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Amalio Telenti Lab
Amalio Telenti, MD-PhD, Full Professor
++41(0)21-3144097
amalio.telenti@chuv.ch
On sabbatical leave at the Ragon institute of MGH, MIT and Harvard University.
Prof Amalio Telenti is an invited lecturer at Harvard Medical School from August 2009 till July 2010. The Ragon Institute, officially established in February 2009, seeks to establish a model of scientific collaboration that links the clinical, translational and basic science expertise at MGH, MIT, Harvard and the Broad Institute to tackle the greatest global health challenges related to infectious disease research.
Research topics
Genetics of Human susceptibility to HIV infection
Humans are not equal in terms of susceptibility to infection to HIV, or in the rate of disease progression. This is evidenced by the identification of individuals that remain seronegative despite of multiple exposures to HIV-infected partners, and by the existence of the so called «long-term progressors».
Our laboratory studies the genetic variants that are associated with these differences in susceptibility. Various approaches are currently used:
- Analysis of the differences of susceptibility at the cellular level. This requires the characterization of the cellular permissiveness to HIV or HIV-derived lentiviruses. (Supported by the Swiss National Science Foundation).
- Mapping of chromosomal susceptibility loci by genome scan using linkage analysis in the in vitro setting of transduction of immortalized B cells from multigeneration families. (Supported by the Swiss National Science Foundation).
Analysis of gene candidates in a HIV-infected population. A project of the Swiss HIV Cohort Study that includes more than 6000 individuals who have provided consent for genetic analysis.
- Whole genome association study on a characterized population providing data on viral setpoint after HIV seroconversion. This is a collaborative European project supported by the Center of HIV/AIDS vaccine immunology/NIH (CHAVI).
- Evolutionary genetic assessment of proteins involved in antiretroviral defense. This includes the reconstruction of ancestral proteins, and structural analysis of protein differences among humans and non-human primates. (Supported by Interdisciplinary award of the Faculty of Biology and Medicine of Lausanne).
Pharmacogenetics of antiretroviral agents
There is considerable variation in the response to antiretroviral drugs among individuals. This concerns both the interindividual differences in pharmacokinetics, and in toxicity. Various approaches are currently used:
- Analysis of genetic variation in CYP450 and transport genes. (Supported by the Swiss National Science Foundation).
- Analysis of genetic variation in mitochondrial genes and lipid metabolism and transport genes to investigated the basis of metabolic and lipid disorders associated with use of specific antiretroviral agents. (Supported by the Swiss HIV Cohort Study).
Selected publications
2010
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1: |
Lubomirov R, di Iulio J, Fayet A, Colombo S, Martinez R, Marzolini C, Furrer H, Vernazza P, Calmy A, Cavassini M, Ledergerber B, Rentsch K, Descombes P, Buclin T, Decosterd LA, Csajka C, Telenti A; the Swiss HIV Cohort Study.
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ADME pharmacogenetics: investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformulated with ritonavir.
Pharmacogenet Genomics. 2010 Feb 4. [Epub ahead of print] |
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2: |
Rotger M, Dang KK, Fellay J, Heinzen EL, Feng S, Descombes P, Shianna KV, Ge D, Günthard HF, Goldstein DB, Telenti A; The Swiss HIV Cohort Study and the Center for HIV/AIDS Vaccine Immunology.
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Genome-Wide mRNA Expression Correlates of Viral Control in CD4+ T-Cells from HIV-1-Infected Individuals
PLoS Pathog 6(2): e1000781. doi:10.1371/journal.ppat.1000781 |
2009
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1: |
Arab-Alameddine M, Di Iulio J, Buclin T, Rotger M, Lubomirov R, Cavassini M, Fayet A, Décosterd L, Eap C, Biollaz J, Telenti A, Csajka C.
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Pharmacogenetics-Based Population Pharmacokinetic Analysis of Efavirenz in HIV-1-Infected Individuals.
Clin Pharmacol Ther. 2009 Feb 18. |
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2: |
Fellay J, Ge D, Shianna KV, Colombo S, Ledergerber B, Cirulli ET, Urban TJ, Zhang K, Gumbs CE, Smith JP, Castagna A, Cozzi-Lepri A, De Luca A, Easterbrook P, Günthard HF, Mallal S, Mussini C, Dalmau J, Martinez-Picado J, Miro JM, Obel N, Wolinsky SM, Martinson JJ, Detels R, Margolick JB, Jacobson LP, Descombes P, Antonarakis SE, Beckmann JS, O'Brien SJ, Letvin NL, McMichael AJ, Haynes BF, Carrington M, Feng S, Telenti A, Goldstein DB; NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI).
