Thomas N. Seyfried

ORCID: 0000-0003-1491-3989
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About
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Research Areas
  • Cancer, Hypoxia, and Metabolism
  • Diet and metabolism studies
  • Mitochondrial Function and Pathology
  • Glycosylation and Glycoproteins Research
  • Neuroscience and Neuropharmacology Research
  • Lysosomal Storage Disorders Research
  • Metabolism and Genetic Disorders
  • Metabolism, Diabetes, and Cancer
  • ATP Synthase and ATPases Research
  • Glioma Diagnosis and Treatment
  • Metabolomics and Mass Spectrometry Studies
  • Adipose Tissue and Metabolism
  • Cellular transport and secretion
  • Cancer Research and Treatments
  • Caveolin-1 and cellular processes
  • Sphingolipid Metabolism and Signaling
  • Galectins and Cancer Biology
  • Cancer Cells and Metastasis
  • Cancer, Lipids, and Metabolism
  • Biochemical Analysis and Sensing Techniques
  • Epigenetics and DNA Methylation
  • Virus-based gene therapy research
  • RNA and protein synthesis mechanisms
  • Neuroblastoma Research and Treatments
  • Neurogenesis and neuroplasticity mechanisms

Boston College
2016-2025

Boston University
1994-2022

Kerman University of Medical Sciences
2020

Chestnut Hill College
2010-2015

Weatherford College
2015

Washington University in St. Louis
2007-2010

In-Q-Tel
2010

Dartmouth College
1999

Yale University
1979-1988

University of Illinois Urbana-Champaign
1976-1977

Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless or tissue origin. In contrast to normal cells, which derive most their usable from oxidative phosphorylation, cancer cells become heavily dependent on substrate level phosphorylation meet demands. Evidence reviewed supporting a general hypothesis genomic instability and essentially hallmarks cancer, including aerobic glycolysis (Warburg effect), can be linked...

10.1186/1743-7075-7-7 article EN cc-by Nutrition & Metabolism 2010-01-01

Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect diet, the frequency and circadian timing meals, potential benefits intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, abnormal from an evolutionary perspective. Emerging findings studies animal models human subjects suggest that restriction as...

10.1073/pnas.1413965111 article EN Proceedings of the National Academy of Sciences 2014-11-17

Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and 13C-labeling, we have detected ITA in both macrophage-like VM-M3 RAW 264.7 tumor cell lines well stimulated unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide IFN-γ markedly increased production secretion. Crude extracts synthesize via decarboxylation cis-aconitate, indicative novel cis-aconitic decarboxylase...

10.1021/ja2070889 article EN Journal of the American Chemical Society 2011-09-27

Management of glioblastoma multiforme (GBM) has been difficult using standard therapy (radiation with temozolomide chemotherapy). The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered restricted amounts, can also target energy metabolism brain tumors. We report the case a 65-year-old woman who presented progressive memory loss, chronic headaches, nausea, and right hemisphere multi-centric tumor seen magnetic resonance imaging (MRI). Following...

10.1186/1743-7075-7-33 article EN cc-by Nutrition & Metabolism 2010-01-01

Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer are unable effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation viability of cultured tumor cells. As Warburg effect is especially prominent in metastatic cells, we hypothesized dietary supplementation would progression vivo. Proliferation were...

10.1002/ijc.28809 article EN International Journal of Cancer 2014-02-26

Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults is the second leading cause death children. Many current therapies for malignant tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting health vitality normal cells. In contrast cells, which lack metabolic flexibility are largely dependent on glucose growth survival, can metabolize both ketone bodies energy. This study...

10.1186/1743-7075-4-5 article EN cc-by Nutrition & Metabolism 2007-02-21

Otto Warburg first proposed that cancer originated from irreversible injury to mitochondrial respiration, but the structural basis for this has remained elusive. Cardiolipin (CL) is a complex phospholipid found almost exclusively in inner membrane and intimately involved maintaining functionality integrity. Abnormalities CL can impair function bioenergetics. We used shotgun lipidomics analyze content composition highly purified brain mitochondria C57BL/6J (B6) VM/Dk (VM) inbred strains...

