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Prof Michael Duchen

  • Telephone:

    020 7679 3207

  • Extension:

    33207

  • Email:

    m.duchen@ucl.ac.uk

  • Webpage:

    http://www.ucl.ac.uk/cdb/research/duchen

  • Address:

    Cell and Developmental Biology, University College London,
    Gower Street,
    London,
    WC1E 6BT

  • Appointments:

    Professor of Physiology, Cell & Developmental Biology, Div of Biosciences

Summary

Born in South Africa, moving to the UK in 1960. Studied Physiology and Medicine in Oxford, 1971-75, then moved to St George's Hospital Medical School to complete clinical training, graduating 1978. Worked in clinical medicine in junior hospital appointments 1978-1981 including a period working at a rural hospital in the Transkei, South Africa. Moved to UCL to embark on PhD studies 1981 -1984 with Tim Biscoe as supervisor and mentor. Have stayed at UCL Physiology ever since.

 

Research Summary

We are interested in a wide range of issues related to mitochondrial biology and cell signaling. Much of our current work is focused on interrelationships between calcium signaling, mitochondria and free radicals in cell physiology and pathophysiology. This work embraces questions about thecontributions of mitochondrial function to intracellular calcium signaling.

We are fascinated by the intimate dialogue between mitochondrial biology and cell signaling systems. How do cell signaling pathways impact on and regulate mitochondrial physiology? How do subtle changes in mitochondrial function affect the physiology of the cell? How are mitochondria in different cell types specialized to match the specialized differentiated function of the cells they inhabit? We are especially concerned to characterise the contributions of mitochondrial dysfunction to cell injury and cell death - by necrosis or apoptosis – that takes place in situations such as ischaemia, reperfusion injury and in the neurotoxicity mediated by glutamate or beta-amyloid. Another core theme again involving a complex dialogue is the mitochondrion as both a site and a target of oxidative stress and damage in disease models. Most of our work involves live cell fluorescence microscopy and imaging, including confocal, multiphoton and fast read-out cooled CCD instruments. All approaches have been adapted to allow the simultaneous or near simultaneous measurement of multiple variables - cytosolic calcium and mitochondrial potential, cytosolic calcium and mitochondrial calcium, NADH autofluorescence and cytosolic calcium or cytosolic magnesium and so on. 

We have a broad general interest in functional cellular imaging and in the development of new approaches to imaging aspects of cell function usingtargeted probes, GFP tagged proteins, FRET, FLIM and so on. 
Interests of the lab extend through a wide range of biological problems in which mitochondria are involved - in ischaemia reperfusion injury in the heart, in the role of mitochondrial function in fertility in the  mammalian egg (with John Carroll), in mitochondrial function and septic shock syndrome in liver, kidney and muscle, in mitochondrial biogenesis following exercise and training in muscle, and in mitochondrial dysfunction in beta cells in diabetes. This rather unusual breadth has had a positive influence on all our work, as resolving problems in one system invariably seems to illuminate problems with others. We have been astonished at the frequency with which a small number of basic principles are recapitulated in a wide and disparate array of models. 

For recent reviews, see: 





Research Activities

  • A systematic investigation into the pathogenesis and course of Parkinson's syndrome
  • Autonomic neuroscience
  • Calcium signalling and mitochondrial function in cell physiology and pathophysiology.
  • Cell signalling
  • Intracellular and intercellular signalling mechanisms in health and disease
  • Paediatric Neurology
  • Regulation and targeting of the hypoxia inducible factor (HIF) pathway
  • The central nervous system regulation of energy homeostasis
  • The neurogenetics of neurodegenerative disease
  • The role of mitochondria in cardioprotection
  • critical care

Recent Publications

Displaying 50 most recent publications. For the full list please visit UCL Discovery

