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Staff Profile

Professor Laura Greaves

Professor of Molecular Pathology

  • Telephone: +44 (0) 191 208 3074
  • Address: Mitochondrial Research Group
    Biosciences Institute,
    Â鶹´«Ã½,
    Medical School,
    Framlington Place.
    Â鶹´«Ã½ Upon Tyne.
    NE2 4HH.
Background

I am a Professor of Molecular Pathology working within the Mitochondrial Research Group within the Biosciences Institute of the Faculty of Medical Sciences My group is focussed on investigating the role of mitochondrial DNA mutations in ageing stem cells and cancer. I am interested in elucidating the mechanisms by which mitochondrial DNA mutations occur and clonally expand within individual stem cells with age, and the functional consequences of these mutations on cellular metabolism and colorectal cancer development.


I first became interested in mitochondrial genetics in 2002 when I began my PhD studies looking at the presence of mitochondrial DNA mutations in ageing human colonic epithelium. Upon discovering the high frequency of these mutations I wanted to pursue this area further to investigate their functional consequences at the cellular and tissue level, and to determine how they contribute to human ageing and disease.


Qualifications

BSc(Hons) in Pharmacology from Â鶹´«Ã½.

PhD entitled ‘Mitochondrial DNA mutations in ageing: A study in human colon’.




Research

Research Interests

  1. Investigating the link between age-related accumulation of mitochondrial dysfunction and cancer development: We have shown that there is an accumulation of mitochondrial DNA mutations in a number of tissues as we get older. These mutations cause changes in the molecular mechanisms of cellular energy metabolism and are also prevalent in human cancers. We are using model systems to induce cancer in cells with mitochondrial dysfunction to see if there is any advantage to a tumour having alterations in their metabolic pathways due to age-related mitochondrial dysfunction. We are focussing on the colon and the prostate in particular, as age is the biggest risk factor for developing cancer in these tissues. We hope to develop targeted therapies to slow cancer growth based on our findings.
  2. What is the effect of age-related mitochondrial DNA mutations on stem cell function? We know that there are changes in cellular metabolism due to age-related mitochondrial DNA mutations but we do not know what effect this has on the function of the cell as a whole, and in particular on stem cell regeneration. In this project we are testing the regenerative capacity of stem cells with mtDNA mutations and seeing whether we can modulate the regenerative response.
  3. Why are inherited mtDNA mutations lost from stem cell populations with age? In contrast to ageing cells, some stem cell populations in patients with inherited mitochondrial DNA diseases are able to selectively deplete the levels of mutated mitochondrial DNA over time. We are investigating the underlying cellular and molecular mechanisms in the hope of harnessing these mechanisms to modulate the accumulation of age-related mitochondrial DNA mutations.
  4. What are the mechanisms underlying intestinal pathogenesis in patients with mitochondrial DNA disease. We know that bowel problems are common in patients with mitochondrial DNA disease. We are investigating the effects of mitochondrial DNA mutations on intestinal motility, the gut microbiome and gut inflammation with aim of modulating these features to reduce symptoms.

 

Teaching

Faculty of Medical Sciences MRes Programme Deputy Curriculum Chair

Leading seminars and practical sessions for undergraduate students.

