interactions in cancer: Paradoxes and possibilities. Clin. Cancer Res. 15: 7462-8, 2009