  1. Osellame LD,Rahim AA,Hargreaves IP,Gegg ME,Richard-Londt A,Brandner S,Waddington SN,Schapira AHV,Duchen MR (2013) Mitochondria and quality control defects in a mouse model of Gaucher disease - links to Parkinson’s Disease Cell Metabolism.
  2. Corona JC,Duchen MR (2013) Rosiglitazone protects human neuron-like cells against complex I inhibition through improvement of mitochondrial function JOURNAL OF NEUROCHEMISTRY, 125, 177 - 178.
  3. Faccenda D,Tan CH,Seraphim A,Duchen MR,Campanella M (2013) IF1 limits the apoptotic-signalling cascade by preventing mitochondrial remodelling. Cell Death Differ, 20(5), 686 - 697. 10.1038/cdd.2012.163.
  4. Chlystun M,Campanella M,Law AL,Duchen MR,Fatimathas L,Levine TP,Gerke V,Moss SE (2013) Regulation of mitochondrial morphogenesis by annexin A6. PLoS One, 8(1), e53774. 10.1371/journal.pone.0053774.
  5. Munteanu I,Zhou H,Hargreaves I,Yasukawa T,Duchen MR,Muntoni F (2012) Investigating mitochondria in cell culture models of core myopathies NEUROMUSCULAR DISORDERS, 22, S30 - S30.
  6. Girard M,Larivière R,Parfitt DA,Deane EC,Gaudet R,Nossova N,Blondeau F,Prenosil G,Vermeulen EG,Duchen MR,Richter A,Shoubridge EA,Gehring K,McKinney RA,Brais B,Chapple JP,McPherson PS (2012) Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Proc Natl Acad Sci U S A, 109(5), 1661 - 1666. 10.1073/pnas.1113166109.
  7. Davidson SM,Yellon DM,Murphy MP,Duchen MR (2012) Slow calcium waves and redox changes precede mitochondrial permeability transition pore opening in the intact heart during hypoxia and reoxygenation. Cardiovasc Res, 93(3), 445 - 453. 10.1093/cvr/cvr349.
  8. Davidson SM,Duchen MR (2012) Imaging mitochondrial calcium signalling with fluorescent probes and single or two photon confocal microscopy. Methods Mol Biol, 810, 219 - 234. 10.1007/978-1-61779-382-0_14.
  9. Traba J,Del Arco A,Duchen MR,Szabadkai G,Satrústegui J (2012) SCaMC-1 promotes cancer cell survival by desensitizing mitochondrial permeability transition via ATP/ADP-mediated matrix Ca(2+) buffering. Cell Death Differ, 19(4), 650 - 660. 10.1038/cdd.2011.139.
  10. Duchen MR (2012) Mitochondria, calcium-dependent neuronal death and neurodegenerative disease. Pflugers Arch, 464(1), 111 - 121. 10.1007/s00424-012-1112-0.
  11. Gandhi S,Vaarmann A,Yao Z,Duchen MR,Wood NW,Abramov AY (2012) Dopamine induced neurodegeneration in a PINK1 model of Parkinson's disease. PLoS One, 7(5), e37564. 10.1371/journal.pone.0037564.
  12. Papkovskaia TD,Chau KY,Inesta-Vaquera F,Papkovsky DB,Healy DG,Nishio K,Staddon J,Duchen MR,Hardy J,Schapira AH,Cooper JM (2012) G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization. Hum Mol Genet, 21(19), 4201 - 4213. 10.1093/hmg/dds244.
  13. Ding S,Riddoch-Contreras J,Abramov AY,Qi Z,Duchen MR (2012) Erratum to: Mild stress of caffeine increased mtDNA content in skeletal muscle cells: the interplay between Ca(2+) transients and nitric oxide. J Muscle Res Cell Motil, 33(5), 339. 10.1007/s10974-012-9327-4.
  14. Ding S,Riddoch-Contreras J,Abramov AY,Qi Z,Duchen MR (2012) Mild stress of caffeine increased mtDNA content in skeletal muscle cells: the interplay between Ca2+ transients and nitric oxide. J Muscle Res Cell Motil, 33(5), 327 - 337. 10.1007/s10974-012-9318-5.
  15. Abeti R,Duchen MR (2012) Activation of PARP by oxidative stress induced by β-amyloid: implications for Alzheimer's disease. Neurochem Res, 37(11), 2589 - 2596. 10.1007/s11064-012-0895-x.
  16. Schwarzländer M,Murphy MP,Duchen MR,Logan DC,Fricker MD,Halestrap AP,Müller FL,Rizzuto R,Dick TP,Meyer AJ,Sweetlove LJ (2012) Mitochondrial 'flashes': a radical concept repHined. Trends Cell Biol, 22(10), 503 - 508. 10.1016/j.tcb.2012.07.007.
