Hélène Côté

Contact Information
Department of Pathology & Laboratory Medicine
University of British Columbia
UBC Hospital #G135 – 2211 Wesbrook Mall
Vancouver, BC, Canada, V6T 2B5
Tel: 1-604-822-9777
Fax: 1-604-822-7635
Email: helene.cote@ubc.ca

Current Positions

  • Professor, Pathology & Laboratory Medicine, Medicine.
  • Associate member, Women’s Health Research Institute.

Research Interests

  • My research concentrates on the mitochondrial toxicity of drugs, primarily antiretroviral drugs used in HIV therapy. The use of highly active antiretroviral therapy (HAART) (triple therapy) has significantly decreased mortality in the HIV infected population. However, HIV therapy is not a cure and treatment is life-long. As HIV infected individuals survive longer, the toxicity of the drugs and the serious side effects they cause are becoming a significant cause of morbidity and mortality, not to mention a cause of non-adherence to prescribed therapy.The drugs can cause mitochondrial DNA (mtDNA) depletion through inhibition of the mtDNA replication by the mitochondrial polymerase gamma, as well as mtDNA damage through mutation/deletion. Recently, drug-induced changes in mitochondrial gene expression have also been observed. All these can lead to mitochondrial dysfunction in various tissues and a myriad of toxicity symptoms including lipoatrophy, peripheral neuropathy, hyperlactatemia/lactic acidosis, liver failure, renal failure, pancreatitis, wasting, fatigue, some of which can be fatal.Some antiretroviral drugs can also inhibit telomerase, the enzyme complex that elongates telomeric DNA. The effect of antiretroviral drug exposure during early fetal development, childhood and adulthood on telomere length is also a topic of interest in my lab.
  • Current projects in my lab include:1) Antiretroviral mitochondrial toxicity and telomere attrition in infants born to HIV-infected mothers.2) Antiretroviral mitochondrial toxicity and telomere attrition in HIV-infected adults and children, as well as during pregnancy.These two projects study the toxicity of the drug in pregnant HIV infected women and their infants, two populations who are particularly vulnerable to drug-related toxicity. The longitudinal effect of HIV therapy on mtDNA quantity and telomere length in mother and child and the potential effect on mtDNA quality in the children are being investigated.3) Mitochondrial toxicity in HIV/hepatitis C virus co-infection antiviral therapy. The HIV/HCV coinfected population is also at higher risk of drug-related adverse events as liver damage cause by both viruses and the drugs add up. We are studying the effect of antiviral drugs on the liver mitochondria in patients undergoing HCV therapy, as well as the effect of therapy on drug metabolism by the liver.
  • Other lab interests: 1) Mitochondrial toxicity of non-HIV drugs such as statins 2) Acquired mitochondrial disease-like syndromes.