10.1194/jlr.m800319-jlr200 article EN cc-by Journal of Lipid Research 2008-08-14

Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both ketone bodies. We examined the first time potential efficacy of dietary therapies reduce plasma elevate bodies in CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), ketogenic (KD-UR), SD restricted to 40% (SD-R), or KD control (KD-R). Body weights, tumour glucose,...

10.1038/sj.bjc.6601269 article EN cc-by-nc-sa British Journal of Cancer 2003-09-30

Abstract Malignant brain tumors are a significant health problem in children and adults often unmanageable. As metabolic disorder involving the dysregulation of glycolysis respiration, malignant cancer is potentially manageable through changes environment. A radically different approach to management proposed that combines control analysis with evolutionarily conserved capacity normal cells survive extreme shifts physiological In contrast largely dependent on for energy, neurons glia readily...

10.1186/1743-7075-2-30 article EN cc-by Nutrition & Metabolism 2005-10-21

Caloric restriction (CR) involves underfeeding and has long been recognized as a dietary therapy that improves health increases longevity. In contrast to severe fasting or starvation, CR reduces total food intake without causing nutritional deficiencies. Although an effective antiseizure since the time of ancient Greeks, mechanism by which inhibits seizures remains obscure. The influence on seizure susceptibility was investigated at both juvenile (30 days) adult (70 ages in EL mouse, genetic...

10.1046/j.1528-1157.2001.17601.x article EN Epilepsia 2001-11-10

The neurological mutant mouse strain El is a model for complex partial seizures in humans. inheritance of epileptic with seven conventional chromosomal markers and over 60 endogenous proviral was studied by means backcrosses two seizure-resistant strains, DBA/2J ABP/LeJ. major gene responsible this phenotype ( El-1 ) localized to region distal respect the centromere on chromosome 9. At least one other gene, El-2 , linked 2, also influences seizure phenotype. In addition, potential modifier...

10.1126/science.1871601 article EN Science 1991-08-09

Introduction Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is low carbohydrate, high fat decreases blood and elevates ketones has been shown slow progression in animals humans. tumor vasculature hypoxic pockets promote further increase of cancers. Hyperbaric oxygen therapy (HBO2T) saturates tumors with oxygen, reversing promoting effects hypoxia. Since these non-toxic therapies exploit...

10.1371/journal.pone.0065522 article EN cc-by PLoS ONE 2013-06-05

Cancer is widely considered a genetic disease involving nuclear mutations in oncogenes and tumor suppressor genes. This view persists despite the numerous inconsistencies associated with somatic mutation theory. In contrast to theory, emerging evidence suggests that cancer mitochondrial metabolic disease, according original theory of Otto Warburg. The findings are reviewed from cytoplasm transfer experiments relate origin cancer. these difficult reconcile but consistent notion primarily disease.

10.3389/fcell.2015.00043 article EN cc-by Frontiers in Cell and Developmental Biology 2015-07-07

Bacterially derived lipopolysaccharide (LPS) stimulates naive B lymphocytes to differentiate into immunoglobulin (Ig)-secreting plasma cells. Differentiation of is characterized by a proliferative phase followed expansion the intracellular membrane secretory network support Ig production. A key question in lymphocyte biology how cells reprogram metabolism de novo lipogenesis necessary for proliferation and endomembrane response LPS. We report that extracellularly acquired glucose...

10.1074/jbc.m114.551051 article EN cc-by Journal of Biological Chemistry 2014-01-28

Abstract The objective of this study was to characterize the lipidome and electron transport chain activities in purified non‐synaptic (NS) synaptic (Syn) mitochondria from C57BL/6J mouse cerebral cortex. Contamination subcellular membranes, especially myelin, has hindered past attempts accurately lipid composition brain mitochondria. An improved Ficoll sucrose discontinuous gradient method employed that yielded highly enriched mitochondrial populations free myelin contamination. Complexes...

10.1111/j.1471-4159.2008.05383.x article EN Journal of Neurochemistry 2008-03-27
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