Dr Daniel A. Tennant

Institute of Metabolism and Systems Research
Senior Lecturer in Metabolic Biochemistry

Contact details

Address
Hypoxia and Metabolism Group
Institute of Metabolism and Systems Research
University of Birmingham
Birmingham
B15 2TT
UK


Dr. Daniel Tennant is a Senior Lecturer in Metabolic Biochemistry in the Institute of Metabolism and Systems Research (IMSR), situated on the second floor of the Institute of Biomedical Research. He uses stable isotope tracers to investigate changes in the use of nutrients in conditions where oxygen is limiting (hypoxia), or in the presence of genetic mutations that induce a hypoxia-like response. Dan applies the fundamental knowledge gained from these research projects to understand the pathogenesis of diseases where changes in oxygenation play a role; in particular, cancer.

 Dan has recently set up the Metabolic Tracer Analysis Core (MTAC) within the IMSR in order to develop novel means to analyse cellular and tissue metabolism using stable isotope tracer molecules, and collaborates with groups worldwide who are interested in using these techniques to study the metabolism of their system, or the metabolism of labelled product.

 Dr. Tennant publishes both primary research and reviews in high impact journals, including Nature Communications, Cell Metabolism, Nature Reviews Cancer and Cell, and is regularly asked to speak at international conferences.

Qualifications

 

  • Ph.D. (2005), Manchester University
  • MSci (2002) in Biochemistry, Cambridge University
  • BA (2001) in Natural Sciences, Cambridge University

Biography

Dan Tennant graduated with a BA (Hons) and MSci from the University of Cambridge in 2002. He went on to Manchester University to study for his PhD with Professors Caroline Dive and David Tomlinson. During this time, he developed a strong interest in low oxygen (hypoxia) and the means by which cells survive these conditions.

He then undertook a post-doctoral research post in the laboratory of Professor Eyal Gottlieb, studying tumour hypoxia and metabolism, and in particular a family of enzymes that sense cellular oxygen levels, known as Prolyl Hydroxylases (PHDs).

After just over five years, Dan started his own group at the University of Birmingham to investigate the ways in which cells alter their metabolism in order to survive hostile environments.

Teaching

 

  • BMedSc
  • MBChB
  • MRes Cancer Sciences

Postgraduate supervision

Dan Tennant is currently supervising doctoral students in projects investigating:

  • How cells modulate their metabolism in response to hypoxia
  • How tumour-associated genetic perturbations induce metabolic transformation

For any doctoral research enquiries, please see those associated with Dr. Tennant on findaphd.com or email: d.tennant@bham.ac.uk

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Current research in the Tennant laboratory concerns the means by which hypoxia leads to alterations in cellular metabolism, both via changes in the transcriptome and direct energetic and redox-based alterations. 

The research projects in the group are therefore aimed at addressing the following questions:

 

  1. How do changes in oxygen tension evoke alterations in cellular metabolism both directly and indirectly?
  2. In what way do changes in cellular metabolism during tumour growth lead to therapy resistance?
  3. Can we directly target metabolic transformation during tumour growth to evolve novel, more-specific anti-cancer therapies?

Research Groups and Centres

 MTAC – Metabolic Tracer Analysis Core

Publications


Hypoxia and metabolic adaptation of cancer cells. Eales KL, Hollinshead KE, Tennant DA. Oncogenesis. 2016 Jan 25;5:e190. doi: 10.1038/oncsis.2015.50

 Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism.Lussey-Lepoutre C, Hollinshead KE, Ludwig C, Menara M, Morin A, Castro-Vega LJ, Parker SJ, Janin M, Martinelli C, Ottolenghi C, Metallo C, Gimenez-Roqueplo AP, Favier J, Tennant DA. Nat Commun. 2015 Nov 2;6:8784. doi: 10.1038/ncomms9784.

Alterations in bone marrow metabolism are an early and consistent feature during the development of MGUS and multiple myeloma. Ludwig C, Williams DS, Bartlett DB, Essex SJ, McNee G, Allwood JW, Jewell E, Barkhuisen A, Parry H, Anandram S, Nicolson P, Gardener C, Seymour F, Basu S, Dunn WB, Moss PA, Pratt G, Tennant DA. Blood Cancer J. 2015 Oct 16;5:e359. doi: 10.1038/bcj.2015.85

A roadmap for interpreting (13)C metabolite labeling patterns from cells.  Buescher JM, Antoniewicz MR, Boros LG, Burgess SC, Brunengraber H, Clish CB, DeBerardinis RJ, Feron O, Frezza C, Ghesquiere B, Gottlieb E, Hiller K, Jones RG, Kamphorst JJ, Kibbey RG, Kimmelman AC, Locasale JW, Lunt SY, Maddocks OD, Malloy C, Metallo CM, Meuillet EJ, Munger J, Nöh K, Rabinowitz JD, Ralser M, Sauer U, Stephanopoulos G, St-Pierre J, Tennant DA, Wittmann C, Vander Heiden MG, Vazquez A, Vousden K, Young JD, Zamboni N, Fendt SM.  Curr Opin Biotechnol. 2015 Aug;34:189-201. doi: 10.1016/j.copbio.2015.02.003.