Lecturer on MRes in Mitochondrial Medicine 

PhD Student supervisor

BSc and MRes dissertation project supervisor

Publications

  • Articles

    • Kelly G, Kataura T, Panek J, Gailing M, Salmonowicz H, Davis A, Kendall H, Brookes C, Ayine-Tora DM, Banks P, Nelson G, Dobby L, Pitrez PR, Booth L, Costello L, Richardson GD, Lovat P, Przyborski S, Ferreira L, Greaves L, Szczepanowska K, von Zglinicki T, Miwa S, Brown M, Flagler M, Oblong JE, Bascom CC, Carroll B, Reynisson J, Korolchuk VI. . Developmental Cell 2024, 59(15), 1924-1939.e7.
    • Victorelli S, Salmonowicz H, Chapman J, Martini H, Vizioli MG, Riley JS, Cloix C, Hall-Younger E, Machado Espindola-Netto J, Jurk D, Lagnado AB, Sales Gomez L, Farr JN, Saul D, Reed R, Kelly G, Eppard M, Greaves LC, Dou Z, Pirius N, Szczepanowska K, Porritt RA, Huang H, Huang TY, Mann DA, Masuda CA, Khosla S, Dai H, Kaufmann SH, Zacharioudakis E, Gavathiotis E, LeBrasseur NK, Lei X, Sainz AG, Korolchuk VI, Adams PD, Shadel GS, Tait SWG, Passos JF. . Nature 2023, 622, 627-636.
    • Yu X, Arden C, Berlinguer-Palmini R, Chen C, Bradshaw C, Smith AL, Whitehall J, White M, Anderson S, Kattner N, Shaw J, Turnbull D, Greaves LC, Walker M. . Molecular Metabolism 2022, 60, 101489.
    • Sachdeva A, Hart CA, Carey CD, Vincent AE, Greaves LC, Heer R, Oliveira P, Brown MD, Clarke NW, Turnbull DM. . Scientific Reports 2022, 12, 6660.
    • Fuller A, Okwose N, Scragg J, Eggett C, Luke P, Bandali A, Velicki R, Greaves L, MacGowan GA, Jakovljevic DG. . Experimental Gerontology 2021, 149, 111340.
    • Stamp C, Whitehall JC, Smith ALM, Houghton D, Bradshaw C, Stoll EA, Blain AP, Turnbull DM, Greaves LC. . Aging Cell 2021, 20(3), e13321.
    • Lawless C, Greaves L, Reeve AK, Turnbull DM, Vincent AE. . Open biology 2020, 10(5), 200061.
    • Dobson PF, Dennis EP, Hipps D, Reeve A, Laude A, Bradshaw C, Stamp C, Smith A, Deehan DJ, Turnbull DM, Greaves LC. . Scientific Reports 2020, 10(1), 11643.
    • Smith ALM, Whitehall JC, Bradshaw C, Gay D, Robertson F, Blain AP, Hudson G, Pyle A, Houghton D, Hunt M, Sampson JN, Stamp C, Mallett G, Amarnath S, Leslie J, Oakley F, Wilson L, Baker A, Russell OM, Johnson R, Richardson CA, Gupta B, McCallum I, McDonald SAC, Kelly S, Mathers JC, Heer R, Taylor RW, Perkins ND, Turnbull DM, Sansom OJ, Greaves LC. . Nature Cancer 2020, 1, 976-989.
    • Anderson R, Lagnado A, Maggiorani D, Walaszczyk A, Dookun E, Chapman J, Birch J, Salmonowicz H, Ogrodnik M, Jurk D, Proctor C, Correia-Melo C, Victorelli S, Fielder E, Berlinguer-Palmini R, Owens WA, Greaves L, Kolsky K, Parini A, Douin-Echinard V, LeBrasseur N, Arthur H, Tual-Chalot S, Schafer M, Roos C, Miller J, Robertson N, Mann J, Adams P, Tchkonia T, Kirkland J, Mialet-Perez J, Richardson GD, Passos J. . The EMBO Journal 2019, 38(5), e100492.
    • Breininger SP, Malcomson FC, Afshar S, Turnbull DM, Greaves L, Mathers JC. . Proceedings of the Nutrition Society 2019, 78(3), 426-437.
    • Malcomson FC, Breininger SP, ElGendy K, Joel A, Ranathunga T, Hill TR, Bradburn DM, Turnbull DM, Greaves LC, Mathers JC. . Nutrition and Health 2019, 25(3), 231-238.
    • Paish H, Reed L, Brown H, Bryan M, Govaere O, Leslie J, Barksby B, GarciaMacia M, Watson A, Xu X, Zaki M, Greaves L, Whitehall J, French J, White S, Manas D, Robinson S, Spoletini G, Griffiths C, Mann DA, Borthwick LA, Drinnan M, Mann J, Oakley F. . Hepatology 2019, 70(4), 1377-1391.
    • Stamp C, Zupanic A, Sachdeva A, Stoll EA, Shanley DP, Mathers JC, Kirkwood TBL, Heer R, Simons BD, Turnbull DM, Greaves LC. . EBioMedicine 2018, 31, 166-173.
    • Su T, Grady JP, Afshar S, McDonald SAC, Taylor RW, Turnbull DM, Greaves LC. . The Journal of Pathology 2018, 246(4), 427-432.
    • Houghton D, Stewart CJ, Stamp C, Nelson A, Ajami NJ, Petrosino JF, Wipat A, Trenell MI, Turnbull DM, Greaves LC. . The Journals of Gerontology: Series A, Biological Sciences & Medical Sciences 2018, 73(5), 571-578.
    • Simard M-L, Mourier A, Greaves LC, Taylor RW, Stewart JB. . Journal of Pathology 2018, 245(3), 311-323.
    • Moad M, Hannezo E, Buczacki SJ, Wilson L, ElSherif A, Sims D, Pickard R, Wright NA, Williamson SC, Turnbull DM, Taylor RW, Greaves L, Robson CN, Simons BD, Heer R. . Cell Reports 2017, 20(7), 1609-1622.
    • Bury AG, Pyle A, Elson JL, Greaves L, Morris CM, Hudson G, Pienaar IS. . Annals of Neurology 2017, 82(6), 1016-1021.
    • Dobson PF, Rocha MC, Grady JP, Chrysostomou A, Hipps D, Watson S, Greaves LC, Deehan DJ, Turnbull DM. . Scientific Reports 2016, 6, 31907.
    • 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. . EMBO Journal 2016, 35(7), 724-742.
    • Tullo E, Greaves L, Wakeling L. . Educational Gerontology 2016, 42(10), 698-705.
    • 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.
    • Elson JL, Smith PM, Greaves LC, Lightowlers RN, Chrzanowska-Lightowlers ZMA, Taylor RW, Vila-Sanjurjo A. . Mitochondrion 2015, 25, 17-27.
