Department: Comparative Biomedical Sciences
Research Centres: Imaging Suite
Michelangelo is currently holding a position of Reader in Pharmacology and is affiliated Principal Investigator to the Consortium for Mitochondrial Research (UCL) http://www.ucl.ac.uk/mitochondria/.
Focus of his research activity is to assess the functional role molecules in respect of the regulation of key mitochondrial enzymatic pathways and in the experimentation of strategies to target them and define novel pharmacological treatments. See relative section for more details and the personal website: www.michelangelocampanella.com
Michelangelo (known as Miche) studied in Italy at the School of Pharmacy of the University of Ferrara where he obtained a degree as Doctor of Pharmacy. The course focused on the knowledge and clinical usage of therapeutics and the comprehension of their pharmacological basis and protocols of preparation.
In the last two years of his degree, Michelangelo joined the lab of Professor Rosario Rizzuto to undertake his undergraduate research project focused on the development and learning of luminescence based approaches to monitor Ca2+ and ATP signals in living cells. Prof. Rizzuto is one of the world experts in Ca2+ signalling who also has the merit of identifying mitochondria as a relevant pathway for the definition of Ca2+ homeostasis.
Michelangelo has also worked at the Columbia University of New York in the lab of Professor Eric Schon, a luminary figure engaged in the clarification of the mitochondrial genetic, who taught him the principles and the basal techniques of molecular biology.
Upon completion of his degree, Michelangelo registered to the Italian Pharmaceutical Society to practise as a Pharmacist.
Following a short period in practice, he began a PhD in Cellular and Molecular Pharmacology still under the supervision of Prof. Rizzuto. His PhD work was centred on the role of Ca2+ in programmed cell death. After concluding his PhD, Michelangelo was keen to undertake further training so he moved abroad and joined the lab of Professor Michael R Duchen at the University College London. Prof. Duchen is an eminent scientist renowned for his work on mitochondrial physiology and his unique competence of imaging techniques.
During his period at UCL Michelangelo received initial support from the Royal Society, Accademia dei Lincei and the European Molecular Biology Organization (EMBO) before being awarded of a Marie Curie Intra-European Fellowship which allowed him to complete a research period lasting 3 years. During this time he was also honoured of the opportunity to attend the Lindau meeting of Nobel prizes in Physiology as a young promising scientist in the field.
Michelangelo moved to the RVC Department of Comparative Biomedical Sciences in February 2008 where he holds a position of Reader in Pharmacology and since June 2009 he has mecome also member of the Consortium for Mitochondrial research (CfMR) of the University College London as Affiliated Group Leader.
He is currently serving in various editorial boards and roles (e.g. Cell Death and Disease, Autophagy, Frontiers, Biochemical Journal, Current Molecular Medicine and Pharmacological Research). More recently, for the constant engagement in relevant topics, he has been also named Local Ambassador of the Biochemical Society.
In the recent years, the research activity of Dr Campanella and his collaborators has been dedicated to investigate fundamental concepts associated with the biology and pharmacology of mitochondria lying at the basis of the whole cellular health: ENERGY and QUALITY. PATHWAYS and MOLECULES which concomitantly impinge on both these aspects have been therefore objectives of his investigation aiming to provide information of vital aspects of normal and abnormal cell function.
Homeostasis of cells and tissues depends on the fine balance between energy and quality. In modern experimental cell biology there is currently considerable interest in the physiology and pathology of the intracellular primary sources of energy - the mitochondria - and the biological processes preserving homeostasis and maintaining a supply of nutrients, such as autophagy.
In the last decades, revolutionary discoveries on physiology and pathology of mitochondria have been this one of the most dynamic and exciting field in modern biomedical research spanning from regulation of oxidative phosphorylation, till mechanisms of their morphology and movement and key role in cell signalling and programmed cell death.
Various are the medical conditions caused or contributed by defective mitochondrial function. Besides the genetic diseases of mitochondrial origin, our ultimate goal is to address the mechanisms underlying unhealthy Ageing and do so by studying maladaptation of mitochondrial function to epigenetic conditions such as Neurodegeneration and Cancer.
In these aspects we take great advantage of a comparative approach that lets us achieve in vivo evidences useful to refine pharmacological approaches.
Topics of Interest are therefore:
Bioenergetics of Mitochondrial Quality Control (Mitophagy)
Preservation of mitochondrial integrity is highly dependent on the regulatory autophagy processes, which target and eliminate dysfunctional mitochondria. This system, known as mitophagy, is paramount for cellular well being in order to overcome respiratory deficiency.
