Dr. Mary-Ellen Harper

Biography

Dr. Mary-Ellen Harper holds a Tier I Canada Research Chair in Mitochondrial Bioenergetics and Metabolic Health. 

Research Interests

Mammalian Bioenergetics: Metabolic Significance and Control of Mitochondrial Uncoupling Processes

Energy conversion processes in mammalian cells are far from perfect. The research conducted in Dr Harper's laboratory focuses specifically on the metabolic pathways that affect efficiency of energy transduction processes within different cells of the body. The cellular organelle 'charged' with the responsibility of energy conversion is the mitochondrion. It is there that the oxidation of various energy substrates converges for the production of the universal energy currency of cells, ATP. The efficiency of mitochondrial ATP synthesis, or oxidative phosphorylation, varies between different tissues of the body; between different metabolic states; and between different disease states (e.g., thyroid disorders).

The overall aim of the research projects conducted in the Harper lab is to better understand the control of cellular energy transduction processes in health and disease.

In particular, Dr. Harper's laboratory investigates the metabolic significance and control of the uncoupling of oxidation (‘fuel burning’) from ATP production and energy storage. This process is also called mitochondrial proton leak. Proton leak is controlled by the uncoupling proteins (UCPs), especially by UCP1 in brown adipose tissue, and is controlled by the adenine nucleotide translocator (ANT). UCPs and ANTs are subfamilies of the mitochondrial carrier protein family and are located in the mitochondrial inner membrane. During proton leak states, fuel is oxidized, and the energy is released (or "wasted") as heat, instead of being converted to ATP. The molecular control and functions of such seemingly wasteful processes are major interests of the lab. Some of the possible benefits of proton leak include decreased oxidative stress, and improved metabolic flexibility. Recent work also focuses on the formation of mitochondrial supercomplexes, which also affect efficiency of cellular energy transduction. The research has important implications for  metabolic diseases including obesity and diabetes, as well as cardiovascular diseases, and other diseases in which mitochondrial dysfunction is of importance.

Graduate Student and Postdoctoral Fellow Supervisions

Completed:

23 M.Sc. Shadi MONEMDJOU, 1998; Manon GAGNÉ, 1999; Andreas ANTONIOU, 2001; Darcy MacLELLAN 2007; Sean CRAWFORD, 2009; Carmen ESTEY 2009; Adrienne GOWING, 2010; Cynthia MOFFAT, 2010; Rui ZHANG, 2012; Cyril ADJEITEY, 2013, Skye McBRIDE, 2014; Lucien NADEAU, 2017(co-supervised with Dr. Céline Aguer); Awa LIAGHATI, 2017; Nina HADZIMUSTAFIC, 2020; Ziyad EL HANKOURI, 2021; Gaganvir Singh PARMAR, 2021 (best 2021 MSc thesis award); Breana HOOKS, 2022 (nominated for best MSc thesis); Mitali UPPAL (2023); Nidhi KUKSAL (2024); Ella McILROY (2024); Stephanie MYERS (2024); Charbel KARAM (2025); Michelle LEVESQUE (2026)

12 Ph.D. Shadi MONEMDJOU, 2002; Tia MOFFAT, 2007 (co-supervised with Dr.  Steffany Bennett); Lisa BEVILACQUA, 2007, Sheila COSTFORD, 2008; Brittany BEAUCHAMP, 2015; Ghadi ANTOUN, 2017 (MD-PhD; best PhD thesis award, 2017); Abi RAJKUMAR, 2018 (co-supervised with Dr. Frédérique Tesson); Georges KANAAN, 2018; Rajaa SEBAA, 2020; Michel KANAAN, 2025 (nominated for best PhD thesis); Dhanuddara MOHOTTALAGE, 2025; Claire FONG-McMASTER, 2025 (nominated for best PhD thesis)

