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Staff Profile

Dr Jim Stewart

Senior Lecturer

Background

BACKGROUND

It has been over 35 years since the first disease alleles on the mitochondrial DNA have been described. In addition, the accumulation of mitochondrial dysfunction with age is one of the nine classic hallmarks of the ageing process. The lab focuses on the following research questions – how do the mitochondria acquire these mutations? How do they clonally expand to lead to mitochondrial deficiency in somatic cells and when transmitted through the female germline? Can we generate animal models to model aspects of human mtDNA disease? What effects do these sporadic deficient cells have on organismal health and ageing?


AFFILIATION

I am a member of the Biosciences Institute and work in the Mitochondrial and Neuromuscular Diseases research theme. I am also affiliated with the Cells, Genes, Molecules Theme.

I am also a member of .


PREVIOUS POSITIONS

Research Group Leader, Max Planck Institute for Biology of Ageing, Cologne, Germany. (Feb 2014 – Oct 2020).

Senior Postdoctoral Fellow, Max Planck Institute for Biology of Ageing, Cologne, Germany. (Mar 2009 – Jan 2014).

Postdoctoral Fellow Karolinska Institutet, Division of Metabolic Diseases Stockholm, Sweden. (Nov 2005 – Dec 2009).


EDUCATION

PhD. Department of Molecular Biology and Biochemistry, Simon Fraser University, BC, Canada (Jan 2002 – Feb 2006).

MSc. Department of Molecular Biology and Biochemistry, Simon Fraser University, BC, Canada (Sep 1997 – Feb 2002).

BSc (Hons). Biology w/ Chemistry minor. University of Waterloo, ON, CANADA (Sep 1992 – May 1997)

 

FUNDING

"LifeArc Rare Disease Cluster – TreatMito" - LifeArc & Muscular Dystrophy UK. (co-I) (2025-2029)

"Purging mutant mitochondrial DNA: from mechanisms to therapies" - UKRI - MRC. (co-I) (2022-2026).

"Towards eradicating mitochondrial DNA deletions: from mechanisms to small molecule therapies" - Champ Foundation. (co-I) (072022-072025).

: an integrated phenotyping and mouse model generation platform for mitochondrial disease and dysfunction". . (04/2022-04/2027).

PAST FUNDING

"". - The Wellcome Trust. (PI within the center) (04/2022-04/2024).

"Enhancing mitochondrial DNA fidelity to improve mammalian lifespan and healthspan" - (09/2019 - 06/2023).

 

OTHER LINKS

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Research

Animal models of mitochondrial-DNA disease - Mitochondrial diseases encompass a complex genetic landscape, affecting 1:4,300 adults. While >1140 protein gene-products within mitochondria are nuclear-encoded, mutations of the 13 protein, 22 tRNA and 2 rRNAs mitochondrial-DNA genes account for ¾ of all mitochondrial-disease patients. The diseases show a surprisingly diverse array of variable physical manifestation, age of onset and severity in patients, even for mutations within the same gene. In an effort to understand this disease complexity, and aid in pre-clinical research towards treatments for mitochondrial disorders, animal models are highly sought after. Despite advances in nuclear genome-engineering, animal mitochondrial-DNA has remained resistant to transgenic manipulation (). Our team has previously developed mouse models of mitochondrial-DNA dysfunction via random mutagenesis and screening (, ), and are among only three labs in the world who have generated these mitochondrial-DNA mouse models. Work continues on charactering the pathophysiology of these models (), . , and on pre-clinical experimental therapies for these disorders (, , , ).

Method to detect and quantify mitochondrial-DNA mutations – The mosaic, cell-to-cell variability of mitochondrial-DNA mutations due to the multi-copy nature of this genome leads to specific challenges in the study of mitochondrial-DNA mutational dysfunction. We work on and refine various sequencing methods to detect, quantify and characterize mitochondrial-DNA mutations (; ; ). We also develop methods to detect mitochondrial dysfunction in tissue samples (). We have also studied the roles of suspected Base-Excision DNA repair enzymes within the mitochondria to determine what (if any) role they have on mitochondrial mutagenesis (, ).