    • Deuse T, Wang D, Stubbendorff M, Itagaki R, Grabosch A, Greaves LC, Alawi M, Grunewald A, Hu XM, Hua XQ, Velden J, Reichenspurner H, Robbins RC, Jaenisch R, Weissman IL, Schrepfer S. . Cell Stem Cell 2015, 16(1), 33-38.
    • Gorman GS, Blakely EL, Hornig-Do HT, Tuppen HAL, Greaves LC, He LP, Baker A, Falkous G, Newman J, Trenell MI, Lecky B, Petty RK, Turnbull DM, McFarland R, Taylor RW. . Clinical Science 2015, 128(12), 895-904.
    • 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.
    • Greaves LC, Nooteboom M, Elson JL, Tuppen HAL, Taylor GA, Commane DM, Arasaradnam RP, Khrapko K, Taylor RW, Kirkwood TBL, Mathers JC, Turnbull DM. . PLoS Genetics 2014, 10(9), e1004620.
    • Jurk D, Wilson C, Passos J, Oakley F, Correia-Melo C, Greaves L, Saretzki G, Fox C, Lawless C, Anderson R, Hewitt G, Pender SLF, Fullard N, Nelson G, Mann J, van de Sluis B, Mann DA, von Zglinicki T. . Nature Communications 2014, 5, 4172.
    • Di Foggia V, Zhang XY, Licastro D, Gerli MFM, Phadke R, Muntoni F, Mourikis P, Tajbakhsh S, Ellis M, Greaves LC, Taylor RW, Cossu G, Robson LG, Marino S. . Journal of Experimental Medicine 2014, 211(13), 2617-2633.
    • Smith PM, Elson JL, Greaves LC, Wortmann SB, Rodenburg RJT, Lightowlers RN, Chrzanowska-Lightowlers ZMA, Taylor RW, Vila-Sanjurjo A. . Human Molecular Genetics 2013, 23(4), 949-969.
    • Greaves LC, Elson JL, Nooteboom M, Grady JP, Taylor GA, Taylor RW, Mathers JC, Kirkwood TBL, Turnbull DM. . PLoS Genetics 2012, 8(11), e1003082.
    • Greaves LC, Barron MJ, Campbell-Shiel G, Kirkwood TBL, Turnbull DM. . Mechanisms of Ageing and Development 2011, 132(11-12), 588-591.
    • Blackwood JK, Williamson SC, Greaves LC, Wilson L, Rigas AC, Sandher R, Pickard RS, Robson CN, Turnbull DM, Taylor RW, Heer R. . Journal of Pathology 2011, 225(2), 181-188.
    • Yu Wai Man P, Lai-Cheong J, Borthwick GM, He LP, Taylor GA, Greaves LC, Taylor RW, Griffiths PG, Turnbull DM. . Investigative Ophthalmology & Visual Science 2010, 51(7), 3347-3353.
    • Greaves LC, Yu-Wai-Man P, Blakely EL, Krishnan KJ, Beadle NE, Kerin J, Barron MJ, Griffiths PG, Dickinson AJ, Turnbull DM, Taylor RW. . Investigative Ophthalmology & Visual Science 2010, 51(7), 3340-3346.
    • Greaves L, Barron M, Plusa S, Kirkwood T, Mathers J, Taylor R, Turnbull D. . Experimental Gerontology 2010, 45(7-8), 573-579.
    • Nooteboom M, Johnson R, Taylor RW, Wright NA, Lightowlers RN, Kirkwood TBL, Mathers JC, Turnbull DM, Greaves LC. . Aging Cell 2010, 9(1), 96-99.
    • Greaves LC, Beadle NE, Taylor GA, Commane D, Mathers JC, Khrapko K, Turnbull DM. . Aging Cell 2009, 8(5), 566-572.
    • Fellous TG, Islam S, Tadrous PJ, Elia G, Kocher HM, Bhattacharya S, Mears L, Turnbull DM, Taylor RW, Greaves LC, Chinnery PF, Taylor G, McDonald SAC, Wright NA, Alison MR. . Hepatology 2009, 49(5), 1655-1663.
    • Mahad DJ, Ziabreva I, Campbell G, Laulund F, Murphy JL, Reeve AK, Greaves L, Smith KJ, Turnbull DM. . Journal of Neuroscience Methods 2009, 184(2), 310-319.
    • Fellous TG, McDonald SAC, Burkert J, Humphries A, Islam S, De-Alwis NMW, Gutierrez-Gonzalez L, Tadrous PJ, Elia G, Kocher HM, Bhattacharya S, Mears L, El-Bahrawy M, Turnbull DM, Taylor RW, Greaves LC, Chinnery PF, Day CP, Wright NA, Alison MR. . Stem Cells 2009, 27(6), 1410-1420.
    • McDonald SAC, Greaves LC, Gutierrez-Gonzalez L, Rodriguez-Justo M, Deheragoda M, Leedham SJ, Taylor RW, Lee CY, Preston SL, Lovell M, Hunt T, Elia G, Oukrif D, Harrison R, Novelli MR, Mitchell I, Stoker DL, Turnbull DM, Jankowski JAZ, Wright NA. . Gastroenterology 2008, 134(2), 500-510.
    • Arasaradnam RP, Greaves LC, Commane D, Greetham H, Bradburn M, Taylor RW, Turnbull DM, Mathers JC. . Gut 2007, 56, A45-A45.
    • Krishnan KJ, Greaves LC, Reeve AK, Turnbull DM. . Biogerontology 2007, 1100, 227-240.
    • Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, Leedham SJ, Deheragoda M, Sasieni P, Novelli MR, Jankowski JAZ, Turnbull DM, Wright NA, McDonald SAC. . Proceedings of the National Academy of Sciences of the United States of America 2006, 103(3), 714-719.
    • Arasaradnam RP, Greaves LC, Commane D, Mathers JC, Taylor RW, Turnbull DM. . GUT 2006, 55(S2), A24.
    • Wilkinson SC, Maas WJM, Nielsen JB, Greaves LC, van de Sandt JJM, Williams FM. . International Archives of Occupational and Environmental Health 2006, 79(5), 405-413.
    • McDonald SAC, Preston SL, Greaves LC, Leedham SJ, Lovell MA, Jankowski JAZ, Turnbull DM, Wright NA. . Cell Cycle 2006, 5(8), 808-811.
    • Taylor RW, Barron MJ, Borthwick GM, Gospel A, Chinnery PF, Samuels DC, Taylor GA, Plusa SM, Needham SJ, Greaves LC, Kirkwood TBL, Turnbull DM. . Journal of Clinical Investigation 2003, 112(9), 1351-1360.
    • Greaves LC, Wilkinson SC, Williams FM. . Toxicology 2002, 178(1), 65-66.