  17. Osellame LD,Rahim A,Gegg ME,Waddington S,Schapira AHV,Duchen MR (2012) Accumulation of damaged mitochondria in neuropathic Gaucher disease, the most prevalent risk factor for Parkinson's disease, is due to defective cellular degradation machinery BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1817, S79 - S80. 10.1016/j.bbabio.2012.06.217.
  18. Corona JC,Duchen MR (2012) Rosiglitazone protects differentiated SH-SY5Y cells against damage induced by rotenone through mitochondrial biogenesis and by anti-oxidative mechanisms BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1817, S68 - S68. 10.1016/j.bbabio.2012.06.192.
  19. Osellame LD,Blacker TS,Duchen MR (2012) Cellular and molecular mechanisms of mitochondrial function. Best Pract Res Clin Endocrinol Metab, 26(6), 711 - 723. 10.1016/j.beem.2012.05.003.
  20. Abramov AY,Duchen MR (2011) Measurements of threshold of mitochondrial permeability transition pore opening in intact and permeabilized cells by flash photolysis of caged calcium. Methods Mol Biol, 793, 299 - 309. 10.1007/978-1-61779-328-8_19.
  21. Abramov AY,Ionov M,Pavlov E,Duchen MR (2011) Membrane cholesterol content plays a key role in the neurotoxicity of β-amyloid: implications for Alzheimer's disease. Aging Cell, 10(4), 595 - 603. 10.1111/j.1474-9726.2011.00685.x.
  22. Hall AM,Crawford C,Unwin RJ,Duchen MR,Peppiatt-Wildman CM (2011) Multiphoton imaging of the functioning kidney. J Am Soc Nephrol, 22(7), 1297 - 1304. 10.1681/ASN.2010101054.
  23. Abeti R,Abramov AY,Duchen MR (2011) Beta-amyloid activates PARP causing astrocytic metabolic failure and neuronal death. Brain, 134(Pt 6), 1658 - 1672. 10.1093/brain/awr104.
  24. Duchen MR,Heath K,Baruch NB,Hanna MG,Muntoni F (2011) Dysregulation of calcium and mitochondrial function as potential therapeutic targets in muscle disease NEUROMUSCULAR DISORDERS, 21, S1 - S2.
  25. Munteanu I,Yasukawa T,Duchen MR,Muntoni F (2010) Uncovering the role of mitochondria in the pathogenesis of core myopathies NEUROMUSCULAR DISORDERS, 20, S24 - S24.
  26. Traba J,Amigo I,Rueda C,Szabadkai G,Duchen MR,Satrustegui J,del Arco A (2010) The Ca2+-dependent ATP-Mg/Pi carriers as novel regulators of the mitochondrial permeability transition pore BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1797, 130 - 130. 10.1016/j.bbabio.2010.04.386.
  27. Ahluwalia J,Tinker A,Clapp LH,Duchen MR,Abramov AY,Pope S,Nobles M,Segal AW (2010) The large-conductance Ca2+-activated K+ channel is essential for innate immunity (Retraction of vol 427, pg 853, 2004) NATURE, 468(7320), 122 - 122. 10.1038/nature09562.
  28. El-Kadi AM,Bros-Facer V,Deng W,Philpott A,Stoddart E,Banks G,Jackson GS,Fisher EM,Duchen MR,Greensmith L,Moore AL,Hafezparast M (2010) The legs at odd angles (Loa) mutation in cytoplasmic dynein ameliorates mitochondrial function in SOD1G93A mouse model for motor neuron disease. J Biol Chem, 285(24), 18627 - 18639. 10.1074/jbc.M110.129320.
  29. Ng KE,Schwarzer S,Duchen MR,Tinker A (2010) The intracellular localization and function of the ATP-sensitive K+ channel subunit Kir6.1. J Membr Biol, 234(2), 137 - 147. 10.1007/s00232-010-9241-x.
  30. Duchen MR,Szabadkai G (2010) Roles of mitochondria in human disease. Essays Biochem, 47, 115 - 137. 10.1042/bse0470115.
  31. Abramov AY,Smulders-Srinivasan TK,Kirby DM,Acin-Perez R,Enriquez JA,Lightowlers RN,Duchen MR,Turnbull DM (2010) Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations. Brain, 133(Pt 3), 797 - 807. 10.1093/brain/awq015.
  32. Hall AM,Campanella M,Loesch A,Duchen MR,Unwin RJ (2010) Albumin uptake in OK cells exposed to rotenone: a model for studying the effects of mitochondrial dysfunction on endocytosis in the proximal tubule? Nephron Physiol, 115(2), p9 - p19. 10.1159/000314540.
  33. Igosheva N,Abramov AY,Poston L,Eckert JJ,Fleming TP,Duchen MR,McConnell J (2010) Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS One, 5(4), e10074. 10.1371/journal.pone.0010074.
