Professor Kevin Brindle

Kevin Brindle

University position

Professor

Professor Kevin Brindle is pleased to consider applications from prospective PhD students.

Departments

Department of Biochemistry

Institutes

Cancer Research UK, Cambridge Research Institute

Email

kmb@mole.bio.cam.ac.uk

Home page

http://www.bioc.cam.ac.uk/uto/bri... (personal home page)

Research Themes

Clinical and Veterinary Neuroscience

Cellular and Molecular Neuroscience

Interests

We have developed non-invasive magnetic resonance imaging (MRI) techniques that enable us to track labelled cells that have been implanted in the CNS. This work has been conducted in collaboration with Robin Franklin. In addition we are developing a gene reporter construct for MRI, that can be used in conjunction with our cell labelling techniques. Thus, following stem cell transplantation into the CNS, we should be able to tell not only where the cells are but also whether they have differentiated.

Magnetic resonance image of a rat brain 7 days after the implantation of labelled oligodendrocytes
Magnetic resonance image of a rat brain 7 days after the implantation of labelled oligodendrocytes
Click image to view full-size

Research Focus

Keywords

imaging

cells

MRI

Clinical conditions

Spinal cord injury

Equipment

Magnetic resonance imaging (MRI)

Collaborators

Cambridge

Robin Franklin

Associated News Items


Key publications

Hu D-E, Kettunen MI, Brindle KM (2005), “Monitoring T-lymphocyte trafficking in tumors undergoing immune rejection” Magn Reson Med 54:1473-1479 Details

Publications

2014

Dzien P, Kettunen MI, Marco-Rius I, Serrao EM, Rodrigues TB, Larkin TJ, Timm KN, Brindle KM (2014), “13 C magnetic resonance spectroscopic imaging of hyperpolarized [1-13 C, U-2 H5 ] ethanol oxidation can be used to assess aldehyde dehydrogenase activity in vivo.” Magn Reson Med Details

Larkin TJ, Canuto HC, Kettunen MI, Booth TC, Hu DE, Krishnan AS, Bohndiek SE, Neves AA, McLachlan C, Hobson MP, Brindle KM (2014), “Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment.” Magn Reson Med 71(1):402-10 Details

Lewis DY, Boren J, Shaw GL, Bielik R, Ramos-Montoya A, Larkin TJ, Martins CP, Neal DE, Soloviev D, Brindle KM (2014), “Late Imaging with [1-11C]Acetate Improves Detection of Tumor Fatty Acid Synthesis with PET.” J Nucl Med Details

Marco-Rius I, Bohndiek SE, Kettunen MI, Larkin TJ, Basharat M, Seeley C, Brindle KM (2014), “Quantitation of a spin polarization-induced nuclear Overhauser effect (SPINOE) between a hyperpolarized (13) C-labeled cell metabolite and water protons.” Contrast Media Mol Imaging 9(2):182-6 Details

Neves AA, Brindle KM (2014), “Imaging cell death.” J Nucl Med 55(1):1-4 Details

Ong CA, Shannon NB, Ross-Innes CS, O'Donovan M, Rueda OM, Hu DE, Kettunen MI, Walker CE, Noorani A, Hardwick RH, Caldas C, Brindle K, Fitzgerald RC (2014), “Amplification of TRIM44: Pairing a Prognostic Target With Potential Therapeutic Strategy.” J Natl Cancer Inst 106(5) Details

Patrick PS, Hammersley J, Loizou L, Kettunen MI, Rodrigues TB, Hu DE, Tee SS, Hesketh R, Lyons SK, Soloviev D, Lewis DY, Aime S, Fulton SM, Brindle KM (2014), “Dual-modality gene reporter for in vivo imaging.” Proc Natl Acad Sci U S A 111(1):415-20 Details

Patrick PS, Kettunen MI, Tee SS, Rodrigues TB, Serrao E, Timm KN, McGuire S, Brindle KM (2014), “Detection of transgene expression using hyperpolarized 13 C urea and diffusion-weighted magnetic resonance spectroscopy.” Magn Reson Med Details

Patrick PS, Lyons SK, Rodrigues TB, Brindle KM (2014), “Oatp1 Enhances Bioluminescence by Acting as a Plasma Membrane Transporter for D-luciferin.” Mol Imaging Biol Details

