I was originally a sport scientist and became interested in energy metabolism, mitochondria and oxidative stress. I then obtained my PhD on mitochondrial reactive oxygen species (ROS) production and ageing in Cambridge University under supervision of Prof. Martin Brand. Since then my research interests are in the areas of mitochondrial function in ageing and diseases, and I work both on mechanistic investigation and translational studies. Recently senescent cell targeted therapies that involve manipulation of mitochondrial function have become one of my research focuses.

My scientific contributions:

In my early career, I have characterised superoxide production by mitochondria in drosophila models, and showed membrane potential dependencies in reverse flow linked superoxide production by complex I. Then using mouse models, I have found mitochondrial complex I assembly status can predict lifespan potentials, which was linked with more coupled mitochondria and lower ROS production. I also found a non-canonical function of mTERT protein in improving mitochondrial function under dietary restriction, especially in brain.

I am also interested in critical evaluation of methodologies and have made an important discovery which explained previously unknown ‘background’ signal in Amplex Red based hydrogen peroxide detection, one of the most widely used methods for ROS measurements by biological materials. I found that carboxylesterase in mitochondrial matrix in various cell types can convert Amplex Red to resorufin in absence of oxygen, light nor any catalysts, and proposed that inhibitors for carboxylesterase such as PMSF should be included in the experiments. This has now become a necessary step for Amplex red assay.

In the area of cell senescence, I have made the original discovery that post-mitotic neurons develop senescent phenotype.  I have also shown the effects of dietary restriction in reducing senescent cells in multiples of tissues, which were linked with improved tissue conditions.

Additional work:

Ageing mouse colony and tissue bank: I have taken a leading role in conducting the experiments and managing tissue bank for wild type ageing mice colonies and life-long dietary restriction study in both males and females. We are always open for collaboration, and if you are interested in our tissue bank resources, please get in touch!

Seahorse XF Analyzer: We were one of the first research groups to start using Seahorse XF Analyzer in Europe, and from the early phase of the technology development I have worked closely with the manufacturer and the research community for methodological optimisation and scientific discussions. I have since supervised over 30 seahorse based projects for both internal and external researchers from academic institutions and industry. With increasing and overwhelming demand of Seahorse analyser usage, I have made a central role to establish  Seahorse core facility under the management of NU Flow Cytometry Core Facility, and I worked as a part time scientific officer during the first 2 years for its development . I continue acting as a consultant for Seahorse experiments.

 Qualifications:

• BSc in Human Sciences, University College London
• MSc in Sport and Exercise Sciences, University of Glasgow
• PhD in Biochemistry, Cambridge University

Memberships:

• Alliance for Healthy Ageing (Committee member)
• MIA Portugal (Scientific advisory board)  (https://twitter.com/_mia_portugal?lang=en-GB)
• CIMA (https://www.cimauk.org)
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  UK SPINE (https://www.kespine.org.uk)
• Ageing and Geroscience Theme (committee member)

Research interests - Ageing:

I have always been marvelled by how life-forms manage to survive by adjusting and maintaining physiological homeostasis amid stresses and fluctuating environments, by incredible layers of mechanisms at different levels. As a classic definition of ageing, A. Comfort wrote ‘…the power of self-adjustment and self maintenance declines with the passage of time, and the probability of disease and death increases.' (The Biology of Senescence (1956)).

Thus research on ageing is linked with understanding how we survive and uncovering why we start failing to respond to stress and lose homeostasis (‘self-adjustment and self maintenance’), and I found it fascinating.

Even at mitochondrial levels, we can see an example of a decline of ‘self-adjustment’; in senescent cells, functional capacity to maintain membrane potentials become much lower than in young cells, and it is one of the therapeutic targets for anti-ageing in my research.

Current research projects:

• Understanding the nature of mitochondrial dysfunction in senescent cells
• Novel senolytic discovery, with mitochondrial focus
• Senescent cell targeted therapies against skin ageing
• Using senolytics as adjuvant cancer therapies
• Developing in vivo imaging tool for senescent cell monitoring

Open vacancies:

No vacancies are currently available but we always welcome an interest from enthusiastic students and postdocs who are interested in applying for funding.

To discuss available options informally, please forward me your curriculum vitae and research interests.

