Dr Alexei Vazquez - Mathematical Models of Metabolism

Introduction

vazquez

Metabolism is essential for life and its alteration is implicated in multiple human diseases. The transformation from a normal cell to a cancerous one requires metabolic changes to fuel the high metabolic demands of cancer cells, including but not limited to cell proliferation and cell migration. In recent years there have been a number of new discoveries connecting known aberrations in oncogenic and tumour suppressor pathways with metabolic alterations required to sustain cell proliferation and migration. However, an understanding of the selective advantage of these metabolic alterations is still lacking.

Our group investigates cancer metabolism from an evolutionary viewpoint. We hypothesise that, given specific microenvironmental conditions and metabolic constraints, there is an optimal mode of cell metabolism required to achieve a particular metabolic objective (e.g. energy production, cell proliferation). This metabolic mode will offer an evolutionary advantage and therefore will be selected for during the time course of cancer development. First, we aim to uncover the metabolic objectives and metabolic constraints upon which natural selection is acting. Second, we aim to determine which known (and yet to be discovered) molecular alterations are driving the deterministic or stochastic occurrence of the optimal metabolic modes.

Specific projects:

  • Molecular crowding is a major constraint acting on cell metabolism: The Warburg effect is the optimal mode of energy metabolism under nutrient abundance and molecular crowding [1,3]
  • Proliferation and tissue remodelling are two main metabolic objectives of cancer: Proliferation and tissue remodelling are major drivers of the gene expression patterns of cancer tissues and they determine cancer subtypes with significant survival differences [2]
  • Metabolic response to drugs targeting cancer metabolism: the response or resistance to a drug targeting cancer metabolism is determined by the current metabolic state [4,5]

 Other funding:
            H2020 logo      

Lab Report

icon Vazquez Lab Report

Key Publications

Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, Burgos-Barragan G, Wit N, Dhayade S, Morton JP, Dornier E, Sumpton D, Mackay GM, Blyth K, Patel KJ, Niclou SP, Vazquez A. Increased formate overflow is a hallmark of oxidative cancer. Nat Commun. 2018; 9: 1368

Burgos-Barragan G, Wit N, Meiser J, Dingler FA, Pietzke M, Mulderrig L, Pontel LB, Rosado IV, Brewer TF, Cordell RL, Monks PS, Chang CJ, Vazquez A, Patel KJ. Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature. 2017; 548: 549-54

Meiser J, Tumanov S, Maddocks O, Labuschagne CF, Athineos D, Van Den Broek N, Mackay GM, Gottlieb E, Blyth K, Vousden K, Kamphorst JJ, Vazquez A. Serine one-carbon catabolism with formate overflow. Science Advances. 2016; 2: e1601273

Markert EK, Levine AJ, Vazquez A. Proliferation and tissue remodeling in cancer: the hallmarks revisited. Cell Death and Disease. 2012; 3: e397

Vazquez A, Markert EK, Oltvai ZN. Serine biosynthesis with one carbon catabolism and the glycine cleavage system represents a novel pathway for ATP generation. PLoS One. 2011; 6: e19538

Vazquez A, Liu J, Zhou Y, Oltvai ZN. Catabolic efficiency of aerobic glycolysis: The Warburg effect revisited. BMC Syst Biol. 2010; 4: 58

Biography

Education and qualifications

2002: PhD, Statistical and Biological Physics, International School of Advanced Studies, Italy
1997: MSc, Physics, University of Havana, Cuba
1995: BSc, Physics, University of Havana, Cuba

Appointments

2014-present: Junior Group Leader, CRUK Beatson Institute, Glasgow
2009-2014: Assistant Professor, Rutgers Cancer Institute of New Jersey, USA
2006-2009: Member, Institute for Advanced Study, Princeton, USA
2002-2006: Postdoctoral Fellow with Albert-Laszlo Barabasi, University of Notre Dame, USA

Honours and awards

Rutgers Cancer Institute of New Jersey Award in Breast Cancer Research, 2014
Cuban Physical Society Prize to Young Physicists, 1996

Recent Publications

2020

Dhayade S, Pietzke M, Wiesheu R, Tait-Mulder J, Athineos D, Sumpton D, Coffelt S, Blyth K, Vazquez A. Impact of Formate Supplementation on Body Weight and Plasma Amino Acids. Nutrients. 2020; 12(8):2181.

McGregor GH, Campbell AD, Fey SK, Tumanov S, Sumpton D, Blanco GR, Mackay G, Nixon C, Vazquez A, Sansom OJ, Kamphorst JJ. Targeting the Metabolic Response to Statin-Mediated Oxidative Stress Produces a Synergistic Antitumor Response. Cancer research. 2020;80(2):175-188.

Oizel K, Tait-Mulder J, Fernandez-de-Cossio-Diaz J, Pietzke M, Brunton H, Lilla S, Dhayade S, Athineos D, Blanco GR, Sumpton D, Mackay GM, Blyth K, Zanivan SR, Meiser J, Vazquez A. Formate induces a metabolic switch in nucleotide and energy metabolism. Cell death & disease. 2020;11:310.