Rodrigues TB, Serrao EM, Kennedy BW, Hu DE, Kettunen MI, Brindle KM (2014), “Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose.” Nat Med 20(1):93-7 Details

Rodriguez E, Mannion L, D'Santos P, Griffiths M, Arends MJ, Brindle KM, Lyons SK (2014), “Versatile and enhanced tumour modelling in mice via somatic cell transduction.” J Pathol 232(4):449-57 Details

Schmidt R, Laustsen C, Dumez JN, Kettunen MI, Serrao EM, Marco-Rius I, Brindle KM, Ardenkjaer-Larsen JH, Frydman L (2014), “In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding.” J Magn Reson 240:8-15 Details

Zecchini V, Madhu B, Russell R, Pértega-Gomes N, Warren A, Gaude E, Borlido J, Stark R, Ireland-Zecchini H, Rao R, Scott H, Boren J, Massie C, Asim M, Brindle K, Griffiths J, Frezza C, Neal DE, Mills IG (2014), “Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer.” EMBO J Details

2013

Kettunen MI, Kennedy BW, Hu DE, Brindle KM (2013), “Spin echo measurements of the extravasation and tumor cell uptake of hyperpolarized [1-(13) C]lactate and [1-(13) C]pyruvate.” Magn Reson Med 70(5):1200-9 Details

Lyons SK, Patrick PS, Brindle KM (2013), “Imaging mouse cancer models in vivo using reporter transgenes.” Cold Spring Harb Protoc 2013(8):685-99 Details

Marco-Rius I, Tayler MC, Kettunen MI, Larkin TJ, Timm KN, Serrao EM, Rodrigues TB, Pileio G, Ardenkjaer-Larsen JH, Levitt MH, Brindle KM (2013), “Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse.” NMR Biomed 26(12):1696-704 Details

Neves AA, Stöckmann H, Wainman YA, Kuo JC, Fawcett S, Leeper FJ, Brindle KM (2013), “Imaging cell surface glycosylation in vivo using "double click" chemistry.” Bioconjug Chem 24(6):934-41 Details

Roberts EW, Deonarine A, Jones JO, Denton AE, Feig C, Lyons SK, Espeli M, Kraman M, McKenna B, Wells RJ, Zhao Q, Caballero OL, Larder R, Coll AP, O'Rahilly S, Brindle KM, Teichmann SA, Tuveson DA, Fearon DT (2013), “Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia.” J Exp Med 210(6):1137-51 Details

Stairs S, Neves AA, Stöckmann H, Wainman YA, Ireland-Zecchini H, Brindle KM, Leeper FJ (2013), “Metabolic glycan imaging by isonitrile-tetrazine click chemistry.” Chembiochem 14(9):1063-7 Details

Steuwe C, Patel II, Ul-Hasan M, Schreiner A, Boren J, Brindle KM, Reichelt S, Mahajan S (2013), “CARS based label-free assay for assessment of drugs by monitoring lipid droplets in tumour cells.” J Biophotonics Details

Wainman YA, Neves AA, Stairs S, Stöckmann H, Ireland-Zecchini H, Brindle KM, Leeper FJ (2013), “Dual-sugar imaging using isonitrile and azido-based click chemistries.” Org Biomol Chem 11(42):7297-300 Details

2012

Bird-Lieberman EL, Neves AA, Lao-Sirieix P, O'Donovan M, Novelli M, Lovat LB, Eng WS, Mahal LK, Brindle KM, Fitzgerald RC (2012), “Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett's esophagus.” Nat Med 18(2):315-21 Details

Bohndiek SE, Kettunen MI, Hu DE, Brindle KM (2012), “Hyperpolarized (13)C spectroscopy detects early changes in tumor vasculature and metabolism after VEGF neutralization.” Cancer Res 72(4):854-64 Details

Boren J, Brindle KM (2012), “Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation.” Cell Death Differ 19(9):1561-70 Details

Brindle K (2012), “Watching tumours gasp and die with MRI: the promise of hyperpolarised 13C MR spectroscopic imaging.” Br J Radiol 85(1014):697-708 Details