Mitochondria-DNA mutations to reveal functional elements – The inability to manipulate animal mitochondrial-DNA has limited reverse genetics approaches to uncover and study regulatory elements. We have developed methods to study various mitochondrial processes by the study of the behaviour of mutations after random mutagenesis in the mouse () or through the study of mtDNA mutations from cancer genomics databases ().

Germline transmission and Selection on mitochondrial-DNA mutations – We were among the first to demonstration that deleterious mitochondrial-DNA mutations transmitted through the female germline undergo rapid purifying selection. (; , ). We have continue to work in this area in an attempt to unravel the various molecular events and selective forces that affect the dynamics of mitochondrial transmission (; )

Teaching

Module Lead : MCR 8013 - Designing a Research Proposal (E-learning) (2023-present)


Lectures for;

- MMB8034 (MRes Module in Mitochondrial Medicine)

- BGM1004 (Genetics)

- BGM2058 (Evolution)

- BGM3056 (Evolution and Genomics).


Project Supervisor - CMB3000 / CMB3004 and MRes MMB8098 - Research Project Supervisor


Fellow of the Medical Sciences Graduate School

Publications

  • Articles

    • Frison M, Lockey BS, Nie Y, Golder Z, Theiaspra E, Ryall CD, Lyons C, Burr SP, Prater M, Bozhilova LV, Glynos A, Stewart JB, Jones NS, Chiaratti MR, Chinnery PF. . Science 2025, 390(6769), 156-163.
    • Bal GL, Ng KY, Berzell E, Akpinar A, Ekvik AE, Koludarova L, Naddafi S, Raths C, Van-Tempest T, VanPortfliet JJ, O'Keef S, Najumudeed AK, Nyman TA, Stewart JB, West AP, Battersby BJ. . bioRxiv 2025.
    • Barrera-Paez JD, Bacman SR, Balla T, Van Booven D, Gannamedi DP, Stewart JB, Mok B, Lui DR, Lombardi DB, Griswald AJ, Nedialkova D, Moraes CT. . Science Translational Medicine 2025, 17(783), eadr0792.
    • Marques E, Burr SP, Casey AM, Stopforth RJ, Yu CS, Turner K, Wolf DM, Dilucca M, Paup V, Choudhury SR, Tyrrell VJ, Kramer R, Kanse YM, Pednekar C, Powell CA, Stewart JB, Prudent J, Murphy MP, Minczuk M, O'Donnell V, Bryant CE, Chinnery PF, Kaser A, von Kriegsheim A, Ryan DG. . Nature Communications 2025, 16(4), 10222.
    • Landoni JC, Erkul S, Laalo T, Goffart S, Kivela R, Skube K, Jokitalo E, Nieminen A, Wickstrom S, Stewart J, Suomalainen A. . Nature Communications 2024, 15, 8066.
    • Bacman SR, Barrera-Paez JD, Pinto M, Van Booven D, Stewart JB, Griswold AJ, Moraes CT. . Molecular Therapy Nucleic Acids 2024, 35(1), 102132.
    • Glynos A, Bozhilova LV, Frison M, Burr S, Stewart JB, Chinnery PF. . Science Advances 2023, 9(43), eadi403.
    • Järvinen J, Suomi F, Stewart JB, Guala D, Valori M, Jansson L, Nieminen J, McWilliams TG, Tienari PJ. . Clinical and Experimental Immunology 2023, 214(3), 304-303.
    • Burr SP, Klimm F, Glynos A, Prater M, Sendon PM, Nash P, Powell CA, Simard M-L, Bonekamp NA, Charl J, Diaz H, Bozhilova LV, Nie Y, Zhang H, Frison M, Falkenberg M, Jones N, Minczuk M, Stewart JB, Chinnery PF. . Cell 2023, 186(6), 1212-1229.
    • Su T, Gomes TMB, Smith ALM, Whitehall JL, Blain AP, Simard ML, Scholten L, Stewart JB, Turnbull DM, Lawless C, Greaves LC. Cell division can accelerate the loss of a heteroplasmic mitochondrial DNA mutation in a mouse model of mitochondrial disease. biorXiv 2023. Submitted.
    • Saini PK, Dawitz H, Aufschnaiter A, Thomas J, Amblard A, Stewart JB, Thierry-Mieg N, Ott M, Pierrel F. . Molecular Biology of the Cell 2022, 33(14).
    • Muthye VR, Mackereth CD, Stewart JB, Lavrov DV. . DNA Repair 2022, 110, 103273.