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Common genetic variation and the control of HIV-1 in humans.
PLoS Genet. 2009 Dec;5(12):e1000791. |
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3: |
Iulio JD, Fayet A, Arab-Alameddine M, Rotger M, Lubomirov R, Cavassini M, Furrer H, Günthard HF, Colombo S, Csajka C, Eap CB, Decosterd LA, Telenti A; the Swiss HIV Cohort Study.
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In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function.
Pharmacogenet Genomics. 2009 Feb 20. |
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4: |
Martin O, Valsesia A, Telenti A, Xenarios I, Stevenson BJ.
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AssociationViewer: a scalable and integrated software tool for visualization of large-scale variation data in genomic context.
Bioinformatics. 2009 Mar 1;25(5):662-3. |
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5: |
Ortiz M, Guex N, Patin E, Martin O, Xenarios I, Ciuffi A, Quintana-Murci L, and Telenti A.
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Evolutionary Trajectories of Primate Genes Involved in HIV Pathogenesis
Molecular Biology and Evolution |
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6: |
Rotger M, Bayard C, Taffé P, Martinez R, Cavassini M, Bernasconi E, Battegay M, Hirschel B, Furrer H, Witteck A, Weber R, Ledergerber B, Telenti A, and Tarr PE.
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Contribution of Genome-Wide Significant Single Nucleotide Polymorphisms and Antiretroviral Therapy to Dyslipidemia in HIV-Infected Individuals - A Longitudinal Study
Circulation: Cardiovascular Genetics. 2009 |
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7: |
Telenti A.
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HIV-1 host interactions: integration of large-scale datasets.
F1000 Biology Reports 2009, 1:71 (doi: 10.3410/B1-71) |
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8: |
Thomas R, Apps R, Qi Y, Gao X, Male V, O'hUigin C, O'Connor G, Ge D, Fellay J, Martin JN, Margolick J, Goedert JJ, Buchbinder S, Kirk GD, Martin MP, Telenti A, Deeks SG, Walker BD, Goldstein D, McVicar DW, Moffett A, Carrington M.
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HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.
Nat Genet. 2009 Dec;41(12):1290-4. |
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9: |
Urban TJ, Weintrob AC, Fellay J, Colombo S, Shianna KV, Gumbs C, Rotger M, Pelak K, Dang KK, Detels R, Martinson JJ, O'Brien SJ, Letvin NL, McMichael AJ, Haynes BF, Carrington M, Telenti A, Michael NL, Goldstein DB.
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CCL3L1 and HIV/AIDS susceptibility.
Nat Med. 2009 Oct;15(10):1110-2. |
2008
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1: |
Ge D, Zhang K, Need AC, Martin O, Fellay J, Urban TJ, Telenti A, Goldstein DB.
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WGAViewer: Software for genomic annotation of whole genome association studies.
Genome Res. 2008 Apr;18(4):640-3. |
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Goldschmidt V, Ciuffi A, Ortiz M, Brawand D, Muñoz M, Kaessmann H, Telenti A.
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Anti-Retroviral Activity of Ancestral TRIM5 (alpha)
J Virol. 2008 Mar;82(5):2089-96. |
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3: |
Kazadi K, Loeuillet C, Deutsch S, Ciuffi A, Muñoz M, Beckmann JS, Moradpour D, Antonarakis SE, Telenti A.
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Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin.
Nucleic Acids Res. 2008 Dec;36(21):6918-25. |
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4: |
Loeuillet C, Deutsch S, Ciuffi A, Robyr D, Taffé P, Muñoz M, Beckmann JS, Antonarakis SE, Telenti A.
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In Vitro Whole-Genome Analysis Identifies a Susceptibility Locus for HIV-1.
PLoS Biol. 2008 Feb 19;6(2):e32 |
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5: |
Ortiz M, Kaessmann H, Zhang K, Bashirova A, Carrington M, Quintana-Murci L, Telenti A.
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The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates.
Genes Immun. 2008 Sep;9(6):483-92. |
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6: |
Telenti A, Zanger UM.
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Pharmacogenetics of Anti-HIV Drugs.
Annu Rev Pharmacol Toxicol. 2008 Feb 10;48:227-256 |
2007
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1: |
Arnedo M, Taffé P, Sahli R, Furrer H, Hirschel B, Elzi L, Weber R, Vernazza P, Bernasconi E, Darioli R, Bergmann S, Beckmann JS, Telenti A, Tarr PE; Swiss HIV Cohort Study
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Contribution of 20 single nucleotide polymorphisms of 13 genes to dyslipidemia associated with antiretroviral therapy.
