Ph.D., University of Illinois, Urbana-Champaign
Tel: (617) 552-3563
E-mail: thomas.seyfried@bc.edu
Lab Website: http://www2.bc.edu/~seyfridt
Fields of Interest
Gene-environmental interactions in epilepsy and brain cancer
Academic Profile
Our research program focuses on dietary therapies for epilepsy, brain cancer, and neurodegenerative lipid storage diseases. These therapies include caloric restriction, fasting, and the ketogenic diet. Our goal is to manage complex diseases through principles of metabolic control theory. This theory is based on the idea that compensatory or redundant brain metabolic pathways are capable of modifying the pathogenesis of complex diseases despite the continued presence of the genetic or environmental defects responsible for the disease. By shifting the brain metabolic environment, diet therapies can potentially mask or neutralize molecular pathology. The neurochemical and genetic mechanisms of these phenomena are under investigation in genetic animal models and include the processes of inflammation, programmed cell death, angiogenesis, and bioenergetics.
Representative Publications
Huysentruyt, L.C., Shelton, L.M., Seyfried, T.N. 2009. Influence of methotrexate and cisplatin on tumor progression and survival in the VM mouse model of systemic metastatic cancer. International Journal of Cancer. 2009, Jun 17. [Epub ahead of print]
Mantis, J.G., Fritz, C.L., Marsh, J., Heinrichs, S.C., Seyfried, T.N. 2009. Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets. Epilepsy & Behavior 15(2): 133–41.
Baek, R.C., Martin, D.R., Cox, N.R., Seyfried, T.N. 2009. Comparative analysis of brain lipids in mice, cats, and humans with Sandhoff disease. Lipids 44(3): 197–205.
Seyfried, T.N., Kiebish, M., Mukherjee, P., Marsh, J. 2008. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets. Epilepsia 49 (8): 114–6.
Marsh, J., Mukherjee, P., Seyfried, T.N. 2008. Akt-dependent proapoptotic effects of dietary restriction on late-stage management of a phosphatase and tensin homologue/tuberous sclerosis complex 2-deficient mouse astrocytoma. Clinical Cancer Research 14(23): 7751–62.
Kiebish, M.A., Han, X., Cheng, H., Chuang, J. H., and Seyfried, T. N. 2008. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. Journal of Lipid Research 49: 2545–2556.
Kiebish, M.A., Han, X., Cheng, H., Chuang, J.H., Seyfried, T. N. 2008. Brain mitochondrial lipid abnormalities in mice susceptible to spontaneous gliomas. Lipids 43(10): 951-959.
Mukherjee, P., Mulrooney, T.J., Marsh, J., Blair, D., Chiles, T.C., Seyfried, T.N. 2008. Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain. Molecular Cancer 7: 37.
Huysentruyt, L.C., Mukherjee, P., Banerjee, D., Shelton, L.M., Seyfried, T.N. 2008. Metastatic cancer cells with macrophage properties: evidence from a new murine tumor model. International Journal of Cancer 123(1): 73–84.
Kiebish, M.A., Han, X., Cheng, H., Lunceford, A., Clarke, C.F., Moon, H., Chuang, J.H., Seyfried, T.N. 2008. Lipidomic analysis and electron transport chain activities in C57BL/6J mouse brain mitochondria. Journal of Neurochemistry 106(1): 299–312.
Mukherjee, P., Faber, A.C., Shelton, L.M., Baek, R.C., Chiles, T.C., Seyfried, T.N. 2008. Ganglioside GM3 suppresses the pro-angiogenic effects of vascular endothelial growth factor and ganglioside GD1A. Journal of Lipid Research. 2008 Feb. 20 [Epub ahead of print].
Mukherjee, P., Faber, A.C., Shelton, L.M., Baek, R.C., Chiles, T.C., Seyfried, T.N. 2008. Thematic review series: sphingolipids. Ganglioside GM3 suppresses the proangiogenic effects of vascular endothelial growth factor and ganglioside GD1a. Journal of Lipid Research 49(5): 929–938.
Seyfried, N.T., Huysentruyt, L.C., Atwood, J.A. 3rd, Xia, Q., Seyfried, T.N., and Orlando, R. 2008. Up-regulation of NG2 proteoglycan and interferon-induced transmembrane proteins 1 and 3 in mouse astrocytoma: a membrane proteomics approach. Cancer Letters 263(2): 243–252.
Prien, J.M., Huysentruyt, L.C., Ashline, D.J., Lapadula, A.J., Seyfried, T.N., Reinhold, V.N. 2008. Differentiating N-linked glycan structural isomers in metastatic and nonmetastatic tumor cells using sequential mass spectrometry. Glycobiology 18(5): 353–366. Epub 2008 Feb 6.
Baek, R.C., Kasperzyk, J.L., Platt, F.M., Seyfried, T.N. 2008. N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice. Neurochemistry International 52(6): 1125–1133.