Mitochondrial Pharmacology and Targeting
Although fundamental to the regulation of cell biology, mitochondria seem neglected, or just partially exploited, therapeutic targets. Therapies designed to prevent mitochondrial dysfunction could be thus beneficial and implemented to treat various life-debilitating and life-threatening conditions.
Pathways of Immediate Interest are:
The 18-KDa Mitochondrial Translocator Protein (TSPO)
The F1Fo-ATPsynthase Inhibitor Factor (IF1)
Current Lab Members
The research unit directed by Dr Campanella is composed of young and talented scientists:
Dr. Daniel East, PostDoc
Dr. Jemma Gatliff, PostDoc
Dr. Rebeca Martin-Jimenez, PostDoc
Dr. Ivana Matic, PosDoc
Dr. Daniela Strobbe, PostDoc
Mr Danilo Faccenda, PhDStudent
Mr Michele Frison, PhD Student
Mr Nikolaos Georgakopoulos, PhD Student
Ms Caterina Ferraina, Research Assistant
A long lasting collaboration of the Dr Campanella is with Prof. Michael R Duchen, Head of the CfMR UCL, whilst other ongoing collaborative work is with colleagues at the UCL Institute of Child Health in the person of Prof. Paolo de Coppi, at the Institute of Neurology with Prof. Andrey Y Abramov and Prof. Kenneth Smith and at the School of Pharmacy with Dr Geoff Wells and Prof. Robert J Harvey.
Other prominent collaborative work is with Prof. Federico Turkheimer of the King's College Centre for Neuroimaging Sciences, Institute of Psychiatry and Dr. William Trigg of the GE Health Care on the topic of TSPO and neuroinflammation.
Miche holds also an Honorary Professorship Appointment at the Department of Biology of the University of Rome TorVergata linked with the Regina-Elena National Cancer Institute which allows him to follow a collaborative research program with leaders in the field of Autophagy, Apoptotic Cell Death and Tumors genesis and progression with leaders in the field such as Prof. Mauro Piacentini, Prof. Francesco Cecconi and Prof. Ruggero De Maria.
Numerous are the intramural links with colleagues leading the niches of expertise that make RVC a renown center of excellence for investigation in the fields of Comparative Cancer Biology (Prof. Ken Smith), Bone Biology (Prof. Andy Pitsillides) and Equine pathology (Prof. Richard Piercy). Together with Dr. Claire Russell an active joint effort to maximize the exploitation of the Zebrafish as model alternative to the mammalian system to define in vivo mechanisms of pathology and potential therapeutic strategies is being pursued.
His research activity is prevalently supported by the BBSRC, MRC, PPCT, SPARKS and Marie Curie Actions.
1. Jemma Gatliff and Michelangelo Campanella. TSPO is a REDOX regulator of Cell Mitophagy. Biochemical Transactions in press
2. Campanella M, TSPO the unrested: challenged opinions of a resourceful mitochondrial protein. Trends Endocrinol Metab. 2015 Jul;26(7):333-4
3. Rebeca Martin-Jimenez, Michelangelo Campanella and Claire Russell. Neuroscience Catch Of The Day: Zebrafish models of neurodegeneration. Curr Neurol Neurosci Rep. 2015 Jun;15(6):33. doi: 10.1007/s11910-015-0555-z
4. Ivana Matic, Strobbe Daniela, Michele Frison and Michelangelo Campanella. Control and impairment of Mitochondrial Quality in Neurons. Pharmacol Res. 2015 Apr 23. pii: S1043-6618(15)00060-2. doi: 10.1016
5. Galluzzi L, ….Campanella M,…..Kroemer G, Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ. 2015 Jan;22(1):58-73. doi: 10.1038/cdd.2014.137.
6. Gatliff, East D, Crosby J, Abeti R Harvey R, Craigen W, Parker P and Campanella M. TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control. Autophagy 2014 Dec 2;10(12):2279-96. doi: 10.4161/15548627.2014.991665.
7. East D, Fagiani F, Crosby J, Bertrand H, Schaap M, Fowkes A, Wells G, and Campanella M. PMI: a novel, ΔΨm independent, Mitophagy Inducer”. Chem Biol. 2014 Nov 20;21(11):1585-96. doi: 10.1016/j.chembiol.2014.09.019.
8. Campanella M. Peptide targeting of mitochondria elicits testosterone formation.
Mol Ther. 2014 Oct;22(10):1727-9. doi: 10.1038/mt.2014.171.
