Hélène Côté

Contact Information
Department of Pathology & Laboratory Medicine
University of British Columbia
UBC Hospital
#G227, 2211 Wesbrook Mall
Vancouver, BC, Canada, V6T 2B5
Tel +1-604 822 9777+1-604 822 9777
Fax +1-604 822 7635
E-mail helene.cote@ubc.ca

Current Positions

  • Associate Professor, Pathology & Laboratory Medicine, Medicine
  • CIHR New Investigator
  • 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 statins2) Acquired mitochondrial disease-like syndromes

Publications

  1. Zanet DL, Thorne A, Singer J, Maan EJ, Sattha B, Le Campion A, Soudeyns H, Pick N, Murray M, Money DM, Côté HC; for the CIHR Emerging Team grant on 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 Jan 22.
  2. 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 Jan 13:jc20133648.
  3. Zanet DL, Saberi S, Oliveira L, Sattha B, Gadawski I, Côté HC. Blood and dried blood spot telomere length measurement by qPCR: assay considerations. PLoS One. 2013;8(2):e57787.
  4. Macdonald HM, Chu J, Nettlefold L, Maan EJ, Forbes JC, Côté H, Alimenti A; CIHR Emerging Team Grant on HIV Therapy and Aging (CARMA). Bone geometry and strength are adapted to muscle force in children and adolescents perinatally infected with HIV. J Musculoskelet Neuronal Interact. 2013 Mar;13(1):53-65.
  5. Stringer HA, Sohi GK, Maguire JA, Côté HC. Decreased skeletal muscle mitochondrial DNA in patients with statin-induced myopathy. J Neurol Sci. 2013 Feb 15;325(1-2):142-7.
  6. Hukezalie KR, Thumati NR, Côté HC, Wong JM In Vitro and Ex Vivo Inhibition of Human Telomerase by Anti-HIV Nucleoside Reverse Transcriptase Inhibitors (NRTIs) but Not by Non-NRTIs. PLoS One. 2012;7(11):e47505
  7. 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. 2012 Oct 8.
  8. Côté HC, Soudeyns H, Thorne A, Alimenti A, Lamarre V, Maan EJ, Sattha B, Singer J, Lapointe N, Money DM, Forbes J; CIHR Emerging Team in HIV therapy, aging (CARMA), Wong J, Bitnun A, Samson L, Brophy J, Burdge D, Pick N, van Schalkwyk J, Montaner J, Harris M, Janssen P. Leukocyte telomere length in HIV-infected and HIV-exposed uninfected children: shorter telomeres with uncontrolled HIV viremia. PLoS One. 2012;7(7):e39266.
  9. Imam T, Jitratkosol MH, Soudeyns H, Sattha B, Gadawski I, Maan E, Forbes JC, Alimenti A, Lapointe N, Lamarre V, Money DM, Côté HC; CIHR Emerging Team Grant on HIV Therapy and Aging: CARMA. Leukocyte telomere length in HIV-infected pregnant women treated with antiretroviral drugs during pregnancy and their uninfected infants. J Acquir Immune Defic Syndr. 2012 Aug 15;60(5):495-502.
  10. Jitratkosol MH, Sattha B, Maan E, Gadawski I, Harrigan PR, Forbes J, Alimenti A, Van Schalkwyk J, Money D, Côté HC; and the CIHR Emerging team grant on HIV therapy and aging: CARMA. Blood mitochondrial DNA mutations in HIV-infected women and their infants exposed to highly active antiretroviral therapy during pregnancy. AIDS. 2012 Jan 20. [Epub ahead of print]
  11. Jardon MA, Sattha B, Braasch K, Leung AO, Côté HC, Butler M, Gorski SM, Piret JM. Inhibition of glutamine-dependent autophagy increases t-PA production in CHO Cell fed-batch processes. Biotechnol Bioeng. 2011 Nov 28. doi: 10.1002/bit.24393. [Epub ahead of print]
  12. Côté HC, Gerschenson M, Walker UA, Miro O, Garrabou G, Hammond E, Villarroya J, Giralt M, Villarroya F, Cinque P, Garcia-Arumi E, Periz AL, Pinti M, Cossarizza A. Quality assessment of human mitochondrial DNA quantification: MITONAUTS, an international multicentre survey. Mitochondrion. 2011 May;11(3):520-7.
  13. Pfeffer G, Côté HC, Montaner JS, Li CC, Jitratkosol M, Mezei MM. Ophthalmoplegia and ptosis: mitochondrial toxicity in patients receiving HIV therapy. Neurology. 2009 Jul 7;73(1):71-2.
  14. Côté HC, Raboud J, Bitnun A, Alimenti A, Money DM, Maan E, Costei A, Gadawski I, Diong C, Read S, Shen S, Harrigan PR, Burdge DR, King SM, Forbes JC. Perinatal exposure to antiretroviral therapy is associated with increased blood mitochondrial DNA levels and decreased mitochondrial gene expression in infants. J Infect Dis. 2008 Sep 15;198(6):851-9.
  15. Matsukura M, Chu FF, Au M, Lu H, Chen J, Rietkerk S, Barrios R, Farley JD, Montaner JS, Montessori VC, Walker DC, Côté HC. Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy. AIDS. 2008 Jun 19;22(10):1226-9.
  16. Ananworanich J, Nuesch R, Côté HC, Kerr SJ, Hill A, Jupimai T, Laopraynak N, Saenawat S, Ruxrungtham K, Hirschel B. Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine–a Staccato trial substudy. J Antimicrob Chemother. 2008 Jun;61(6):1340-3.
  17. Papp E, Gadawski I, Côté HC. Longitudinal effects of thymidine analogues on mtDNA, mtRNA and multidrug resistance (MDR-1) induction in cultured cells. J Antimicrob Chemother. 2008 May;61(5):1048-52.

 

Education

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

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