Todorova, M.T., Mantis, J.G., Le, M., Kim, C.Y., and Seyfried, T.N. 2006. Genetic and environmental interactions determine seizure susceptibility in epileptic EL mice. Genes, Brain, and Behavior 5(7): 518–27.
Abate, L.E., Mukherjee, P., and Seyfried, T.N. 2006. Gene-linked shift in ganglioside distribution influences growth and vascularity in a mouse astrocytoma. Journal of Neurochemistry 98(6): 1973–84.
Kasperzyk, J.L., d'Azzo A., Platt, F.M., Alroy, J., and Seyfried, T.N. 2005. Substrate reduction reduces gangliosides in postnatal cerebrum-brainstem and cerebellum in GM1 gangliosidosis mice. Journal of Lipid Research 46: 744–751.
Hauser, E.C., Kasperzyk, J.L., d'Azzo, A., and Seyfried, T.N. 2004. Inheritance of lysosomal acid beta-galactosidase activity and gangliosides in crosses of DBA/2J and knockout mice. Biochemical Genetics 42: 241–57.
Mukherjee, P., Abate, L.E., and Seyfried, T.N. 2004. Antiangiogenic and proapoptotic effects of dietary restriction on experimental mouse and human brain tumors. Clinical Cancer Research 10: 5622–5629.
Kasperzyk, J.L, El-Abbadi, M., Hauser, E.C., d'Azzo, A., Platt, F.M., and Seyfried, T.N. 2004. N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis. Journal of Neurochemistry 89: 645–53.
Venit, E.L., Shepard, B., and Seyfried, T.N. 2004. Oxygenation prevents sudden death in seizure-prone mice. Epilepsia 45: 993–996.
Mantis, J.G., Centeno, N.A., Todorova, M. T., McGowan, R, and Seyfried, T.N. 2004. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies. Nutrition & Metabolism 1: 11.
Seyfried, T.N, Sanderson, T.M, El-Abbadi, M.M, McGowan, R, Mukherjee, P. 2003. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. British Journal of Cancer 89: 1375–82.
Todorova, M. T., Dangler, C. A., Drage, M. G., Sheppard, B. J., Fox, J.G., and Seyfried, T. N. 2003. Sexual dysfunction and sudden death in epileptic male EL mice: inheritance and prevention with the ketogenic diet. Epilepsia 44: 25–31.
Mukherjee, P., El-Abbadi, M., Kasperzyk, J., and Seyfried, T. N. 2002. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. British Journal of Cancer 86: 1615–1621.
El-Abbadi, M., Seyfried, T. N., Yates, A. J., Orosz, C., and Lee, M. C. 2001. Ganglioside composition and histology of a spontaneous metastatic brain tumour in the VM mouse. British Journal of Cancer 85: 285–292.
Greene, A., Todorova, M. T., McGowan, R., and Seyfried, T. N. 2001. Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose levels. Epilepsia 42: 1371–1378.
Ranes, M.K., El-Abbadi, M., Manfredi, M.G., Mukherjee, P., Platt, F.M., Seyfried, T.N. 2001. N-butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours. British Journal of Cancer 84: 1107–1114.
Liang, D., and Seyfried, T. N. 2001. Genes differentially expressed in the kindled mouse brain. Molecular Brain Research 96: 94–102.
Seyfried, T. N. 2001. Perspectives on brain tumor formation involving macrophages, glia, and neural stem cells. Perspectives in Biology and Medicine 44: 263–282.
Todorova, M. T., Tandon, P., Madore, R. A., Stafstrom, C. E., and Seyfried, T. N. 2000. The ketogenic diet inhibits epileptogenesis in EL mice: a genetic model for idiopathic epilepsy. Epilepsia 41: 933–940.
Manfredi, M., Lim, G. S., Claffey, K. P., and Seyfried, T. N. 1999. Gangliosides influence angiogenesis in an experimental mouse brain tumor. Cancer Research 59: 5392–5397.
Todorova, M. T., Burwell, T. J., Seyfried, T. N. 1999. Environmental risk factors for multifactorial epilepsy in EL mice. Epilepsia 40: 1697–1707.
Poderycki, M. J., Simoes, J. M., Todorova, M. T., and Seyfried, T. N. 1998. Environmental influences on epilepsy gene mapping in EL mice. Journal of Neurogenetics 12: 67–86.
Brigande, J. V., Platt, F. M., and Seyfried, T. N. 1998. Inhibition of glycosphingolipid biosynthesis does not impair growth or morphogenesis of the postimplantation mouse embryo. Journal of Neurochemistry 70: 871–882.
Ecsedy, J. A., Yohe, H. C., Bergeron, A. J., and Seyfried, T. N. 1998. Tumor infiltrating macrophages influence the glycosphingolipid composition of mouse brain tumors. Journal of Lipid Research 39: 2218–2227.
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