9. Altuntas S, D'Eletto M, Rossin F, Farrace MG, Falasca L, Piredda L, Cocco S, Piacentini M and Campanella M. Transglutaminase Type 2, Mitochondria and Huntington's Disease: Menage a trois. Mitochondrion 2014 Nov;19 Pt A:97-104. doi: 10.1016/j.mito.2014.09.008.
10. Strappazzon F, Nazio F, Corrado M, Cianfanelli V, Romagnoli A, Fimia GM, Campello S, Nardacci R, Piacentini M, Campanella M, Cecconi F. Cell Death Differ. 2014 Sep 12. doi: 10.1038/cdd.2014.139.
11. Rossin F, D'Eletto M, Falasca L, Sepe S, Cocco S, Fimia GM, Campanella M, Mastroberardino PG, Farrace MG, Piacentini M. Transglutaminase 2 ablation leads to mitophagy impairment associated with a metabolic shift towards aerobic glycolysis. Cell Death Differ. 2014 Jul 25. doi: 10.1038/cdd.2014.106.
12. Ivanes, F, Allan E, Faccenda D, Ahmed AA, Gatliff J, Russell C, Duchen MR and Campanella M. The Chemical Agent BTB06584 Targets the Reversion of the Mitochondrial F1Fo-ATPsynthase mimicking IF1. Br J Pharmacol. 2014 Feb 15. doi: 10.1111/bph.12638
13. Archacka K, Pozzobon M, Repele A, Rossi CA, Campanella M and De Coppi P. Culturing muscle fibers in hanging drops: a novel approach to solve an old problem. Biol Cell. 2014 Feb;106(2):72-82. doi: 10.1111/boc.201300028.
14. Amadoro G, Corsetti N, Florenzano F, Atlante A, Ciotti MT, Mongiardi MP, Bussani R, Nicolin V, Nori SL, Campanella M, Calissano P. AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons. Neurobiol Dis. 2014 Feb;62:489-507. doi: 10.1016/j.nbd.2013.10.018.
15. Campanella M, Klionsky DJ. Keeping the engine clean: A mitophagy task for cellular physiology. Autophagy. 2013 22;9(11).
16. East D and Campanella M. Ca2+ in quality control: an unresolved riddle critical to autophagy and mitophagy. Autophagy 2013 22;9(11).
17. Lefebvre V, Du Q, Bair S, Cheuk-Him Ng A, Eric Shoubridge, Campanella M, McBride HM, Screaton RA. The ATPase Inhibitory Factor 1 (IF1) is required for PARKIN recruitment to mitochondria and mitophagy. Autophagy. 2013 22;9(11).
18. Faccenda D, Tan CH, Duchen MR, Campanella M. Mitochondrial IF 1 preserves cristae structure to limit apoptotic cell death signaling. Cell Cycle. 2013 15;12(16):2530-2. doi: 10.4161/cc.25840.
19. Iannetti L, Abbouda A, Fabiani C, Zito R, Campanella M. Treatment of corneal neovascularization in ocular chemical injury with an off-label use of subconjunctival bevacizumab: a case report. J Med Case Rep. 2013 26;7(1):199. doi: 10.1186/1752-1947-7-199.
20. Repele A, Lupi R, Eaton S, De Coppi P and Campanella M. Fundamental Cell Biology sets the Differences between Subpopulations of Satellite Cells (SCs). BMC Cell Biol. 2013 3;14(1):24.
21. Chlystun M, Campanella M, Law A, Duchen MR, Fatimathas L, Levine T, GerkeV, Moss S. Regulation of Mitochondrial Morphogenesis by Annexin A6. Plos One 2013;8(1):e53774. doi:10.1371/journal.pone.005377
22. Vara DS, Campanella M, Dunn WB, Pizzorno G, Hirano M, Pula G. Autocrine amplification of integrin αIIbβ3 activation and platelet adhesive responses by deoxyribose-1- phosphate. Thromb Haemost. 2013 14;109(5).
23. Faccenda D, Tan CH, Seraphim A, Duchen MR & Campanella M. The F1Fo-ATPase endogenous inhibitor IF1 regulates Mitochondrial Commitment to Apoptosis. Cell Death Differ. 2013;20(5):686-97. doi: 10.1038/cdd.2012.163.
24. Shah DI, Takahashi-Makise N, Cooney JD, Li L, Schultz IJ, Pierce EL, Narla A, Seguin A, Hattangadi SM, Medlock AE, Langer NB, Dailey TA, Hurst SN, Faccenda D, Wiwczar JM, Heggers SK, Vogin G, Chen W, Chen C, Campagna DR, Brugnara C, Zhou Y, Ebert BL, Danial NN, Fleming MD, Ward DM, Campanella M, Dailey HA, Kaplan J, Paw BH. Mitochondrial Atpif1 regulates heme synthesis in developing erythroblasts. Nature. 2012 22;491(7425):60812.