Metabolomic perfusate analysis during kidney machine perfusion: the pig provides an appropriate model for human studies. Nath J, Guy A, Smith TB, Cobbold M, Inston NG, Hodson J, Tennant DA, Ludwig C, Ready AR. PLoS One. 2014 Dec 12;9(12):e114818. doi: 10.1371/journal.pone.0114818.

Metabolomic analysis of perfusate during hypothermic machine perfusion of human cadaveric kidneys. Guy AJ, Nath J, Cobbold M, Ludwig C, Tennant DA, Inston NG, Ready AR.  Transplantation. 2015 Apr;99(4):754-9. doi: 10.1097/TP.0000000000000398.

Hypoxia inducible factors in liver disease and hepatocellular carcinoma: current understanding and future directions.  Wilson GK, Tennant DA, McKeating JA. J Hepatol. 2014 Dec;61(6):1397-406. doi: 10.1016/j.jhep.2014.08.025.

DiME: a scalable disease module identification algorithm with application to glioma progression. Liu Y, Tennant DA, Zhu Z, Heath JK, Yao X, He S. PLoS One. 2014 Feb 11;9(2):e86693. doi: 10.1371/journal.pone.0086693.

A role for cytosolic fumarate hydratase in urea cycle metabolism and renal neoplasia.  Adam J, Yang M, Bauerschmidt C, Kitagawa M, O'Flaherty L, Maheswaran P, Özkan G, Sahgal N, Baban D, Kato K, Saito K, Iino K, Igarashi K, Stratford M, Pugh C, Tennant DA, Ludwig C, Davies B, Ratcliffe PJ, El-Bahrawy M, Ashrafian H, Soga T, Pollard PJ. Cell Rep. 2013 May 30;3(5):1440-8. doi: 10.1016/j.celrep.2013.04.006.

Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells.  Favaro E, Bensaad K, Chong MG, Tennant DA, Ferguson DJ, Snell C, Steers G, Turley H, Li JL, Günther UL, Buffa FM, McIntyre A, Harris AL.  Cell Metab. 2012 Dec 5;16(6):751-64. doi: 10.1016/j.cmet.2012.10.017.

Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway.  Ashrafian H, Czibik G, Bellahcene M, Aksentijević D, Smith AC, Mitchell SJ, Dodd MS, Kirwan J, Byrne JJ, Ludwig C, Isackson H, Yavari A, Støttrup NB, Contractor H, Cahill TJ, Sahgal N, Ball DR, Birkler RI, Hargreaves I, Tennant DA, Land J, Lygate CA, Johannsen M, Kharbanda RK, Neubauer S, Redwood C, de Cabo R, Ahmet I, Talan M, Günther UL, Robinson AJ, Viant MR, Pollard PJ, Tyler DJ, Watkins H. Cell Metab. 2012 Mar 7;15(3):361-71. doi: 10.1016/j.cmet.2012.01.017.

From transcriptional profiling to tumor biology in pheochromocytoma and paraganglioma.  Cascón A, Tennant DA. Endocr Pathol. 2012 Mar;23(1):15-20. doi: 10.1007/s12022-012-9195-x

Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.  Frezza C, Zheng L, Tennant DA, Papkovsky DB, Hedley BA, Kalna G, Watson DG, Gottlieb E.  PLoS One. 2011;6(9):e24411. doi: 10.1371/journal.pone.0024411.

PK-M2 Makes Cells Sweeter on HIF1.  Tennant DA.  Cell. 2011 May 27;145(5):647-9. doi:0.1016/j.cell.2011.05.009.

HIF prolyl hydroxylase-3 mediates alpha-ketoglutarate-induced apoptosis and tumor suppression.  Tennant DA, Gottlieb E.  J Mol Med (Berl). 2010 Aug;88(8):839-49. doi: 10.1007/s00109-010-0627-0.

Targeting metabolic transformation for cancer therapy.  Tennant DA, Durán RV, Gottlieb E.  Nat Rev Cancer. 2010 Apr;10(4):267-77. doi: 10.1038/nrc2817.

IDH1 mutations in gliomas: when an enzyme loses its grip.  Frezza C, Tennant DA, Gottlieb E.  Cancer Cell. 2010 Jan 19;17(1):7-9. doi:10.1016/j.ccr.2009.12.031.

Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death.  Tennant DA, Frezza C, MacKenzie ED, Nguyen QD, Zheng L, Selak MA, Roberts DL, Dive C, Watson DG, Aboagye EO, Gottlieb E. Oncogene. 2009 Nov 12;28(45):4009-21. doi:10.1038/onc.2009.250

Metabolic transformation in cancer.  Tennant DA, Durán RV, Boulahbel H, Gottlieb E. Carcinogenesis. 2009 Aug;30(8):1269-80. doi: 10.1093/carcin/bgp070

Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells.  MacKenzie ED, Selak MA, Tennant DA, Payne LJ, Crosby S, Frederiksen CM, Watson DG, Gottlieb E. Mol Cell Biol. 2007 May;27(9):3282-9.