  34. Averaimo S,Milton RH,Duchen MR,Mazzanti M (2010) Chloride intracellular channel 1 (CLIC1): Sensor and effector during oxidative stress. FEBS Lett, 584(10), 2076 - 2084. 10.1016/j.febslet.2010.02.073.
  35. Abramov AY,Duchen MR (2010) Impaired mitochondrial bioenergetics determines glutamate-induced delayed calcium deregulation in neurons. Biochimica et Biophysica Acta (BBA) - General Subjects. 10.1016/j.bbagen.2009.08.002.
  36. Gandhi S,Wood-Kaczmar A,Yao Z,Plun-Favreau H,Deas E,Klupsch K,Downward J,Latchman DS,Tabrizi SJ,Wood NW,Duchen MR,Abramov AY (2009) PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death Molecular Cell, 33(5), 627 - 638. 10.1016/j.molcel.2009.02.013.
  37. Szabadkai G,Duchen MR (2009) Mitochondria mediated cell death in diabetes. Apoptosis. 10.1007/s10495-009-0363-5.
  38. Campanella M,Seraphim A,Abeti R,Casswell E,Echave P,Duchen MR (2009) IF1, the endogenous regulator of the F(1)F(o)-ATPsynthase, defines mitochondrial volume fraction in HeLa cells by regulating autophagy. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1787(5), 393 - 401. 10.1016/j.bbabio.2009.02.023.
  39. Cantley J,Selman C,Shukla D,Abramov AY,Forstreuter F,Esteban MA,Claret M,Lingard SJ,Clements M,Harten SK,Asare-Anane H,Batterham RL,Herrera PL,Persaud SJ,Duchen MR,Maxwell PH,Withers DJ (2009) Deletion of the von Hippel-Lindau gene in pancreatic beta cells impairs glucose homeostasis in mice. Journal of Clinical Investigation, 119(1), 125 - 135. 10.1172/JCI26934.
  40. Echave P,Machado-da-Silva G,Arkell RS,Duchen MR,Jacobson J,Mitter R,Lloyd AC (2009) Extracellular growth factors and mitogens cooperate to drive mitochondrial biogenesis. Journal of Cell Science, 122(24), 4516 - 4525.
  41. Dumollard R,Carroll J,Duchen MR,Campbell K,Swann K (2009) Mitochondrial function and redox state in mammalian embryos. Seminars in Cell and Developmental Biology, 20(3), 346 - 353.
  42. Hall AM,Unwin RJ,Parker N,Duchen MR (2009) Multiphoton imaging reveals differences in mitochondrial function between nephron segments. Journal of the American Society of Nephrology, 20(6), 1293 - 1302.
  43. Campanella M,Parker N,Tan CH,Hall AM,Duchen MR (2009) IF(1): setting the pace of the F(1)F(o)-ATP synthase. Trends in Biochemical Sciences.
  44. Galkin A,Abramov AY,Frakich N,Duchen MR,Moncada S (2009) Lack of oxygen deactivates mitochondrial complex I: implications for ischemic injury? J Biol Chem, 284(52), 36055 - 36061. 10.1074/jbc.M109.054346.
  45. Wood-Kaczmar A,Gandhi S,Yao Z,Abramov AY,Miljan EA,Keen G,Stanyer L,Hargreaves I,Klupsch K,Downward J,Mansfield L,Jat P,Taylor J,Heales S,Duchen MR,Latchman D,Tabrizi SJ,Wood NW (2009) PINK1 is necessary for long term survival and mitochondrial function in primary human dopaminergic neurons JOURNAL OF NEUROCHEMISTRY, 109, 301 - 302.
  46. Gandhi S,Wood-Kaczmar A,Wood NW,Duchen MR,Abramov AY (2009) PINK1 associated Parkinson's disease is caused by neuronal vulnerability to calcium induced cell death MOVEMENT DISORDERS, 24, S33 - S33.
  47. Mann ZF,Duchen MR,Gale JE (2009) Mitochondria modulate the spatio-temporal properties of intra- and intercellular Ca2+ signals in cochlear supporting cells. Cell Calcium, 46(2), 136 - 146. 10.1016/j.ceca.2009.06.005.
  48. Zolfaghari P,Singer M,Duchen MR (2009) UNCOUPLING PROTEIN-3 MEDIATES THE LOSS OF MITOCHONDRIAL MEMBRANE POTENTIAL IN SEVERE SEPSIS INTENSIVE CARE MEDICINE, 35, 164 - 164.
  49. Milton RH,Abeti R,Averaimo S,DeBiasi S,Vitellaro L,Jiang L,Curmi PM,Breit SN,Duchen MR,Mazzanti M (2008) CLIC1 function is required for beta-amyloid-induced generation of reactive oxygen species by microglia. J Neurosci, 28(45), 11488 - 11499. 10.1523/JNEUROSCI.2431-08.2008.
  50. Szabadkai G,Duchen MR (2008) Mitochondria: the hub of cellular Ca2+ signaling. Physiology (Bethesda), 23(2), 84 - 94.