Clatworthy MR, Kettunen MI, Hu DE, Mathews RJ, Witney TH, Kennedy BW, Bohndiek SE, Gallagher FA, Jarvis LB, Smith KG, Brindle KM (2012), “Magnetic resonance imaging with hyperpolarized [1,4-(13)C2]fumarate allows detection of early renal acute tubular necrosis.” Proc Natl Acad Sci U S A 109(33):13374-9 Details

Kennedy BW, Kettunen MI, Hu DE, Brindle KM (2012), “Probing lactate dehydrogenase activity in tumors by measuring hydrogen/deuterium exchange in hyperpolarized l-[1-(13)C,U-(2)H]lactate.” J Am Chem Soc 134(10):4969-77 Details

2011

Bohndiek SE, Kettunen MI, Hu DE, Kennedy BW, Boren J, Gallagher FA, Brindle KM (2011), “Hyperpolarized [1-13C]-ascorbic and dehydroascorbic acid: vitamin C as a probe for imaging redox status in vivo.” J Am Chem Soc 133(30):11795-801 Details

Brindle KM, Bohndiek SE, Gallagher FA, Kettunen MI (2011), “Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy.” Magn Reson Med 66(2):505-19 Details

Crossan GP, van der Weyden L, Rosado IV, Langevin F, Gaillard PH, McIntyre RE, Sanger Mouse Genetics Project, Gallagher F, Kettunen MI, Lewis DY, Brindle K, Arends MJ, Adams DJ, Patel KJ (2011), “Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia.” Nat Genet 43(2):147-52 Details

Gallagher FA, Bohndiek SE, Kettunen MI, Lewis DY, Soloviev D, Brindle KM (2011), “Hyperpolarized 13C MRI and PET: in vivo tumor biochemistry.” J Nucl Med 52(9):1333-6 Details

Gallagher FA, Kettunen MI, Brindle KM (2011), “Imaging pH with hyperpolarized 13C.” NMR Biomed 24(8):1006-15 Details

Gallagher FA, Kettunen MI, Day SE, Hu DE, Karlsson M, Gisselsson A, Lerche MH, Brindle KM (2011), “Detection of tumor glutamate metabolism in vivo using (13)C magnetic resonance spectroscopy and hyperpolarized [1-(13)C]glutamate.” Magn Reson Med 66(1):18-23 Details

Massie CE, Lynch A, Ramos-Montoya A, Boren J, Stark R, Fazli L, Warren A, Scott H, Madhu B, Sharma N, Bon H, Zecchini V, Smith DM, Denicola GM, Mathews N, Osborne M, Hadfield J, Macarthur S, Adryan B, Lyons SK, Brindle KM, Griffiths J, Gleave ME, Rennie PS, Neal DE, Mills IG (2011), “The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis.” EMBO J 30(13):2719-33 Details

Neves AA, Stöckmann H, Harmston RR, Pryor HJ, Alam IS, Ireland-Zecchini H, Lewis DY, Lyons SK, Leeper FJ, Brindle KM (2011), “Imaging sialylated tumor cell glycans in vivo.” FASEB J 25(8):2528-37 Details

Sleigh A, Raymond-Barker P, Thackray K, Porter D, Hatunic M, Vottero A, Burren C, Mitchell C, McIntyre M, Brage S, Carpenter TA, Murgatroyd PR, Brindle KM, Kemp GJ, O'Rahilly S, Semple RK, Savage DB (2011), “Mitochondrial dysfunction in patients with primary congenital insulin resistance.” J Clin Invest 121(6):2457-61 Details

Stöckmann H, Neves AA, Day HA, Stairs S, Brindle KM, Leeper FJ (2011), “(E,E)-1,5-Cyclooctadiene: a small and fast click-chemistry multitalent.” Chem Commun (Camb) 47(25):7203-5 Details

Stöckmann H, Neves AA, Stairs S, Brindle KM, Leeper FJ (2011), “Exploring isonitrile-based click chemistry for ligation with biomolecules.” Org Biomol Chem 9(21):7303-5 Details

Stöckmann H, Neves AA, Stairs S, Ireland-Zecchini H, Brindle KM, Leeper FJ (2011), “Development and evaluation of new cyclooctynes for cell surface glycan imaging in cancer cells.” Chem Sci 2(5):932-936 Details

Witney TH, Kettunen MI, Brindle KM (2011), “Kinetic modeling of hyperpolarized 13C label exchange between pyruvate and lactate in tumor cells.” J Biol Chem 286(28):24572-80 Details

