Bryan P. Toole, Ph.D.
Member of Hollings Cancer Center
Room 620, Basic Science Building
Office: (843) 792-7004
BSc Biochemistry/Chemistry Univ Melbourne (Australia), 1962
MSc Biochemistry Monash (Australia), 1965
PhD Biochemistry Monash (Australia), 1968
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:
- The signaling mechanisms underlying the transforming effects of hyaluronan-CD44/LYVE1-emmprin interactions, especially the acquisition of malignant and chemoresistant properties.
- The role of emmprin in invasiveness, especially formation of invadopodia.
- The role of hyaluronan, CD44 and emmprin in the properties of cancer stem-like cells.
- Molecular manipulations that block the functions of hyaluronan and emmprin in cancer.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- Grass, G.D., Bratoeva, M., and Toole, B.P. Regulation of Invadopodia Formation and Activity by CD147. J. Cell Sci.: In press.
Toole, B.P.: Hyaluronan-CD44 interactions in cancer: Paradoxes and possibilities. Clin. Cancer Res. 15: 7462-8, 2009