13 PDF. Dr. Céline AGUER; Dr. Véronic BEZAIRE; Dr. Martin GERRITS; Dr. Ryan MAILLOUX; Dr. Fiona McMURRAY; Dr. Erin SEIFERT; Dr. Brianne THRUSH; Dr. Neoma BOARDMAN (visiting PDF from University of Tromso, Norway); Dr. Denis BLONDIN; Dr. David PATTEN; Dr. Jens Frey HALLING (visiting PDF from University of Copenhagen, Denmark); Dr. Chantal PILEGGI; Dr. Michel KANAAN

Current (In progress):

4 Ph.D.: Luke KENNEDY; Valeria VASILYEVA (MD-PhD, co-supervised with Dr. Michele ARDOLINO); Lauren HAMILTON; Ella McILROY 

2 MSc.: Matthew MAGDA; Farzaneh AMINI

1 HBSc: Julia DIEM HUM

1 Research Associate: Dr. Chantal PILEGGI

Technician: Jian Ying Xuan

Undergraduate Research Thesis Student Supervision:

2026-2027: Julia DIEM HUM; 2025-2026: Elena LEGRANA OKPU; 2024-2025: Lauren HAMILTON and Michelle LEVESQUE; 2023-2024:  Lillian ABEBE, Gurrose GAHLA; 2022-2023: Stephanie MYERS, Charbel KARAM; Ella McIlroy;  2020-21: Hussein ELKHATIB; 2019-20: Breana HOOKS; 2018-19: Gaganvir PARMAR; Nina HADZIMUSTAFIC; Ziyad EL HANKOURI; Baher MIGALLY 2017-18: Daniella FEBBRARO; 2016-17: Megan MacFarlane; Karan Gandhi; 2015-2016: Bianca ICHIM; Kijoo KIM; Cecile LE; 2014-15: Kris KOMM; Alyssa PEIXOTO; Jessica QUIZI; 2013-14: Olivier CHARETTE; 2012-13: Dhiya HASSAN, William CHEN, 2011-12: Melissa PASQUA, Aline PFEFFERLE; 2010-11: Naveen VENAYAK; 2009-10: Mark BASTIENELLI; Cyril ADJEITEY; Daniela GAMBAROTTA; 2008-9: Marisa ROSSI; Brittany BEAUCHAMP; 2007-8:Sean CRAWFORD, Samantha PREVOST, Benny HILL, Neha SARNA; 2006-7: Carmen ESTEY, Anastasia TOUR; 2005-6: Mitra ABAIEAN, Dimitre RANEV; 2004-5: Basil HUBBARD, Shehla CHAUDHRY; 2003-4: Matthew NIEDZWIECKI, Julie BEAULIEU; 2002-3: Nausheen SIDDIQUI, Marianne McGEE; 2001-2: Audrey NUK, Lorenne DOUCET; 2000-1: Lisa BEVILACQUA; 1999-2000: Veronic BEZAIRE; 1998-9: Andreas ANTONIOU, 1997-8: Shirin LAL; 1996-7: Manon GAGNE, 1995-6: Shadi MONEMDJOU

Current Research Funding

Canadian Institutes of Health Research (CIHR); Natural Sciences and Engineering Research Council (NSERC); Canadian Nuclear Laboratories; National Research Council of Canada; Canada Research Chairs program

Distinctions

• Tier 1 Canada Research Chair: Mitochondrial Bioenergetics and Metabolic Health 2024-2031
• Department of Biochemistry, Microbiology and Immunology Exceptional Service Award, 2026. 
• Association of Faculties of Medicine of Canada (AFMC) Scientist Award, 2026.
• Canadian Society for Molecular Biosciences (CSMB) Canadian Science Publishing Senior Investigator Award, 2026. 
• WIELD Trailblazer Award 2025: Women Inspiring and Elevating Leadership in Diabetes Trailblazers have made a critical impact on research and/or care in the fields of diabetes, obesity, and metabolism.
• Lifetime Achievement Award, Diabetes Canada; 2021
• University Research Chair in Mitochondrial Bioenergetics. 2016-2021; 2021-2024
• College of Reviewers, Canadian Institutes of Health Research (CIHR) 2014 -
• Visiting Research Scholar, Joslin Diabetes Research Center, Harvard Medical School. Boston, MA. Jan. – Dec. 2014
• Elected as the Canadian Representative on the (North American) Obesity Society Council. 2012-2015
• Elected to the Board of Governors, Canadian Obesity Network, 2012-
• Canadian Society for Nutritional Sciences Centrum Award, 2003
• Laura and Arthur Colwin Endowed Summer Research Fellowship, and HB Steinbach Fellowship in Physiology, Marine Biological Laboratory, Woods Hole, Massachusetts. 2002.
• Premier's Research Excellence Award, 2000.
• Canadian Foundation for Innovation Researcher, New Opportunities Award, 1998.
• John Charles Polanyi Prize - Physiology and Medicine. 1995.
• Research Associateship, Girton College, University of Cambridge. 1992.
• Natural Sciences and Engineering Research Council Postdoctoral Fellowship, 1991-3.