  • Conference Proceedings (inc. Abstract)

    • Sachdeva A, El-Sherif A, Turnbull D, Greaves L, Heer R. . In: EAU16 – 31st Annual Congress of the European Association of Urology. 2016, Munich, Germany: Elsevier.

  • Letter

    • Greaves LC, Mathers JC, Taylor RW, Turnbull DM. . Proceedings of the National Academy of Sciences of the United States of America 2009, 106(22), E57-E57.

  • Reviews

    • Smith ALM, Whitehall JC, Greaves LC. . Molecular Oncology 2022, 16(18), 3276-3294.
    • Whitehall JC, Greaves LC. . Biogerontology 2020, 21(4), 445-459.
    • Su T, Turnbull DM, Greaves LC. . Genes 2018, 9(4), 182.
    • Baines HL, Turnbull DM, Greaves LC. . Aging Cell 2014, 13(2), 201-205.
    • Greaves LC, Reeve AK, Taylor RW, Turnbull DM. . Journal of Pathology 2012, 226(2), 274-286.
    • Greaves LC, Turnbull DM. . Biochimica et biophysica acta - General subjects 2009, 1790(10), 1015-1020.
    • Krishnan KJ, Greaves LC, Reeve AK, Turnbull D. . Nucleic Acids Research 2007, 35(22), 7399-7405.
    • Greaves LC, Taylor RW. . IUBMB Life 2006, 58(3), 143-151.