2010

Alam IS, Neves AA, Witney TH, Boren J, Brindle KM (2010), “Comparison of the C2A domain of synaptotagmin-I and annexin-V as probes for detecting cell death.” Bioconjug Chem 21(5):884-91 Details

Bohndiek SE, Brindle KM (2010), “Imaging and 'omic' methods for the molecular diagnosis of cancer.” Expert Rev Mol Diagn 10(4):417-34 Details

Bohndiek SE, Kettunen MI, Hu DE, Witney TH, Kennedy BW, Gallagher FA, Brindle KM (2010), “Detection of tumor response to a vascular disrupting agent by hyperpolarized 13C magnetic resonance spectroscopy.” Mol Cancer Ther 9(12):3278-88 Details

Kettunen MI, Hu DE, Witney TH, McLaughlin R, Gallagher FA, Bohndiek SE, Day SE, Brindle KM (2010), “Magnetization transfer measurements of exchange between hyperpolarized [1-13C]pyruvate and [1-13C]lactate in a murine lymphoma.” Magn Reson Med 63(4):872-80 Details

Witney TH, Brindle KM (2010), “Imaging tumour cell metabolism using hyperpolarized 13C magnetic resonance spectroscopy.” Biochem Soc Trans 38(5):1220-4 Details

Witney TH, Kettunen MI, Hu DE, Gallagher FA, Bohndiek SE, Napolitano R, Brindle KM (2010), “Detecting treatment response in a model of human breast adenocarcinoma using hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate.” Br J Cancer 103(9):1400-6 Details

2009

Canuto HC, McLachlan C, Kettunen MI, Velic M, Krishnan AS, Neves AA, de Backer M, Hu DE, Hobson MP, Brindle KM (2009), “Characterization of image heterogeneity using 2D Minkowski functionals increases the sensitivity of detection of a targeted MRI contrast agent.” Magn Reson Med 61(5):1218-24 Details

Gallagher FA, Kettunen MI, Hu DE, Jensen PR, Zandt RI, Karlsson M, Gisselsson A, Nelson SK, Witney TH, Bohndiek SE, Hansson G, Peitersen T, Lerche MH, Brindle KM (2009), “Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors.” Proc Natl Acad Sci U S A 106(47):19801-6 Details

Witney TH, Kettunen MI, Day SE, Hu DE, Neves AA, Gallagher FA, Fulton SM, Brindle KM (2009), “A comparison between radiolabeled fluorodeoxyglucose uptake and hyperpolarized (13)C-labeled pyruvate utilization as methods for detecting tumor response to treatment.” Neoplasia 11(6):574-82, 1 p following 582 Details

2008

Brindle K (2008), “New approaches for imaging tumour responses to treatment.” Nat Rev Cancer 8(2):94-107 Details

Gallagher FA, Kettunen MI, Day SE, Hu DE, Ardenkjaer-Larsen JH, Zandt Ri, Jensen PR, Karlsson M, Golman K, Lerche MH, Brindle KM (2008), “Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate.” Nature 453(7197):940-3 Details

Gallagher FA, Kettunen MI, Day SE, Lerche M, Brindle KM (2008), “13C MR spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C-labeled glutamine.” Magn Reson Med 60(2):253-7 Details

Krishnan AS, Neves AA, de Backer MM, Hu DE, Davletov B, Kettunen MI, Brindle KM (2008), “Detection of cell death in tumors by using MR imaging and a gadolinium-based targeted contrast agent.” Radiology 246(3):854-62 Details

2007

Browne RA, Brindle KM (2007), “H NMR-based metabolite profiling as a potential selection tool for breeding passive resistance against Fusarium head blight (FHB) in wheat.” Mol Plant Pathol 8(4):401-10 Details

Bundy JG, Papp B, Harmston R, Browne RA, Clayson EM, Burton N, Reece RJ, Oliver SG, Brindle KM (2007), “Evaluation of predicted network modules in yeast metabolism using NMR-based metabolite profiling.” Genome Res 17(4):510-9 Details

Day SE, Kettunen MI, Gallagher FA, Hu DE, Lerche M, Wolber J, Golman K, Ardenkjaer-Larsen JH, Brindle KM (2007), “Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy.” Nat Med 13(11):1382-7 Details