Selected Publications

  1. Carter RLR, Talbot K, Hur WS, Meixner SC, Van Der Gugten JG, Holmes DT, Côté HCF, Kastrup CJ, Smith TW, Lee AYY, Pryzdial ELG. Rivaroxaban and Apixaban Induce Clotting Factor Xa Fibrinolytic Activity. J Thromb Haemost. 2018 Sep 3. doi: 10.1111/jth.14281. [Epub ahead of print].
  2. Sharma M, Lee JYJ, Tam A, Sattha B, Mackenzie IR, Vallance H, Sirrs S, Hannah-Shmouni F, Côté HCF, Mattman A. A mitochondrial DNA D loop insertion detected almost exclusively in non-replicating tissues with maternal inheritance across three generations. Mitochondrion. 2018 Aug 13. doi: 10.1016/j.mito.2018.08.002. [Epub ahead of print].
  3. Piske M, Budd MA, Qiu AQ, Maan EJ, Sauve LJ, Forbes JC, Alimenti A, Janssen P, Côté HCF. Neurodevelopmental Outcomes and in utero Antiretroviral Exposure in HIV-Exposed Uninfected Children. (accepted for publication in AIDS, June 25, 2018 AIDS-D-18-00130R1).
  4. Slogrove AL, Becquet R, Chadwick EG, Côté HCF, Essajee S, Hazra R, Leroy V, Mahy M, Murenga M, Wambui Mwangi J, Oyiengo L, Rollins N, Penazzato M, Seage III GR, Serghides L, Vicari M, Powis KM. Surviving and thriving – Shifting the public health response to HIV-exposed uninfected children: Report of the 3rdHIV-Exposed Uninfected Child Workshop. Front Pediatr. 2018 May 30;6:157.
  5. Campbell AR, Kinvig K, , Côté HCF, Lester RT, Qiu AQ, Maan EJ, Alimenti A, Pick N, Murray MCM. Health care provider utilization and cost of an mHealth intervention in vulnerable people living with HIV in Vancouver, Canada: Prospective Study. JMIR Mhealth Uhealth. 2018 Jul 9;6(7):e152.
  6. Hsieh AYY, Budd M, Deng D, Gadawska I, Côté HCF. A Monochrome Multiplex qPCR Assay for the Measurement of mtDNA content. J Mol Diagn. 2018 Jun 21. pii: S1525-1578(17)30491-9.
  7. Kalyan S, Pick N, Mai A, Murray MCM, Kidson K, Chu J, Albert AYK, Côté HCF, Maan EJ, Goshtasebi A, Money DM, Prior JC. Premature Spinal Bone Loss in Women Living with HIV is Associated with Shorter Leukocyte Telomere Length. Int J Environ Res Public Health. 2018 May 18;15(5).
  8. Arshad O, Gadawska I, Sattha B, Côté HCF, Hsieh AYY; Canadian Institutes of Health Research Team on Cellular Aging and HIV Comorbidities in Women and Children (CARMA). Elevated Cell-Free Mitochondrial DNA in Filtered Plasma Is Associated With HIV Infection and Inflammation. J Acquir Immune Defic Syndr. 2018 May 1;78(1):111-118.
  9. Budd MA, Calli K, Samson L, Bowes J, Hsieh AYY, Forbes JC, Bitnun A, Singer J, Kakkar F, Alimenti A, Maan EJ, Lewis MES, Gentile C, Côté HCF, Brophy JC. Blood Mitochondrial DNA Content in HIV-Exposed Uninfected Children with Autism Spectrum Disorder. Viruses. 2018 Feb 11;10(2).
  10. Ajaykumar A, Soudeyns H, Kakkar F, Brophy J, Bitnun A, Alimenti A, Albert AYK, Money DM, Côté HCF; CIHR Team in Cellular Aging and HIV Comorbidities in Women and Children; CIHR Team in Cellular Aging and HIV Comorbidities in Women and Children. Leukocyte Telomere Length at Birth and During the Early Life of Children Exposed to but Uninfected With HIV After In Utero Exposure to Antiretrovirals. J Infect Dis. 2018 Feb 14;217(5):710-720.
  11. Jao J, Powis KM, Kirmse B, Yu C, Epie F, Nshom E, Abrams EJ, Sperling RS, Leroith D, Geffner ME, Kurland IJ, Côté HCF. Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon. AIDS. 2017 Nov 28;31(18):2475-2481.
  12. Gonzalez-Serna A, Ajaykumar A, Gadawski I, Muñoz-Fernández MÁ, Hayashi K, Harrigan PR, Côté HCF. Rapid Decrease in Leukocyte Telomere Length following HIV Seroconversion, but not HCV Seroconversion. J Acquir Immune Defic Syndr. 2017 Sep 1;76(1):e29-e32.
  13. Kalyan S, Patel M, Kingwell E, Côté HCF, Liu D, Prior J. Competing factors link to bone health in polycystic ovary syndrome: chronic low-grade inflammation takes a toll. 2017 Jun 13;7(1):3432.
  14. Edmonds GW, Hampson SE, Côté HC, Hill PL, Klest B.Childhood Personality, Betrayal Trauma, and Leukocyte Telomere Length in Adulthood: A Lifespan Perspective on Conscientiousness and Betrayal Traumas as Predictors of a Biomarker of Cellular Aging. Eur J Pers. 2016 Sep-Oct;30(5):426-437.
  15. Mayo NE, Brouillette MJ, Fellows LK; Positive Brain Health Now Investigators.Understanding and optimizing brain health in HIV now: protocol for a longitudinal cohort study with multiple randomized controlled trials. BMC Neurol. 2016 Jan 14;16:8.
