Carrie Dykes
| Title | Assistant Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Medicine |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 689
Rochester NY 14642
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Our research group is interested in several projects related to HIV-1 pathogenesis and treatment. We study the effect of anti-retroviral drug resistance mutations on HIV-1 replication capacity and resistance. We are interested in determining whether HIV-1 replication capacity as measured in cell culture is clinically related to HIV-1 pathogenesis. We have experience working with HIV-1 in cell culture and have developed several unique cell culture based assays to study HIV-1 recombination, resistance and fitness. We also have biochemistry expertise, studying the polymerization and RNase H activities of HIV-1 reverse transcriptase. We have recently shown that some drug resistant mutants grow better in the presence of the inhibitor compared to its absence. Future work will explore possible mechanisms for how this stimulation by drug occurs with the goal to develop more potent drugs for treatment. We have also shown that protease inhibitor drug resistant mutants give discordant fitness when measured in multiple-cycle versus single-cycle fitness assays, indicating that these assays measure different steps of the virus life-cycle. Future work will explore the reasons for this discrepancy using novel technologies such as nanospectroscopy and Amnis Imagestream flow cytometry. The goal is to determine whether fitness as measured in cell culture can correlate with progression to AIDS in patients.
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Block O, Mitra A, Novotny L, Dykes C. A rapid label-free method for quantitation of human immunodeficiency virus type-1 particles by nanospectroscopy. J Virol Methods. 2012 Jun; 182(1-2):70-5.
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Wang J, Zhang G, Bambara RA, Li D, Liang H, Wu H, Smith HM, Lowe NR, Demeter LM, Dykes C. Nonnucleoside reverse transcriptase inhibitor-resistant HIV is stimulated by efavirenz during early stages of infection. J Virol. 2011 Oct; 85(20):10861-73.
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Piekna-Przybylska D, Dykes C, Demeter LM, Bambara RA. Sequences in the U3 region of human immunodeficiency virus 1 improve efficiency of minus strand transfer in infected cells. Virology. 2011 Feb 20; 410(2):368-74.
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Dykes C, Wu H, Sims M, Holden-Wiltse J, Demeter LM. Human immunodeficiency virus type 1 protease inhibitor drug-resistant mutants give discordant results when compared in single-cycle and multiple-cycle fitness assays. J Clin Microbiol. 2010 Nov; 48(11):4035-43.
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Dykes C, Mukherjee AL, Bosch RJ, Connick E, Volberding PA, Demeter LM. Prevalence of primary resistance at baseline in acutely and recently infected subjects enrolled in AIDS clinical trials group protocol 371. J Acquir Immune Defic Syndr. 2010 Sep; 55(1):132-4.
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DiFrancesco R, Rosenkranz S, Mukherjee AL, Demeter LM, Jiang H, DiCenzo R, Dykes C, Rinehart A, Albrecht M, Morse GD. Quality assessment for therapeutic drug monitoring in AIDS Clinical Trials Group (ACTG 5146): a multicenter clinical trial. Ther Drug Monit. 2010 Aug; 32(4):458-66.
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Wang J, Bambara RA, Demeter LM, Dykes C. Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions. J Virol. 2010 Sep; 84(18):9377-89.
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Ma J, Dykes C, Wu T, Huang Y, Demeter L, Wu H. vFitness: a web-based computing tool for improving estimation of in vitro HIV-1 fitness experiments. BMC Bioinformatics. 2010; 11:261.
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Wang J, Liang H, Bacheler L, Wu H, Deriziotis K, Demeter LM, Dykes C. The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations. Virology. 2010 Jul 5; 402(2):228-37.
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Mitra A, Deutsch B, Ignatovich F, Dykes C, Novotny L. Nano-optofluidic detection of single viruses and nanoparticles. ACS Nano. 2010 Mar 23; 4(3):1305-12.
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Gandhi RT, Bosch RJ, Aga E, Albrecht M, Demeter LM, Dykes C, Bastow B, Para M, Lai J, Siliciano RF, Siliciano JD, Eron JJ. No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy. J Infect Dis. 2010 Jan 15; 201(2):293-6.