25. Iannetti L, Paroli MP, Fabiani C, Campanella M, Pivetti-Pezzi P. Effects of Intravitreal Bevacizumab on Inflammatory Choroidal Neovascular Membrane. Eur J Ophthalmol. 2012 8:0. doi: 10.5301/ejo.5000192.
26. Klionsky DJ ...Campanella M....Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy. Autophagy. 2012 8(4):445-544.
27. Faccenda D and Campanella M. Molecular Regulation of the Mitochondrial F1Fo ATPsynthase: Physiological and Pathological Significance of the Inhibitor Factor 1 (IF1). Int J Cell Biol. 2012;2012:367934.
28. Campanella, M. Neurodegeneration abides by the laws of Mitochondrial Biology. 2012 European Journal of Neurodegenerative Diseases Vol. 1, No 2, 2012.
29. Varaa DS, Campanella M and Pula G. The NOX1-selectiveinhibitor 2-acetylphenothiazine inhibits superoxide ion generation in human platelets and impairs collagen- dependent thrombus formation. Br J Pharmacol. 2013 168(1):212-24. doi: 10.1111/j.14765381.2012.02130.
30. Plun Favreau H, Burchell VS, Holmstro¨m KM, Yao Z, Deas E, Cain K, Fedele V, Moisoi N, Campanella M, Miguel Martins L, Wood NW, Gourine AV, Abramov AY HtrA2 deficiency causes mitochondrial uncoupling through the F1F0-ATPsynthase and consequent ATP depletion. Cell Death and Disease. 2012 28;3:e335.
31. Galavotti S, Bartesaghi S, Faccenda D, Shaked-Rabi M, Sanzone S, McEvoy A, Dinsdale D, Condorelli F, Brandner S, Tulchinsky E, Grose R, Campanella M, Jones C, Salomoni P. The autophagy associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells. Oncogene. 2013 7;32(6):699-712. doi: 10.1038/onc.2012.111. Epub 2012 Apr 23.
32. Gatliff J and Campanella M. The 18Kda Translocator Protein (TSPO): a New Perspective in Mitochondrial Biology. Curr Mol Med. 2012 12(4):356-68.
33. Severinatne M, Faccenda D, De Biase V & Campanella M. In Bcl-2 knock-down cells, PK11195 inhibits mitophagy targeting the F1Fo-ATPsynthase. Curr Mol Med. 2012 12(4):476-82.
34. Campanella M. The Physiology and Pharmacology of the mitochondrial 18-Kd Translocator Protein (TSPO): an Emerging Molecular Target for Diagnosis and Therapy. Curr Mol Med. 2012;12(4):355.
35. Iannetti L, Accorinti M, Malagola R, Bozzoni-Pantaleoni F, Da Dalt S, Nicoletti F, Gradini R, Traficante A, Campanella M, Pivetti-Pezzi P. Role of the intravitreal growth factors in the pathogenesis of idiopathic epiretinal membrane. Invest Ophthalmol Vis Sci. 2011 52:57869 PMID: 21693611.
36. Pula G, Garonna E, Dunn WB, Hirano M, Pizzorno G, Campanella M, Schwartz EL, El Kouni MH, Wheeler-Jones CP. Arteriosclerosis, Thrombosis, and Vascular Biology. 2010;30(12):26318.
37. Gastaldello A, Gami P, Callaghan H & Campanella M. Ca2+ dependent autophagy is enhanced by the Pharmacological Agent PK11195. Autophagy July 6;6(5). 2010.
38. Hall A, Campanella M, Loesch A, Duchen M, and Unwin R. “Albumin endocytosis in OK cells exposed to rotenone: an ''OKay'' model for the effects of mitochondrial dysfunction on the proximal tubule?" Nephron Physiol. 12;115(2) 2010.
39. Pavlov E, Aschar-Sobbi R, Campanella M, Turner RJ, Gomez-Garcia MR, Abramov AY. Inorganic polyphosphate and energy metabolism in mammalian cells. J Biol Chem 2010 Mar 26;285(13):9420-8.
40. Rossi CA, Pozzobon M, Ditadi A, Archacka K, Gastaldello A, Sanna M, Franzin C, Malerba A, Milan G, Cananzi M, Schiaffino S, Campanella M*, Vettor R, De Coppi P. Clonal characterization of muscle satellite cells: proliferation, metabolism and differentiation define an intrinsic heterogeneity. Plos One 2010 1;5(1):e8523. *Corresponding/Senior author.