• Lecturer on MRes in Biology of Ageing
• Project supervision for BSc and MRes courses
• PhD students supervisor
• Leading seminars and practical sessions for undergraduate students
• Hosting and supervising summer students, short term placement students from overseas, and visiting scholars
• MIA Portugal Ageing spring school organisation

• Low E, Alimohammadiha G, Smith LA, Costello LF, Przyborski SA, von Zglinicki T, Miwa S. How good is the evidence that cellular senescence causes skin ageing?. Ageing Research Reviews 2021, 71, 101456.
• Blair HR, Tomas C, Miwa S, Heath A, Russell A, Ginkel M-V, Gunn D, Walker M. Peroxisomes and pancreatic beta-cell lipo-dysfunction. Journal of Diabetes and its Complications 2021, 35(3), 107843.
• Von Zglinicki T, Wan T, Miwa S. Senescence in Post-Mitotic Cells: A Driver of Aging?. Antioxidants and Redox Signaling 2021, 34(4), 308-323.
• Braude S, Holtze S, Begall S, Brenmoehl J, Burda H, Dammann P, del Marmol D, Gorshkova E, Henning Y, Hoeflich A, Hohn A, Jung T, Hamo D, Sahm A, Shebzukhov Y, Sumbera R, Miwa S, Vyssokikh MY, von Zglinicki T, Averina O, Hildebrandt TB. Surprisingly long survival of premature conclusions about naked mole-rat biology. Biological Reviews 2021, 96(2), 376-393.
• Abdelghany TM, Leitch AC, Nevjestic I, Ibrahim I, Miwa S, Wilson C, Heutz S, Wright MC. Emerging risk from "environmentally-friendly" solvents: Interaction of methylimidazolium ionic liquids with the mitochondrial electron transport chain is a key initiation event in their mammalian toxicity. Food and Chemical Toxicology 2020, 145, 111593.
• Mavin E, Verdon B, Carrie S, Saint-Criq V, Powell J, Kuttruff CA, Ward C, Garnett JP, Miwa S. Real-time measurement of cellular bioenergetics in fully differentiated human nasal epithelial 2 cells grown at air-liquid-interface. American Journal of Physiology-Lung Cellular and Molecular Physiology 2020, 318(6), L1158-L1164.
• CorreiaMelo C, Birch J, Fielder E, Rahmatika D, Taylor J, Chapman J, Lagnado A, Carroll BM, Miwa S, Richardson G, Jurk D, Oakley F, Mann J, Mann DA, Korolchuk V, Passos JF. Rapamycin improves healthspan but not inflammaging in nfkb1-/- mice. Aging Cell 2019, 18(1), e12882.
• Short S, Fielder E, Miwa S, von Zglinicki T. Senolytics and senostatics as adjuvant tumour therapy. EBioMedicine 2019, 41, 683-692.
• Fielder E, Weigand M, Agneessens J, Griffin B, Parker C, Miwa S, von Zglinicki T. Sublethal whole-body irradiation causes progressive premature frailty in mice. Mechanisms of Ageing and Development 2019, 180, 63-69.
• da Silva PFL, Ogrodnik M, Kucheryavenko O, Glibert J, Miwa S, Cameron K, Ishaq A, Saretzki G, Nagaraja-Grellscheid S, Nelson G, von Zglinicki T. The bystander effect contributes to the accumulation of senescent cells in vivo. Aging Cell 2019, 18(1), e12848.
• Ogrodnik M, Miwa S, Tchkonia T, Tiniakos D, Wilson CL, Lahat A, Day CP, Burt A, Palmer A, Anstee QM, Nagaraja Grellscheid S, Hoeijmakers JHJ, Barnhoorn S, Mann DA, Bird TG, Vermeij WP, Kirkland JL, Passos JF, von Zglinicki T, Jurk D. Cellular senescence drives age-dependent hepatic steatosis. Nature Communications 2017, 8, 15691.
• Noble RA, Bell N, Blair H, Sikka A, Thomas H, Phillips N, Nakjang S, Miwa S, Crossland R, Rand V, Televantou D, Long A, Keun HC, Bacon CM, Bomken S, Critchlow SE, Wedge SR. Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and burkitt lymphoma. Haematologica 2017, 102(7), 1247-1257.
• Aziz SA, Wakeling LA, Miwa S, Alberdi G, Hesketh JE, Ford D. Metabolic programming of a beige adipocyte phenotype by genistein. Molecular Nutrition and Food Research 2017, 61(2), 1600574.
• Korolchuk VI, Miwa S, Carroll B, von Zglinicki T. Mitochondria in cell senescence: Is mitophagy the weakest link?. EBioMedicine 2017, 21, 7-13.
• Miwa S, Saretzki G. Telomerase and mTOR in the brain: The mitochondria connection. Neural Regeneration Research 2017, 12(3), 358-361.
• Miwa S, Treumann A, Bell A, Vistoli G, Nelson G, Hay S, von Zglinicki T. Carboxylesterase converts Amplex red to resorufin: Implications for mitochondrial H₂O₂ release assays. Free Radical Biology and Medicine 2016, 90, 173-183.