Neves AA, Krishnan AS, Kettunen MI, Hu DE, Backer MM, Davletov B, Brindle KM (2007), “A paramagnetic nanoprobe to detect tumor cell death using magnetic resonance imaging.” Nano Lett 7(5):1419-23 Details

2006

Bundy JG, Iyer NG, Gentile MS, Hu DE, Kettunen M, Maia AT, Thorne NP, Brenton JD, Caldas C, Brindle KM (2006), “Metabolic consequences of p300 gene deletion in human colon cancer cells.” Cancer Res 66(15):7606-14 Details

Dunning MD, Kettunen MI, Ffrench Constant C, Franklin RJ, Brindle KM (2006), “Magnetic resonance imaging of functional Schwann cell transplants labelled with magnetic microspheres.” Neuroimage 31(1):172-80 Details

Kirschenlohr HL, Griffin JL, Clarke SC, Rhydwen R, Grace AA, Schofield PM, Brindle KM, Metcalfe JC (2006), “Proton NMR analysis of plasma is a weak predictor of coronary artery disease.” Nat Med 12(6):705-10 Details

Neves AA, Brindle KM (2006), “Assessing responses to cancer therapy using molecular imaging.” Biochim Biophys Acta 1766(2):242-61 Details

Neves AA, Medcalf N, Smith M, Brindle KM (2006), “Evaluation of engineered meniscal cartilage constructs based on different scaffold geometries using magnetic resonance imaging and spectroscopy.” Tissue Eng 12(1):53-62 Details

2005

Bundy JG, Willey TL, Castell RS, Ellar DJ, Brindle KM (2005), “Discrimination of pathogenic clinical isolates and laboratory strains of Bacillus cereus by NMR-based metabolomic profiling.” FEMS Microbiol Lett 242(1):127-36 Details

Hu DE, Brindle KM (2005), “Immune cell-induced synthesis of NO and reactive oxygen species in lymphoma cells causes their death by apoptosis.” FEBS Lett 579(13):2833-41 Details

Neves AA, Medcalf N, Brindle KM (2005), “Influence of stirring-induced mixing on cell proliferation and extracellular matrix deposition in meniscal cartilage constructs based on polyethylene terephthalate scaffolds.” Biomaterials 26(23):4828-36 Details

Schmitz JE, Kettunen MI, Hu DE, Brindle KM (2005), “1H MRS-visible lipids accumulate during apoptosis of lymphoma cells in vitro and in vivo.” Magn Reson Med 54(1):43-50 Details

2004

Dunning MD, Lakatos A, Loizou L, Kettunen M, ffrench-Constant C, Brindle KM, Franklin RJ (2004), “Superparamagnetic iron oxide-labeled Schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS.” J Neurosci 24(44):9799-810 Details

Hu DE, Dyke SO, Moore AM, Thomsen LL, Brindle KM (2004), “Tumor cell-derived nitric oxide is involved in the immune-rejection of an immunogenic murine lymphoma.” Cancer Res 64(1):152-61 Details

Hu DE, Moore AM, Thomsen LL, Brindle KM (2004), “Uric acid promotes tumor immune rejection.” Cancer Res 64(15):5059-62 Details

Jung HI, Kettunen MI, Davletov B, Brindle KM (2004), “Detection of apoptosis using the C2A domain of synaptotagmin I.” Bioconjug Chem 15(5):983-7 Details

2003

Brindle KM (2003), “Molecular imaging using magnetic resonance: new tools for the development of tumour therapy.” Br J Radiol 76 Spec No 2:S111-7 Details

Hu DE, Beauregard DA, Bearchell MC, Thomsen LL, Brindle KM (2003), “Early detection of tumour immune-rejection using magnetic resonance imaging.” Br J Cancer 88(7):1135-42 Details

1999

Thelwall PE, Brindle KM (1999), “Analysis of CHO-K1 cell growth in a fixed bed bioreactor using magnetic resonance spectroscopy and imaging.” Cytotechnology 30(1-3):121-32 Details

1997

Williams SN, Callies RM, Brindle KM (1997), “Mapping of oxygen tension and cell distribution in a hollow-fiber bioreactor using magnetic resonance imaging.” Biotechnol Bioeng 56(1):56-61 Details