    • Zhang H, Esposito MG, Pezet M, Aryaman J, Wei W, Klimm F, Calabrese C, Burr SP, Macabelli CH, Viscomi C, Saitou M, Chiaratti M, Stewart JB, Jones N, Chinnery PF. . Science Advances 2021, 7(50), eabi5657.
    • Zekonyte U, Bacman S, Smith J, Sharer W, Tomberlin G, Stewart JB, Jantz D, Moraes C. . Nature Communications 2021, 12, 3210.
    • Basu S, Xie X, Uhler JP, Hedberg-Oldfors C, Milenkovic D, Baris O, Kimoloi S, Matic S, Stewart JB, Larsson NG, Wiesner RJ, Oldfors A, Gustafsson CM, Falkenberg M, Larsson E. . PLoS Genetics 2020, 16(12), e1009242.
    • Filograna R, Koolmeister C, Upadhyay M, Pajak A, Clemente P, Wibom R, Simard ML, Wredenberg A, Freyer C, Stewart JB, Larsson NG. . Science Advances 2019, 5(4), eaav9824.
    • Richter U, Ng KY, Suomi F, Marttinen P, Turunen T, Jackson C, Suomalainen A, Vihinen H, Jokitalo E, Nyman TA, Isokallio MA, Stewart JB, Mancini C, Brusco A, Seneca S, Lombes A, Taylor RW, Battersby BJ. . Life Science Alliance 2019, 2(1), e201800219.
    • Bacman SR, Kauppila JHK, Pereira CV, Nissanka N, Miranda M, Pinto M, Williams SL, Larsson NG, Stewart JB, Moraes CT. . Nature Medicine 2018, 24(11), 1696-1700.
    • Matic S, Jiang M, Nicholls TJ, Uhler JP, Dirksen-Schwanenland C, Polosa PL, Simard ML, Li X, Atanassov I, Rackham O, Filipovska A, Stewart JB, Falkenberg M, Larsson NG, Milenkovic D. . Nature Communications 2018, 9(1), 1202.
    • Gammage PA, Viscomi C, Simard ML, Costa ASH, Gaude E, Powell CA, Van Haute L, McCann BJ, Zhang L, Rebar EJ, Zeviani M, Frezza C, Stewart JB, Minczuk M. . Nature Medicine 2018, 24(11), 1691-1695.
    • Kauppila JHK, Bonekamp NA, Mourier A, Isokallio MA, Just A, Kauppila TES, Stewart JB, Larsson NG. . Nucleic Acids Research 2018, 46(131), 6642-6669.
    • Simard M-L, Mourier A, Greaves LC, Taylor RW, Stewart JB. . Journal of Pathology 2018, 245(3), 311-323.
    • Jiang M, Kauppila TES, Motori E, Li X, Atanassov I, Folz-Donahue K, Bonekamp NA, Albarran-Gutierrez SA, Stewart JB, Larsson NG. . Cell Metabolism 2017, 26(2), 429-436.e4.
    • Jokinen R, Marttinen P, Stewart JB, Dear NT, Battersby BJ. . Human Molecular Genetics 2016, 25(4), 706-714.
    • Rackham O, Busch JD, Matic S, Siira SJ, Kuznetsova I, Atanassov I, Ermer JA, Shearwood AMJ, Richman TR, Stewart JB, Mourier A, Milenkovic D, Larsson NG, Filipovska A. . Cell Reports 2016, 16(7), 1874-1890.
    • Kauppila JHK, Baines HL, Bratic A, Simard ML, Freyer C, Mourier A, Stamp C, Filograna R, Larsson NG, Greaves LC, Stewart JB. . Cell Reports 2016, 16(11), 2980-2990.
    • Macao B, Uhler JP, Siibak T, Zhu X, Shi Y, Sheng W, Olsson M, Stewart JB, Gustafsson CM, Falkenberg M. . Nature Communications 2015, 6, 7303.
    • Stewart JB, Alaei-Mahabadi B, Sabarinathan R, Samuelsson T, Gorodkin J, Gustafsson CM, Larsson E. . PLoS Genetics 2015, 11(3), e1005333.
    • Bratic A, Kauppila TES, Macao B, Grönke S, Siibak T, Stewart JB, Baggio F, Dols J, Partridge L, Falkenberg M, Wredenberg A, Larsson NG. . Nature Communications 2015, 6, 8808.
    • Baines HL, Stewart JB, Stamp C, Zupanic A, Kirkwood TBL, Larsson NG, Turnbull DM, Greaves LC. . Mechanisms of Ageing and Development 2014, 139, 22-30.
    • Hagström E, Freyer C, Battersby BJ, Stewart JB, Larsson NG. . Nucleic Acids Research 2014, 42(2), 1111-1116.
    • Wang W, Scheffler K, Esbensen Y, Strand JM, Stewart JB, Bjørås M, Eide L. . PLoS ONE 2014, 9(5), e96940.
    • Terzioglu M, Ruzzenente B, Harmel J, Mourier A, Jemt E, López MD, Kukat C, Stewart JB, Wibom R, Meharg C, Habermann B, Falkenberg M, Gustafsson CM, Park CB, Larsson NG. MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation. Cell Metabolism 2013, 74(4), 618-626.