• Vistoli G, Treumann A, von Zglinicki T, Miwa S. Data from molecular dynamics simulations in support of the role of human CES1 in the hydrolysis of Amplex Red. Data in Brief 2016, 6, 865-870.
• Miwa S, Czapiewski R, Wan TF, Bell A, Hill KN, von Zglinicki T, Saretzki G. Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria. Aging 2016, 8(10), 2551-2567.
• Correia-Melo C, Marques FDM, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A, Rushton MD, Charles M, Jurk D, Tait SWG, Czapiewski R, Greaves L, Nelson G, Bohlooly-Y M, Rodriguez-Cuenca S, Vidal-Puig A, Mann D, Saretzki G, Quarato G, Green DR, Adams PD, von Zglinicki T, Korolchuk VI, Passos JF. Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO Journal 2016, 35(7), 724-742.
• Aziz SA, Wakeling LA, Miwa S, Hesketh JE, Ford D. Induction by genistein of a gene expression profile in mouse NIH3T3-L1 cells indicating conversion of white to beige adipocytes. In: Nutrition Society Scottish Section Meeting 2015, Diet, gene regulation and metabolic disease. 2015, Aberdeen, UK: Cambridge University Press.
• Dolan DWP, Zupanic A, Nelson G, Hall P, Miwa S, Kirkwood TBL, Shanley DP. Integrated Stochastic Model of DNA Damage Repair by Non-homologous End Joining and p53/p21- Mediated Early Senescence Signalling. PLoS Computational Biology 2015, 11(5), e1004246.
• Stoll EA, Makin R, Sweet IR, Trevelyan AJ, Miwa S, Horner PJ, Turnbull DM. Neural stem cells in the adult subventricular zone oxidize fatty acids to produce energy and support neurogenic activity. Stem Cells 2015, 33(7), 2306-2319.
• Spilsbury A, Miwa S, Attems J, Saretzki G. The Role of Telomerase Protein TERT in Alzheimer's Disease and in Tau-Related Pathology In Vitro. Journal of Neuroscience 2015, 35(4), 1659-1674.
• Nile DL, Brown AE, Kumaheri MA, Blair HR, Heggie A, Miwa S, Cree LM, Payne B, Chinnery PF, Brown L, Gunn DA, Walker M. Age-Related Mitochondrial DNA Depletion and the Impact on Pancreatic Beta Cell Function. PLoS One 2014, 9(12), e115433.
• Coutelle O, Hornig-Do HT, Witt A, Andree M, Schiffmann LM, Piekarek M, Brinkmann K, Seeger JM, Liwschitz M, Miwa S, Hallek M, Kronke M, Trifunovic A, Eming SA, Wiesner RJ, Hacker UT, Kashkar H. Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing. EMBO Molecular Medicine 2014, 6(5), 624-639.
• Miwa S, Jow H, Baty K, Johnson A, Czapiewski R, Saretzki G, Treumann A, von Zglinicki T. Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice. Nature Communications 2014, 5, 3837.
• Gavriilidis C, Miwa S, von Zglinicki T, Taylor RW, Young DA. Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2. Arthritis & Rheumatism 2013, 65(2), 378-387.
• Bonnen PE, Yarham JW, Besse A, Wu P, Faqeih EA, Al-Asmari AM, Saleh MAM, Eyaid W, Hadeel A, He L, Smith F, Yau S, Simcox EM, Miwa S, Donti T, Abu-Amero KK, Wong LJ, Craigen WJ, Graham BH, Scott KL, McFarland R, Taylor RW. Mutations in FBXL4 Cause Mitochondrial Encephalopathy and a Disorder of Mitochondrial DNA Maintenance. American Journal of Human Genetics 2013, 93(3), 471-481.
• Miwa S, Jow H, Treumann A, von Zglinicki T. Low abundance of the matrix arm of complex I of mice liver mitochondria predicts longevity. In: 17th European Bioenergetics Conference. 2012, Freiburg, Germany: Elsevier BV.
• Jurk D, Wang C, Miwa S, Maddick M, Korolchuk V, Tsolou A, Gonos ES, Thrasivoulou C, Saffrey JM, Cameron K, von Zglinicki T. Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell 2012, 11(6), 996-1004.
• Cameron KM, Golightly A, Miwa S, Speakman J, Boys R, von Zglinicki T. Gross energy metabolism in mice under late onset, short term caloric restriction. Mechanisms of Ageing and Development 2011, 132(4), 202-209.
• Zhang L, Rai P, Miwa S, Draman MS, Rees DA, Haridas AS, Morris DS, Tee AR, Ludgate M, Turnbull DM, Dayan CM. The Role of Mitochondria-Linked Fatty-Acid Uptake-Driven Adipogenesis in Graves Orbitopathy. Endocrinology 2021, 162(12), bqab188.