  16. Hsieh AYY, Saberi S, Ajaykumar A, Hukezalie K, Gadawski I, Sattha B, Côté HCF. Optimization of a relative telomere length assay by monochromatic multiplex qPCR on the LightCycler 480: sources of variability and quality control considerations. J Mol Diagn. 2016 May;18(3):425-37.
  17. Sokalski KM, Chu J, Mai AY, Qiu AQ, Albert AY, Zanet DL, Côté HC, Maan EJ, Pick N, Prior JC, Money DM, Murray MC; CIHR team grant on HIV therapy and aging: CARMA. Endocrine abnormalities in HIV-infected women are associated with peak viral load – the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) Cohort. Clin Endocrinol (Oxf). 2016 Mar;84(3):452-62.
  18. Money DM, Wagner EC, Maan EJ, Chaworth-Musters T, Gadawski I, van Schalkwyk JE, Forbes JC, Burdge DR, Albert AY, Lohn Z, Côté HC; Oak Tree Clinic Research Group. Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women. PLoS One. 2015 Aug 6;10(8):e0135041.
  19. Edmonds GW, Côté HCF, Hampson SE. Childhood Conscientiousness and Leukocyte Telomere Length 40 Years Later in Adult Women – Preliminary Findings of a Prospective Association. PLoS One. 2015 Jul 28;10(7):e0134077.
  20. Schlie K, Westerback A, DeVorkin L, Hughson LR, Brandon JM, MacPherson S, Gadawski I, Townsend KN, Poon VI, Elrick MA, Côté HC, Abraham N, Wherry EJ, Mizushima N, Lum JJ. Survival of Effector CD8+ T Cells during Influenza Infection Is Dependent on Autophagy. J Immunol. 2015 May 1;194(9):4277-86.
  21. Sharma AA, Jen R, Kan B, Sharma A, Marchant E, Tang A, Gadawski I, Senger C, Skoll A, Turvey SE, Sly LM, Côté HC, Lavoie PM.Impaired NLRP3 inflammasome activity during fetal development regulates IL-1β production in human monocytes. Eur J Immunol 2015 Jan;45(1):238-49.
  22. Srinivasa S, Fitch KV, Petrow E, Burdo TH, Williams KC, Lo J, Côté HCF, Grinspoon SK. Soluble CD163 is associated with shortened telomere length in HIV-infected patients. J Acquir Immune Defic Syndr 2014 Dec 1;67(4):414-8.
  23. Ngoma MS, Hunter JA, Harper JA, Church PT, Mumba S, Chandwe M, Côté HCF, Albert AY, Smith ML, Selemani C, Sandstrom PA, Bandenduck L, Ndlovu U, Khan S, Roa L, Silverman MS. Cognitive and language outcomes in HIV-uninfected infants exposed to combined antiretroviral therapy in utero and through extended breast-feeding. AIDS. 2014 Jul;28 Suppl 3:S323-30.
  24. Giesbrecht CJ, Thornton AE, Hall-Patch C, Maan EJ, Côté HCF, Money DM, Murray M, Pick N, and the CIHR team in HIV therapy and Aging. Select neurocognitive impairment in HIV-infected women: Associations with HIV plasma viral load, hepatitis C virus, and depression, but not leukocyte telomere length. PLoS One2014 Mar; 9(3):e89556.
  25. *Zanet DL, Thorne A, Singer J, Maan E, Sattha A Le Campion, Soudeyns H, B, Pick N, Murray M, Money DM, Côté HCF for the CIHR Emerging Team in HIV Therapy and Aging: CARMA. Association between short leukocyte telomere length and HIV infection in a cohort study: No evidence of a relationship with antiretroviral therapy. Clin Infect Dis. 2014 May;58(9):1322-32.
  26. Kalyan S, Huebbe P, Esatbeyoglu T, Niklowitz P, Côté HC, Rimbach G, Kabelitz D. Nitrogen-bisphosphonate therapy is linked to compromised coenzyme Q10 and vitamin E status in postmenopausal women. J Clin Endocrinol Metab. 2014 Apr;99(4):1307-13.
  27. Zanet, D, Saberi S, Oliveira L, Sattha B, Gadawski I, Côté HCF. Blood and dried blood spot telomere length measurement by qPCR: assay considerations. PLoS ONE 2013;8(2):e57787.
  28. MacDonald HM, Chu J, Nettlefold L, Maan EJ, Forbes JC, Côté HCF, Alimenti A, and the CIHR Emerging Team Grant on HIV Therapy and Aging (CARMA). Bone geometry and strength are adapted to muscle force in perinatally HIV-infected children and adolescents. J Musculoskelet Neuronal Interact. 2013 Mar;13(1):53-65.
  29. Stringer HAJ, Sohi GK, Maguire JA, Côté HCF. Decreased Skeletal Muscle Mitochondrial DNA in Patients with Statin–Induced Myopathy. J Neurol Sci. 2013 Feb 15;325(1-2):142-7.
  30. Wagner TA, Lin CH, Tobin NH, Côté HC, Sloan DD, Jerome KR, Frenkel LM. Quantification of mitochondrial toxicity in HIV-infected individuals by quantitative PCR compared to flow cytometry. Cytometry B Clin Cytom. 2013 Jan;84(1):55-8.

Education

  • Postdoctoral, University of Washington, 1998.
  • Postdoctoral, University of British Columbia, 1994.
  • Ph.D., University of British Columbia, 1993.
  • B.Sc., Laval University, 1987.