Selected Publications (twelve recent papers;  full list is available through ORCID)

(Dr. Harper has published 229 peer-reviewed papers that have been cited over 24,000 times, with and H index of 77 and an i10 index of 206.)

1. Chantal Pileggi*, Dhanuddara Mohottalage*, Luke S Kennedy*, Majid Nikpay, Lauren Hamilton*, Martin Roffe, Amer Jarrar, Nichole Kolozsvari, Dongdong Wang, Miroslava Cuperlovic-Culf, Tommy Alain, Gregory Steinberg, Ruth McPherson, Robert Dent, and Mary-Ellen Harper. (2026) Skeletal Muscle Reprogramming of Metabolic, Ribosomal and Developmental Pathways Contributes to Roux-en-Y Gastric Bypass-Induced Adaptation in Women. eBioMedicine (Lancet). 130: 106410. doi: 10.1016/j.ebiom.2026.106410
2. Chantal A. Pileggi*, Ella McIlroy*, Lauren M.K. Hamilton*, Nidhi Kuksal*, Luke S. Kennedy*, Valeria Vasilyeva*, Michel N. Kanaan*, Ziyad El Hankouri*, Yan Burelle, Miroslava Cuperlovic-Culf, and Mary-Ellen Harper (2026) Functional and metabolomic analyses of brown adipose tissue during cold-deacclimation reveal rapid adaptations in N-acetylated amino acid metabolism. iScience. 29(4):115146: 1-14. doi: 10.1016/j.isci.2026.115146
3. Luke Kennedy*, Mary-Ellen Harper** and Miroslava Cuperlovic-Culf** (2025) Computational Approaches to Enzymatic Reaction Assignment: A Review of Methods, Validations, and Future Directions.  Briefings in Bioinformatics. 26(6): 1-19. doi: 10.1093/bib/bbaf635
4. Claire Fong-McMaster, Serena M. Pulente, Luke S. Kennedy, Tyler K.T. Smith, Stephanie Myers, Michel N. Kanaan, Charbel Y. Karam, Matthew Cope, Michelle M. Levesque, Ella McIlroy, Ilka Lorenzen-Schmidt, Craig J. Goergen, Morgan D. Fullerton, Miroslava Cuperlovic-Culf, Erin E. Mulvihill**, and Mary-Ellen Harper**. (2025) Integrated bioinformatic and in vivo analysis confirms the cardioprotective role of OPA1. BMC Cardiovascular Disorders. 26(1):1-19. doi: 10.1186/s12872-025-05413-0
5. Luke Kennedy*, Jagdeep Sandhu, Mary-Ellen Harper** and Miroslava Cuperlovic-Culf** (2025). A hybrid machine learning framework for functional annotation of mitochondrial glutathione transport and metabolism proteins in cancers. BMC Bioinformatics. Accepted. Jan. 15, 2025. doi: 10.1186/s12859-025-06051-1
6. Michel Kanaan* Charbel Karam* Chantal Pileggi*, Luke Kennedy*, Miroslava Cuperlovic-Culf, and Mary-Ellen Harper (2025). Impaired xCT-mediated cystine uptake drives serine and proline metabolic reprogramming and mitochondrial fission in skeletal muscle cells. Redox Biol. 86: 1-17. doi: 10.1016/j.redox.2025.103839
7. Michel Kanaan*, Chantal Pileggi*, Charbel Karam*, Claire Fong-McMaster*, Luke Kennedy*, Miroslava Cuperlovic-Culf, and Mary-Ellen Harper. (2024) Cystine/glutamate antiporter xCT controls skeletal muscle glutathione redox, bioenergetics and regeneration.  Redox Biol. 73:103213. doi: 10.1016/j.redox.2024.103213.
