Editorial Boards

ASN NEURO, Senior Editor
Journal of Lipid Research
Neurochemical Research
Nutrition & Metabolism

Academic Profile

Our research program focuses on mechanisms by which metabolic therapy manages chronic diseases such as epilepsy, neurodegenerative lipid storage diseases, and cancer.  The metabolic therapies include caloric restriction, fasting, and ketogenic diets.  Our approach is based on the idea that compensatory metabolic pathways are capable of modifying the pathogenesis of complex diseases. Global shifts in metabolic environment can neutralize molecular pathology.  In the case of cancer, these therapies target and kill tumor cells while enhancing the physiological health of normal cells.  The neurochemical and genetic mechanisms of these phenomena are under investigation in novel animal models and include the processes of inflammation, cellular physiology, angiogenesis, and lipid biochemistry.

 

Representative Publications

Arthur JR, Lee JP, Snyder EY, Seyfried TN. Therapeutic effects of stem cells and substrate reduction in juvenile sandhoff mice.
Neurochem Res. 2012 Jun;37(6):1335-43. Epub 2012 Feb 25.

Urits I, Mukherjee P, Meidenbauer J, Seyfried TN. Dietary restriction promotes vessel maturation in a mouse astrocytoma.
J Oncol. 2012;2012:264039. Epub 2011 Dec 27.

Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P.
Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res. 2011 Aug 30.

Huysentruyt LC, Akgoc Z, Seyfried TN. Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme? ASN Neuro. 2011 Sep 22;3(4). pii: e00064. doi: 10.1042/AN20110011.

Arthur JR, Heinecke KA, Seyfried TN. Filipin recognizes both GM1 and cholesterol in GM1 gangliosidosis mouse brain. J Lipid Res. 2011 Jul;52(7):1345-51. Epub 2011 Apr 20.

Mulrooney TJ, Marsh J, Urits I, Seyfried TN, Mukherjee P. PLoS One. 2011 Mar 30;6(3):e18085.

Heinecke KA, Peacock BN, Blazar BR, Tolar J, Seyfried TN. Lipid composition of whole brain and cerebellum in Hurler syndrome (MPS IH) mice. Neurochem Res. 2011 Sep;36(9):1669-76. Epub 2011 Jan 21.

Meidenbauer JJ, Mantis JG, Seyfried TN. The EL mouse: a natural model of autism and epilepsy. Epilepsia. 2011 Feb;52(2):347-57. doi: 10.1111/j.1528-1167.2010.02898.x. Epub 2011 Jan 4.

Baek RC, Broekman ML, Leroy SG, Tierney LA, Sandberg MA, d'Azzo A, Seyfried TN, Sena-Esteves M. AAV-mediated gene delivery in adult GM1-gangliosidosis mice corrects lysosomal storage in CNS and improves survival. PLoS One. 2010 Oct 18;5(10):e13468.

Huysentruyt LC, Seyfried TN. Perspectives on the mesenchymal origin of metastatic cancer. Cancer Metastasis Rev. 2010 Dec;29(4):695-707. Review.

Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Metabolic management of brain cancer.
Biochim Biophys Acta. 2011 Jun;1807(6):577-94. Epub 2010 Sep 8. Review.

Denny CA, Desplats PA, Thomas EA, Seyfried TN. Cerebellar lipid differences between R6/1 transgenic mice and humans with Huntington's disease. J Neurochem. 2010 Nov;115(3):748-58.

Shelton LM, Huysentruyt LC, Mukherjee P, Seyfried TN.
Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.
ASN Neuro. 2010 Jul 23;2(3):e00038.

Seyfried TN, Mukherjee P.  Ganglioside GM3 Is Antiangiogenic in Malignant Brain Cancer. J Oncol. 2010;2010:961243. Epub 2010 Jun 20.

Seyfried TN, Shelton LM, Mukherjee P. Does the existing standard of care increase glioblastoma energy metabolism?
Lancet Oncol. 2010 Sep;11(9):811-3. Epub 2010 Jul 13.

Shelton LM, Huysentruyt LC, Seyfried TN. Glutamine targeting inhibits systemic metastasis in the VM-M3 murine tumor model.
Int J Cancer. 2010 Nov 15;127(10):2478-85.

Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report. Nutr Metab (Lond). 2010 Apr 22;7:33.

Seyfried, T.N., Shelton, L.M. 2010. Cancer as a metabolic disease. Nutrition & Metabolism 7:7.

Huysentruyt, L.C., Shelton, L.M., Seyfried, T.N. 2010. Influence of methotrexate and cisplatin on tumor progression and survival in the VM mouse model of systemic metastatic cancer. International Journal of Cancer 126(1): 65–72.

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.

Marsh, J., Mukherjee, P., Seyfried, T.N. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet. Nutrition & Metabolism 5: 33.

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 4(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. 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.