Pietzke M, Burgos-Barragan G, Wit N, Tait-Mulder J, Sumpton D, Mackay GM, Patel KJ, Vazquez A. Amino acid dependent formaldehyde metabolism in mammals. Communications Chemistry. 2020;3(1):78.

Pietzke M, Meiser J, Vazquez A. Formate metabolism in health and disease. Molecular metabolism. 2020; 33: 23-37

Pietzke M, Vazquez A. Metabolite AutoPlotter - an application to process and visualise metabolite data in the web browser. Cancer Metab. 2020;8:15.

Vazquez A. Identification of putative calorie restriction mimetics using mammalian gene expression profiles. Open Biology. 2020;10(9):200158.

2019

Fernandez-de-Cossio-Diaz J, Mulet R, Vazquez A. Cell population heterogeneity driven by stochastic partition and growth optimality. Scientific reports. 2019; 9: 9406.

Pietzke M, Arroyo SF, Sumpton D, Mackay GM, Martin-Castillo B, Camps J, Joven J, Menendez JA, Vazquez A. Stratification of cancer and diabetes based on circulating levels of formate and glucose. Cancer & metabolism. 2019; 7: 3.

2018

Fernandez-de-Cossio-Diaz J, Vazquez A. A physical model of cell metabolism. Sci Rep. 2018; 8: 8349.

Halim S, Markert EK, Vazquez A. Analysis of cell proliferation and tissue remodelling uncovers a KLF4 activity score associated with poor prognosis in colorectal cancer. British journal of cancer. 2018; 119: 855-863.

Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, Burgos-Barragan G, Wit N, Dhayade S, Morton JP, Dornier E, Sumpton D, Mackay GM, Blyth K, Patel KJ, Niclou SP, Vazquez A. Increased formate overflow is a hallmark of oxidative cancer. Nat Commun. 2018; 9: 1368.

2017

Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, Vande Voorde J, Blyth K, Gottlieb E, Vazquez A, Kamphorst JJ. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation. Cell Rep 2017; 18: 647-58

Burgos-Barragan G, Wit N, Meiser J, Dingler FA, Pietzke M, Mulderrig L, Pontel LB, Rosado IV, Brewer TF, Cordell RL, Monks PS, Chang CJ, Vazquez A, Patel KJ. Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature 2017; 548: 549-54

Dolfi SC, Medina DJ, Kareddula A, Paratala B, Rose A, Dhami J, Chen S, Ganesan S, Mackay G, Vazquez A, Hirshfield KM. Riluzole exerts distinct antitumor effects from a metabotropic glutamate receptor 1-specific inhibitor on breast cancer cells. Oncotarget 2017; 8: 44639-53

Fernandez-de-Cossio-Diaz J, Vazquez A. Limits of aerobic metabolism in cancer cells. Sci Rep 2017; 7: 13488

Meiser J, Vazquez A, Hiller K. DJ1 at the interface between neuro-degeneration and cancer. Oncotarget 2017; 8: 9015-6

Vazquez A (2017) Overflow Metabolism: From Yeast to Marathon Runners. 1st Edition. Academic Press

2016

Meiser J, Tumanov S, Maddocks O, Labuschagne CF, Athineos D, Van Den Broek N, Mackay GM, Gottlieb E, Blyth K, Vousden K, Kamphorst JJ, Vazquez A. Serine one-carbon catabolism with formate overflow. Science Advances. 2016; 2: e1601273

Vazquez A, Oltvai ZN. Macromolecular crowding explains overflow metabolism in cells. Sci Rep. 2016; 6: 31007

Hirshfield KM, Tolkunov D, Zhong H, Ali SM, Stein MN, Murphy S, Vig H, Vazquez A, Glod J, Moss RA, Belyi V, Chan CS, Chen S, Goodell L, Foran D, Yelensky R, Palma NA, Sun JX, Miller VA, Stephens PJ, Ross JS, Kaufman H, Poplin E, Mehnert J, Tan AR, Bertino JR, Aisner J, DiPaola RS, Rodriguez-Rodriguez L, Ganesan S. Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers. Oncologist 2016; 21: 1315-1325

Meiser J, Vazquez A. Give it or take it: The flux of one-carbon in cancer cells. FEBS J. 2016; 283: 3695-704

Vazquez A, Kamphorst JJ, Markert EK, Schug ZT, Tardito S, Gottlieb E. Cancer metabolism at a glance. J Cell Sci. 2016; 129: 3367-73
 

Lab Members

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Postdoctoral Scientists

Zuzana Brabcova (collaboration with Gudmundur Helgason)
Holly Brunton

PhD Student

Martha-Maria Zarou (collaboration with Gudmundur Helgason)

Past member

Silvia Halim (Postdocotral Researcher, University of Oxford)
Johannes Meiser (FNR ATTRACT fellow, Luxembourg Institute for Health)
Kristel Oizel
Matthias Pietzke (Research Associate, Max Delbrück Centre for Molecular Medicine)

 

Research

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Read more about the Research Groups working at the Beatson Institute.

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Seminars

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Find out more about our seminars including our Distinguished Seminar Programme.

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