8. Gaganvir Parmar*, Claire Fong-McMaster*, Chantal A Pileggi*, David A Patten*, Alexanne Cuillerier, Stephanie Myers*, Ying Wang, Siegfried Hekimi, Miroslava Cuperlovic-Culf and Mary-Ellen Harper. (2024) NDUFB4 participates in mitochondrial complex I supercomplex formation. Journal of Biological Chemistry.  300(2):105626. doi: 10.1016/j.jbc.2024.105626. * also selected for paper of the year award for the first author, former student in the Harper laboratory; MSc category.
9. Chantal Pileggi*, Hussein Elkhatib*, Corrine M Stewart, Irena Alecu, Marceline Côté, Steffany AL Bennett, Jagdeep K Sandhu, Miroslava Cuperlovic-Culf** and Mary-Ellen Harper**. (2023) The SARS-CoV-2 spike glycoprotein interacts with MAO-B and impairs mitochondrial energetics. Current Res Neurobiol. 5:100112. doi: 10.1016/j.crneur.2023.100112. 
10. Luke Kennedy*, Jagdeep K Sandhu, Mary-Ellen Harper**, and Miroslava Cuperlovic-Culf.** Mapping relationships between glutathione and SLC25 transporters in cancers using hybrid machine learning models. BioRxiv. Preprint posted Sept 21, 2023. doi: https://doi.org/10.1101/2023.09.20.558442 ** Co-Senior and Co-corresponding authors.
11. Chantal A. Pileggi*, Denis P. Blondin, Breana G. Hooks*, Gaganvir Parmar*, Irina Alecu, David A. Patten*, Alexanne Cuillerier, Conor O’Dwyer, A Brianne Thrush*, Morgan D. Fullerton, Steffany A.L. Bennett, Éric Doucet, François Haman, Miroslava Cuperlovic-Culf, Ruth McPherson, Robert R.M. Dent, and Mary-Ellen Harper. (2022) Exercise training enhances muscle mitochondrial metabolism in diet-resistant obesity. 83:104192. doi: 10.1016/j.ebiom.2022.104192.
12. Chantal A. Pileggi*, Breana G. Hooks*, Ruth McPherson, Robert R.M. Dent and Mary-Ellen Harper. (2022) Targeting skeletal muscle mitochondrial health in obesity. Clinical Science (Portland Press) 136:1081-1110.
13. Alameen Damer*, Sherif El Meniawy, Ruth McPherson, George Wells, Mary-Ellen Harper**, and Robert Dent** (2022) Association of muscle fibre type with measures of obesity: A systematic review.Obesity Reviews. 23(7):e13444.
14. Robert Dent, Ruth McPherson and Mary-Ellen Harper. (2020) Factors Affecting Weight Loss Variability in Obesity. Metabolism. 113:154388.
15. David A Patten*, Shawn McGuirk, Ujval Anilkumar, Ghadi Antoun*, Karan Gandhi*, Gaganvir Parmar*, Mohamed Ariff Iqbal, Jacob Wong, Richard B Richardson, Julie St-Pierre, Ruth S Slack, Mary-Ellen Harper. (2020) Altered mitochondrial fusion drives defensive glutathione synthesis in cells able to switch to glycolytic ATP production. BBA - Molecular Cell Research. Jan;1868(1):118854; PMID: 32926942.
16. Mary-Ellen Harper* and Mary Elizabeth Patti. (2020) Metabolic Terminology: What’s in a name? Nature Metabolism. 2(6):476-477.