41. Ferrari D#, Pinton P#, Campanella M#*, Callegari MG, Pizzirani C, Rimessi A, Di Virgilio F, Pozzan T, Rizzuto R.. Functional and structural alterations in the Endoplasmic Reticulum and mitochondria during apoptosis triggered by C2-ceramide and CD95/APO-1/FAS receptor stimulation. Biochem Biophys Res Commun. 2010 Jan 1;391(1):575-81. #Equally contributed;*Corresponding author.
42. Campanella M, Parker N, Tan CH, Hall AM and Duchen MR. IF1: setting the pace of the F1Fo-ATPsynthase. Trends Biochem Sci. 2009 Jul;34(7):343-50. doi: 10.1016/j.tibs.2009.03.006. Epub 2009 Jun 24. Review.
43. Campanella M, Seraphim A, Abeti R, Casswell E, Echave P, Duchen MR. IF1, the endogenous regulator of the F(1)F(o)-ATPsynthase, defines mitochondrial volume fraction in HeLa cells by regulating autophagy. Biochim Biophys Acta. 2009 May;1787(5):393-401. doi: 10.1016/j.bbabio.2009.02.023. Epub 2009 Mar 5
44. Campanella M*, Szabadkai G and Rizzuto R. Modulation of Intracellular Ca2+ Signalling in HeLa Cells by the Apoptotic Cell Death Enhancer PK11195. Biochemical Pharmacology 2008 1;76(11):1628-36. *Corresponding author.
45. Campanella M, Farah Z, Casswell E, Chong S, Wieckowski MR, Abramov AY, Tinker A and Duchen MR. 2008. Regulation of Mitochondrial Structure and Function by the F(1)F(o)-ATPase Inhibitor Protein, IF(1). Cell Metabolism 2008 Jul;8(1):13-25.
46. McKenzie M, Liolitsa D, Akinshina N, Campanella M, Sisodiya S, Hargreaves I, Nirmalananthan N, Sweeney MG, Abou-Sleiman PM, Wood NW, Hanna MG, Duchen MR. Mitochondrial ND5 gene variation associated with encephalomyopathy and mitochondrial ATP consumption. J Biol Chem, 2007 21;282(51):36845-52.
47. Hoyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, Bianchi K, Fehrenbacher N, Elling F, Rizzuto R, Mathiasen IS, Jaattela M. Control of macroautophagy by calcium, calmodulin dependent kinase kinases and Bcl-2. Mol. Cell. 2007 25(2):193-205).
48. Campanella M, Pinton P, Rizzuto R. Mitochondrial Ca2+ homeostasis in health and diseases. Biological Research, 2004;37(4):653-60.
49. Chami M, Prandini A, Campanella M, Pinton P, Szabadkai G, Reed JC and Rizzuto R. Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region. J Biol Chem 2004 Dec 24;279(52):54581-9.
50. Campanella M, de Jong AS, Lanke KW, Melchers WJ, Willems PH, Pinton P, Rizzuto R, van Kuppeveld FJ. (2004). The coxsackievirus 2B protein suppresses apoptotic host cell responses by manipulating intracellular Ca2+ homeostasis. J Biol Chem 2004 Apr 30;279(18):18440-50.
51. Aguiari G*, Campanella M*, Manzati E, Pinton P, Banzi M, Moretti S, Rizzuto R, del Senno L. Expression of polycystin-1 C-terminal fragment enhances the ATP-induced Ca2+ release in human kidney cells. Biochemical Biophysical Research Communication 2003 301: 657-664.* These two authors contributed equally to this work.
52. Ferrari D, Pinton P, Szabadkai G, Chami M, Campanella M, Pozzan T, Rizzuto R. Endoplasmic reticulum, Bcl-2 and Ca2+ handling in apoptosis. Cell Calcium 2002 32(5-6):413- 20.
Michelangelo is Leader of the Modules in Pricniples and Applied Pharmacology of the Bsc Bioveterinary/Biomedical Science where he delivers most of his teaching. He is also responsible for the teaching of chemotherapy in the BVetMed course and lectures on the topic at the Graduate Accelerated BVetMed course.
Michelangelo is focused in testing novel pharmacological compounds to tackle mitochondrial dysfunction associated to pathological conditions. He is regeistred Member of the General Pharmaceutical Council formed Royal Pharmaceutical Society which entitles to practice in the United Kingdom.