Pharmacogenet Genomics. 2007 Sep;17(9):755-64. |
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2: |
Butticaz C, Michielin O, Wyniger J, Telenti A, Rothenberger S
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Silencing of both {beta}-TrCP1 and HOS ({beta}-TrCP2) Is Required To Suppress Human Immunodeficiency Virus Type 1 Vpu-Mediated CD4 Down-Modulation.
J Virol. 2007 Feb;81(3):1502-5. |
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Fellay J, Kevin V. Shianna, Dongliang Ge, Sara Colombo, Bruno Ledergerber, Mike Weale, Kunlin Zhang, Curtis Gumbs, Antonella Castagna, Andrea Cossarizza, Alessandro Cozzi-Lepri, Andrea De Luca, Philippa Easterbrook, Patrick Francioli, Simon Mallal, Javier Martinez-Picado, José M. Miro, Niels Obel, Jason P. Smith, Josiane Wyniger, Patrick Descombes, Stylianos E. Antonarakis, Norman L. Letvin, Andrew J. McMichael, Barton F. Haynes, Amalio Telenti, David B. Goldstein
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A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1
Science. 2007 Aug 17;317(5840):944-7. |
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4: |
Loeuillet C, Weale M. Deutsch S, Rotger M. Soranzo N, Wyniger J, Lettre G, Dupré Y, Thuillard D, Beckmann JS, Antonarakis SE, Goldstein DB, Telenti A.
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Promoter polymorphisms and allelic imbalance in ABCB1 expression.
Pharmacogenet Genomics. 2007 Nov;17(11):951-9. |
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5: |
Lubomirov R, Csajka C, Telenti A.
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ADME pathway approach for pharmacogenetic studies of anti-HIV therapy.
Pharmacogenomics. 2007 Jun;8(6):623-633. |
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6: |
Martin MP, Qi Y, Gao X, Yamada E, Martin JN, Pereyra F, Colombo S, Brown EE, Shupert WL, Phair J, Goedert JJ, Buchbinder S, Kirk GD, Telenti A, Connors M, O'Brien SJ, Walker BD, Parham P, Deeks SG, McVicar DW, Carrington M.
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Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1.
Nat Genet. 2007 Jun;39(6):733-40. Epub 2007 May 13 |
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7: |
Rotger M, Saumoy M, Zhang K, Flepp M, Sahli R, Decosterd L, Telenti A; Swiss HIV Cohort Study
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Partial deletion of CYP2B6 owing to unequal crossover sith CYP2B7.
Pharmacogenet Genomics. 2007 Oct;17(10):885-90. |
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8: |
Rotger M, Tegude H, Colombo S, Cavassini M, Furrer H, Decosterd L, Blievernicht J, Saussele T, Gunthard HF, Schwab M, Eichelbaum M, Telenti A, Zanger UM
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Predictive Value of Known and Novel Alleles of CYP2B6 for Efavirenz Plasma Concentrations in HIV-infected Individuals.
Clin Pharmacol Ther. 2007 Apr;81(4):557-66. |
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9: |
Zhang KL, Mangeat B, Ortiz M, Zoete V, Trono D, Telenti A, Michielin O.
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Model Structure of Human APOBEC3G.
PLoS ONE. 2007 Apr 18;2:e378. |
2006
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1: |
Amalio Telenti and David B. Goldstein
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Genomics meets HIV.
Nat Rev Microbiol. 2006 Nov;4(11):865-73. |
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2: |
Bashirova AA, Bleiber G, Qi Y, Hutcheson H, Yamashita T, Johnson RC, Cheng J, Alter G, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, May M, Maldarelli F, Jacobson L, O'brien SJ, Telenti A, Carrington M.
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Consistent effects of TSG101 genetic variability on multiple outcomes of exposure to human immunodeficiency virus type 1.
J Virol. 2006 Jul;80(14):6757-63 |
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3: |
Goldschmidt V, Bleiber G, May M, Martinez R, Ortiz M, Telenti A; The Swiss HIV Cohort Study.
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Role of common human TRIM5alpha variants in HIV-1 disease progression.
Retrovirology. 2006 Aug 22;3:54 |
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4: |
Ortiz M, Bleiber G, Martinez R, Kaessmann H, Telenti A
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Patterns of evolution of host proteins involved in retroviral pathogenesis.
Retrovirology. 2006 Feb 7;3:11 |
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