Author
Maciek R. Antoniewicz
Other affiliations: Massachusetts Institute of Technology, University of Michigan, Delft University of Technology ...read more
Bio: Maciek R. Antoniewicz is an academic researcher from University of Delaware. The author has contributed to research in topics: Metabolic flux analysis & Pentose phosphate pathway. The author has an hindex of 47, co-authored 89 publications receiving 6638 citations. Previous affiliations of Maciek R. Antoniewicz include Massachusetts Institute of Technology & University of Michigan.
Papers published on a yearly basis
Papers
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TL;DR: This work presents a novel framework for the modeling of isotopic labeling systems that significantly reduces the number of system variables without any loss of information and is most efficient for the analysis of labeling by multiple isotopic tracers.
522 citations
Katholieke Universiteit Leuven1, University of Delaware2, University of California, Los Angeles3, University of Texas Southwestern Medical Center4, Case Western Reserve University5, Broad Institute6, Université catholique de Louvain7, University of Cambridge8, Cancer Research UK9, University of Luxembourg10, McGill University11, University of Glasgow12, Yale University13, Harvard University14, Cornell University15, Michigan State University16, University of California, San Diego17, University of Arizona18, University of Rochester19, Princeton University20, Medical Research Council21, ETH Zurich22, Massachusetts Institute of Technology23, University of Birmingham24, Saarland University25, Vanderbilt University26
TL;DR: Key issues in interpreting (13)C metabolite labeling patterns are reviewed, with the goal of drawing accurate conclusions from steady state and dynamic stable isotopic tracer experiments.
471 citations
TL;DR: An efficient algorithm is developed to determine accurate flux confidence intervals and it is demonstrated that confidence intervals obtained with this method closely approximate true flux uncertainty.
424 citations
TL;DR: It is shown that HK2 ablation decreases glycolysis and triggers oxidative phosphorylation (OXPHO) rendering HCC more susceptible to the OXPHO inhibitor metformin and to the FDA-approved drug sorafenib.
Abstract: Hepatocellular carcinoma (HCC) cells are metabolically distinct from normal hepatocytes by expressing the high-affinity hexokinase (HK2) and suppressing glucokinase (GCK). This is exploited to selectively target HCC. Hepatic HK2 deletion inhibits tumor incidence in a mouse model of hepatocarcinogenesis. Silencing HK2 in human HCC cells inhibits tumorigenesis and increases cell death, which cannot be restored by GCK or mitochondrial binding deficient HK2. Upon HK2 silencing, glucose flux to pyruvate and lactate is inhibited, but TCA fluxes are maintained. Serine uptake and glycine secretion are elevated suggesting increased requirement for one-carbon contribution. Consistently, vulnerability to serine depletion increases. The decrease in glycolysis is coupled to elevated oxidative phosphorylation, which is diminished by metformin, further increasing cell death and inhibiting tumor growth. Neither HK2 silencing nor metformin alone inhibits mTORC1, but their combination inhibits mTORC1 in an AMPK-independent and REDD1-dependent mechanism. Finally, HK2 silencing synergizes with sorafenib to inhibit tumor growth.
294 citations
TL;DR: A new role for glutamine as a lipogenic precursor is demonstrated and an alternative to the glutaminolysis pathway where flux of glutamine to lipogenic acetyl-CoA occurs via reductive carboxylation is proposed.
293 citations
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TL;DR: This book by a teacher of statistics (as well as a consultant for "experimenters") is a comprehensive study of the philosophical background for the statistical design of experiment.
Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON
13,333 citations
01 Jan 2000
3,536 citations
TL;DR: It is argued that altered metabolism has attained the status of a core hallmark of cancer.
2,623 citations
TL;DR: In this paper, the authors provide a detailed accounting of the biosynthetic requirements to construct a new cell and illustrate the importance of glycolysis in providing carbons to generate biomass.
Abstract: Warburg's observation that cancer cells exhibit a high rate of glycolysis even in the presence of oxygen (aerobic glycolysis) sparked debate over the role of glycolysis in normal and cancer cells. Although it has been established that defects in mitochondrial respiration are not the cause of cancer or aerobic glycolysis, the advantages of enhanced glycolysis in cancer remain controversial. Many cells ranging from microbes to lymphocytes use aerobic glycolysis during rapid proliferation, which suggests it may play a fundamental role in supporting cell growth. Here, we review how glycolysis contributes to the metabolic processes of dividing cells. We provide a detailed accounting of the biosynthetic requirements to construct a new cell and illustrate the importance of glycolysis in providing carbons to generate biomass. We argue that the major function of aerobic glycolysis is to maintain high levels of glycolytic intermediates to support anabolic reactions in cells, thus providing an explanation for why in...
2,251 citations
TL;DR: A conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis will progressively support the development of new strategies to treat human cancer.
Abstract: Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer.
1,850 citations