    • Ross JM, Stewart JB, Hagström E, Brené S, Mourier A, Coppotelli G, Freyer C, Lagouge M, Hoffer BJ, Olson L, Larsson NG. Germline mitochondrial DNA mutations aggravate ageing and can impair brain development. Nature 2013, 501(7476), 412-415.
    • Deceglie S, Lionetti C, Stewart JB, Habermann B, Roberti M, Cantatore P, Loguercio Polosa P. Characterization of the sea urchin mitochondrial transcription factor A reveals unusual features. Mitochondrion 2013, 14(1), 34-41.
    • Freyer C, Cree LM, Mourier A, Stewart JB, Koolmeister C, Milenkovic D, Wai T, Floros VI, Hagstrom E, Chatzidaki EE, Wiesner RJ, Samuels DC, Larsson NG, Chinnery PF. . Nature Genetics 2012, 44(11), 1282-1285.
    • Damas J, Carneiro J, Gonçalves J, Stewart JB, Samuels DC, Amorim A, Pereira F. Mitochondrial DNA deletions are associated with non-B DNA conformations. Nucleic Acids Research 2012, 40(16), 7606-7621.
    • Ruzzenente B, Metodiev MD, Wredenberg A, Bratic A, Park CB, Cámara Y, Milenkovic D, Zickerman V, Wibom R, Hultenby K, Erdjument-Bromage H, Tempst P, Brandt U, Stewart JB, Gustafsson CM, Larsson NG. LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. EMBO Journal 2012, 31(2), 443-456.
    • Wanrooij S, Miralles Fusté J, Stewart JB, Wanrooij PH, Samuelsson T, Larsson NG, Gustafsson CM, Falkenberg M. In vivo mutagenesis reveals that OriL is essential for mitochondrial DNA replication. EMBO Reports 2012, 13(12), 1130-1137.
    • Ameur A, Stewart JB, Freyer C, Hagström E, Ingman M, Larsson NG, Gyllensten U. Ultra-deep sequencing of mouse mitochondrial DNA: mutational patterns and their origins. PLoS Genetics 2011, 7(3), e1002028.
    • Bratic A, Wredenberg A, Grönke S, Stewart JB, Mourier A, Ruzzenente B, Kukat C, Wibom R, Habermann B, Partridge L, Larsson NG. The bicoid stability factor controls polyadenylation and expression of specific mitochondrial mRNAs in Drosophila melanogaster. PLoS Genetics 2011, 7(10), e1002324.
    • Beckenbach AT, Stewart JB. Insect mitochondrial genomics 3: the complete mitochondrial genome sequences of representatives from two neuropteroid orders: a dobsonfly (order Megaloptera) and a giant lacewing and an owlfly (order Neuroptera). Genome 2009, 52(1), 31-38.
    • Stewart JB, Beckenbach AT. Characterization of mature mitochondrial transcripts in Drosophila, and the implications for the tRNA punctuation model in arthropods. Gene 2009, 445(1-2), 49-57.
    • Stewart J, Freyer C, Elson J, Wredenberg A, Cansu Z, Trifunovic A, Larsson N. . PLoS Biology 2008, 6(1), e10.
    • Zhou X, Solaroli N, Bjerke M, Stewart JB, Rozell B, Johansson M, Karlsson A. Progressive loss of mitochondrial DNA in thymidine kinase 2-deficient mice. Human Molecular Genetics 2008, 17(15), 2329-2335.
    • Stewart JB, Beckenback AT. Insect mitochondrial genomics 2: The complete mitochondrial genome sequence of a giant stonefly, Pteronarcys princeps, asymmetric directional mutation bias, and conserved plecopteran A+T-region elements. Genome 2006, 49(7), 815-824.
    • Stewart JB, Beckenbach AT. Insect mitochondrial genomics: the complete mitochondrial genome sequence of the meadow spittlebug Philaenus spumarius (Hemiptera: Auchenorrhyncha: Cercopoidae). Genome 2005, 48(1), 46-54.
    • Stewart JB, Beckenbach AT. Phylogenetic and genomic analysis of the complete mitochondrial DNA sequence of the spotted asparagus beetle Crioceris duodecimpunctata. Molecular Phylogenetics and Evolution 2003, 26(3), 513-26.