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Demeter LM, Jiang H, Mukherjee AL, Morse GD, DiFrancesco R, DiCenzo R, Dykes C, Sista P, Bacheler L, Klingman K, Rinehart A, Albrecht M. A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients. AIDS. 2009 Jan 28; 23(3):357-68.
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Miao H, Dykes C, Demeter LM, Cavenaugh J, Park SY, Perelson AS, Wu H. Modeling and estimation of kinetic parameters and replicative fitness of HIV-1 from flow-cytometry-based growth competition experiments. Bull Math Biol. 2008 Aug; 70(6):1749-71.
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Miao H, Dykes C, Demeter LM, Wu H. Differential equation modeling of HIV viral fitness experiments: model identification, model selection, and multimodel inference. Biometrics. 2009 Mar; 65(1):292-300.
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Dykes C, Demeter LM. Clinical significance of human immunodeficiency virus type 1 replication fitness. Clin Microbiol Rev. 2007 Oct; 20(4):550-78.
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Koval CE, Dykes C, Wang J, Demeter LM. Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. Virology. 2006 Sep 15; 353(1):184-92.
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Dykes C, Wang J, Jin X, Planelles V, An DS, Tallo A, Huang Y, Wu H, Demeter LM. Evaluation of a multiple-cycle, recombinant virus, growth competition assay that uses flow cytometry to measure replication efficiency of human immunodeficiency virus type 1 in cell culture. J Clin Microbiol. 2006 Jun; 44(6):1930-43.
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Wu H, Huang Y, Dykes C, Liu D, Ma J, Perelson AS, Demeter LM. Modeling and estimation of replication fitness of human immunodeficiency virus type 1 in vitro experiments by using a growth competition assay. J Virol. 2006 Mar; 80(5):2380-9.
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Wang J, Dykes C, Domaoal RA, Koval CE, Bambara RA, Demeter LM. The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. Virology. 2006 May 10; 348(2):462-74.
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Dykes C, Balakrishnan M, Planelles V, Zhu Y, Bambara RA, Demeter LM. Identification of a preferred region for recombination and mutation in HIV-1 gag. Virology. 2004 Sep 1; 326(2):262-79.
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Dykes C, Najjar J, Bosch RJ, Wantman M, Furtado M, Hart S, Hammer SM, Demeter LM. Detection of drug-resistant minority variants of HIV-1 during virologic failure of indinavir, lamivudine, and zidovudine. J Infect Dis. 2004 Mar 15; 189(6):1091-6.
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Dykes C, Fox K, Lloyd A, Chiulli M, Morse E, Demeter LM. Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. Virology. 2001 Jul 5; 285(2):193-203.
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Archer RH, Dykes C, Gerondelis P, Lloyd A, Fay P, Reichman RC, Bambara RA, Demeter LM. Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture. J Virol. 2000 Sep; 74(18):8390-401.
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Dykes C, Mootsikapun P, Dexter A, Berrios L, Chiulli M, Reichman RC, Demeter LM. Analysis of env sequence evolution in human immunodeficiency virus-infected patients receiving therapy with nonnucleoside reverse-transcriptase inhibitors. J Infect Dis. 2000 Jul; 182(1):316-20.
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Dykes C, Chan H, Krenitsky DM, Dewhurst S. Stringent structural and sequence requirements of the human herpesvirus 6B lytic-phase origin of DNA replication. J Gen Virol. 1997 May; 78 ( Pt 5):1125-9.
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van Loon N, Dykes C, Deng H, Dominguez G, Nicholas J, Dewhurst S. Identification and analysis of a lytic-phase origin of DNA replication in human herpesvirus 7. J Virol. 1997 Apr; 71(4):3279-84.
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Dewhurst S, Krenitsky DM, Dykes C. Human herpesvirus 6B origin: sequence diversity, requirement for two binding sites for origin-binding protein, and enhanced replication from origin multimers. J Virol. 1994 Oct; 68(10):6799-803.
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