Biography

Born in South Africa, moving to the UK in 1960. Studied Physiology and Medicine in Oxford, 1971-75, then moved to St George's Hospital Medical School to complete clinical training, graduating 1978. Worked in clinical medicine in junior hospital appointments 1978-1981 including a period working at a rural hospital in the Transkei, South Africa. Moved to UCL to embark on PhD studies 1981 -1984 with Tim Biscoe as supervisor and mentor. Have stayed at UCL Physiology ever since.

 

Qualifications

  • 1984: Doctor of Philosophy, University College London
  • 1981: Member of the Royal College of Physicians,
  • 1978: Bachelor of Medicine/Bachelor of Surgery, St George's Hospital Medical School
  • 1975: Bachelor of Arts, University of Oxford

Keywords

  • Alzheimer's disease
  • Amyloid
  • Calcium
  • Calcium imaging
  • Confocal microscopy
  • Dementia
  • Demyelination
  • Fluorescence microscopy techniques
  • Genetic manipulation (including knockout/knockin)
  • Genetically encoded reporters/indicators
  • Imaging
  • Ischaemic stroke
  • Light microscopic techniques
  • Metabolic myopathies
  • Mitochondria
  • Mitochondria in cell physiology and disease
  • Mitochondrial encephalomyopathies
  • Motor Neurone Disease
  • Mouse
  • Multi-photon imaging
  • Multiple Sclerosis
  • Neurodegeneration
  • Neurodegenerative diseases
  • Neuron
  • Nitric oxide
  • Parkinson's disease
  • Stroke
  • Transgenic mice
  • Voltage-sensitive dyes