  • Book Chapters

    • Isokallio MA, Stewart JB. . In: Minczuk, M; Rorbach, J, ed. Mitochondrial Gene Expression: Methods and Protocols. New York: Humana, 2021, pp.117-132.
    • McCann BJ, Cox A, Gammage PA, Stewart JB, Zernicka-Goetz M, Minczuk M. . In: Jai, L, ed. Zinc Finfer Proteins: Methods and Protocols. Springer, 2018, pp.215-228.

  • Editorial

    • Chinnery PF, Craven L, Mitalipov S, Stewart JB, Herbert M, Turnbull DM. . PLoS Genetics 2014, 10(4), e1004315.

  • Reviews

    • Bernardino Gomes TM, Vincent AE, Menger KE, Stewart JB, Nicholls TJ. . Biochemical Journal 2024, 481(11), 683-715.
    • Stewart JB, Chinnery PF. . Nature Reviews Genetics 2021, 22(2), 106–118.
    • Stewart JB. . Journal of Inherited Metabolic Disease 2021, 44(2), 325-342.
    • Stewart JB, Chinnery PF. . Nature Reviews Genetics 2015, 16(9), 530-542.
    • Kauppila JHK, Stewart JB. . Biochimica et Biophysica Acta (BBA) - Bioenergetics 2015, 1847(11), 1354-1361.
    • Stewart JB, Larsson NG. . PLoS Genetics 2014, 10(10), e1004670.
    • Stewart JB, Freyer C, Elson JL, Larsson N-G. . Nature Reviews Genetics 2008, 9(9), 657-662.
    • Simon C, Buckley TR, Frati F, Stewart JB, Beckenbach AT. Incorporating molecular evolution into phylogenetic analysis, and a new compilation of conserved polymerase chain reaction primers for animal mitochondrial DNA. Annual Review og Ecology Evolution and Systematics 2006, 37, 545-579.