Molecular Medicine group

Contact


Dr Tanya Knowles 
+44 (0)20 7594 1936
t.knowles@imperial.ac.uk

Lead academic
Professor Anthony Magee

Study with NHLI

What we do

Research in the Molecular Medicine Section encompasses the physiology and pathology of normal cardiovascular and lung function, and of associated disease.  Our expertise includes molecular and cell biology, biochemistry, microscopy, spectroscopy, pharmacology and clinical medicine.  Our broader interests extend to muscle wasting, neurodegenerative disease, cancer, HIV, cardiorespiratory and metabolic disease, and drug discovery.

Why it is important

Our research identifies mechanisms of physiology and disease and provides key underpinning approaches to study heart and lung disease through interdisciplinary collaboration across the National Heart and Lung Institute (NHLI) and beyond. 

Impact of our research

We study a number of biological and pathological processes at the fundamental molecular and cellular level, to understand normal biological function, how it goes wrong in disease and the effect of drug-like molecules.  We use model systems and also human material.  Much of our research will have longer term benefits for human health, but some of it is aimed at having direct short term benefits for patients.

Summary of current research

  • Cell-Cell Adhesion Signalling: We investigate the signalling mechanisms by which epithelial cells adhere to each other and that underpin tissue architecture and function. Such knowledge contributes towards our understanding of cancer cell dissociation and metastasis (Dr Vania Braga).
  • Protein Biophysics: We apply biophysical techniques (including single molecule fluorescence and kinetic methods) to biomedical problems involving proteins. We are currently measuring the dynamics and inhibition of protein kinases in cancer and inflammatory disease, inhibiting the Complement system and developing novel probes of kinase activity (Dr Charlotte Dodson).
  • Platelet Biology: We study the physiological regulation of platelets and investigate cardiovascular risk in relation to pollution and HIV (Dr Mike Emerson).
  • Muscle Gene Expression: We are interested in the epigenetic mechanisms that contribute to chronic and acute muscle wasting. Primarily we focus on the role of microRNAs in the control of muscle cell phenotype during wasting and regeneration (Dr Paul Kemp).
  • Matrix-Activated Receptors:  We are interested in the molecular mechanisms of receptor activation and primarily focus on understanding kinase activation of the discoidin domain receptors, key drug targets in a number of diseases including organ fibrosis, inflammation, osteoarthritis, atherosclerosis and many different types of cancer (Dr Birgit Leitinger).
  • Structure of Muscle Sarcomere: We use cryo-electron microscopy and tomography to understand the 3-dimensional structure of the sarcomere in cardiac and skeletal muscle (Dr Pradeep Luther).
  • Membrane Biology: We study the covalent attachment of lipids to proteins and how they affect function. A current focus is the Hedgehog signalling pathway that is important in normal animal development and cancer (Professor Tony Magee).
  • Skeletal Muscle Plasticity and Metabolism: We focus on the metabolism and phenotype of skeletal muscle, as targets for treating exercise intolerance in patients with chronic diseases such as COPD and for treating type 2 diabetes and obesity (Dr Amanda Natanek).
  • Single Molecule Biophysics: We are developing and applying single molecule spectroscopy and imaging tools to address important questions in cardiovascular and neurodegenerative diseases  (Dr Liming Ying).

Connections

Related Facility

Key publications

Erasmus, J.C., Bruche, S., Pizarro, L., Maimari, N., Pogglioli, T., Tomlinson, C., Lees, J., Zalivina, I., Wheeler, A., Alberts, A., Russo, A. & Braga, V.M.M. (2016). Defining functional interactions during biogenesis of epithelial junctions.  Nature Communications, 7: 13542 | DOI: 10.1038/ncomms13542. 

Dodson, C.A. and Bayliss, R. (2012). Activation of Aurora-A kinase by protein partner binding and phosphorylation are independent and synergistic. J. Biol. Chem., 287: 1150-1157

Solomon, A., Smyth, E., Mitha, N., Pitchford, S., Vydyanath, A., Luther, P.K., Thorley, A.J., Tetley, T.D. and Emerson, M. (2013). Induction of platelet aggregation after direct physical interaction with diesel exhaust particles. J. Thromb. Haemost. 11: 325-34.

Bloch, S.A.A., Lee, J.Y., Syburra, T., Rosendahl, U., Griffiths, M.J.D., Kemp, P.R. and Polkey, M.I. (2015). Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAsTHORAX, 70: 219-228, ISSN: 0040-6376

Xu, H., Bihan, D., Chang, F., Huang, P.H., Farndale, R.W. & Leitinger, B. (2012). Discoidin domain receptors promote α1β1- and α2β1-integrin mediated cell adhesion to collagen by enhancing integrin activation. PLoS ONE 7: e52209.

Burgoyne, T., Morris, E.P. and Luther, P.K. (2015). Three-Dimensional Structure of Vertebrate Muscle Z-Band: The Small-Square Lattice Z-Band in Rat Cardiac Muscle. J. Mol. Biol.  427: 3527–3537. (http://www.sciencedirect.com/science/article/pii/S0022283615004830) 

Rodgers, U., Lanyon-Hogg, T., Masumoto, N., Ritzefeld, M., Burke, R., Blagg, J., Magee, A. and Tate, E. (2016). Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells. ACS Chem. Biol., Oct 25 [Epub ahead of print]. doi: 10.1021/acschembio.6b00896.

Natanek, S.A., Gosker, H.R., Slot, I.G., Marsh, G.S., Hopkinson, N.S., Moxham, J., Kemp, P.R., Schols, A.M. and Polkey, M.I. (2013). Pathways associated with reduced quadriceps oxidative fibres and endurance in COPD. Eur. Respir. J. 41: 1275-83. doi: 10.1183/09031936.00098412.

Branch, T., Girvan, P., Barahona, M. and Ying, L.M. (2015). Introduction of a fluorescent probe to amyloid-β to reveal kinetic insights into its interactions with Copper(II). Angew. Chem. Int. Ed. 54:  1227-1230.


Our researchers