Frederic D Bushman

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells
    Rik Schrijvers
    Division of Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
    Retrovirology 9:84. 2012
  2. pmc A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing
    Sylvain Meylan
    School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    BMC Genomics 12:378. 2011
  3. doi request reprint Massively parallel pyrosequencing in HIV research
    Frederic D Bushman
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    AIDS 22:1411-5. 2008
  4. pmc Retroviral integration and human gene therapy
    Frederic D Bushman
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
    J Clin Invest 117:2083-6. 2007
  5. ncbi request reprint Genome-wide analysis of retroviral DNA integration
    Frederic Bushman
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104 6076, USA
    Nat Rev Microbiol 3:848-58. 2005
  6. pmc Host cell factors in HIV replication: meta-analysis of genome-wide studies
    Frederic D Bushman
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    PLoS Pathog 5:e1000437. 2009
  7. pmc Metal binding by the D,DX35E motif of human immunodeficiency virus type 1 integrase: selective rescue of Cys substitutions by Mn2+ in vitro
    Kui Gao
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, 19104 6076, USA
    J Virol 78:6715-22. 2004
  8. ncbi request reprint Regulation of catalysis by the smallpox virus topoisomerase
    Young Hwang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 281:38052-60. 2006
  9. pmc Dynamics of gene-modified progenitor cells analyzed by tracking retroviral integration sites in a human SCID-X1 gene therapy trial
    Gary P Wang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6076, USA
    Blood 115:4356-66. 2010
  10. pmc Analysis of lentiviral vector integration in HIV+ study subjects receiving autologous infusions of gene modified CD4+ T cells
    Gary P Wang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
    Mol Ther 17:844-50. 2009

Research Grants

  1. Host Cell Response to the Early Steps of Hiv Infection
    Frederic Bushman; Fiscal Year: 2003
  2. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 2005
  3. Favored Sites for HIV Integration in the Human Genome
    Frederic Bushman; Fiscal Year: 2006
  4. Chemistry of HIV-1 Integrase Function
    Frederic Bushman; Fiscal Year: 2007
  5. Favored sites for HIV cDNA integration in the human genome
    Frederic D Bushman; Fiscal Year: 2010
  6. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 1993
  7. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 2000
  8. MOLLUSCUM CONTAGIOSUM VIRUS TOPOISOMERASE
    Frederic Bushman; Fiscal Year: 2002
  9. Massively Parallel Analysis of Integration in Therapeutic Gene Transfer
    Frederic D Bushman; Fiscal Year: 2010

Detail Information

Publications92

  1. pmc HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells
    Rik Schrijvers
    Division of Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
    Retrovirology 9:84. 2012
    ..We previously identified Hepatoma-derived growth factor related protein 2 (HRP-2) as a factor mediating LEDGF/p75-independent HIV-1 replication. However, the role of HRP-2 in HIV-1 integration site selection was not addressed...
  2. pmc A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing
    Sylvain Meylan
    School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
    BMC Genomics 12:378. 2011
    ..We have recently shown that KRAB/KAP1 can mediate long-range transcriptional repression through heterochromatin spreading, but also demonstrated that this process is at times countered by endogenous influences...
  3. doi request reprint Massively parallel pyrosequencing in HIV research
    Frederic D Bushman
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    AIDS 22:1411-5. 2008
  4. pmc Retroviral integration and human gene therapy
    Frederic D Bushman
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
    J Clin Invest 117:2083-6. 2007
    ....
  5. ncbi request reprint Genome-wide analysis of retroviral DNA integration
    Frederic Bushman
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104 6076, USA
    Nat Rev Microbiol 3:848-58. 2005
    ..Here, we review retroviral DNA integration, with emphasis on recent genome-wide studies of targeting and on the status of efforts to modulate target-site selection...
  6. pmc Host cell factors in HIV replication: meta-analysis of genome-wide studies
    Frederic D Bushman
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    PLoS Pathog 5:e1000437. 2009
    ....
  7. pmc Metal binding by the D,DX35E motif of human immunodeficiency virus type 1 integrase: selective rescue of Cys substitutions by Mn2+ in vitro
    Kui Gao
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, 19104 6076, USA
    J Virol 78:6715-22. 2004
    ....
  8. ncbi request reprint Regulation of catalysis by the smallpox virus topoisomerase
    Young Hwang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 281:38052-60. 2006
    ..These findings help elucidate the amino acid side chains involved in DNA binding and catalysis and provide guidance for designing topoisomerase poisons for use as smallpox antivirals...
  9. pmc Dynamics of gene-modified progenitor cells analyzed by tracking retroviral integration sites in a human SCID-X1 gene therapy trial
    Gary P Wang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6076, USA
    Blood 115:4356-66. 2010
    ..The approaches to sequencing and bioinformatics analysis reported here should be widely useful in assessing the outcome of gene therapy trials...
  10. pmc Analysis of lentiviral vector integration in HIV+ study subjects receiving autologous infusions of gene modified CD4+ T cells
    Gary P Wang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
    Mol Ther 17:844-50. 2009
    ....
  11. pmc Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV
    Pablo Tebas
    Department of Medicine and Center for AIDS Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    Blood 121:1524-33. 2013
    ..We conclude that gene-modified T cells have the potential to decrease the fitness of HIV-1 and conditionally replicative lentiviral vectors have a promising safety profile in T cells...
  12. pmc Associating microbiome composition with environmental covariates using generalized UniFrac distances
    Jun Chen
    Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
    Bioinformatics 28:2106-13. 2012
    ..However, these two measures assign too much weight either to rare lineages or to most abundant lineages, which can lead to loss of power when the important composition change occurs in moderately abundant lineages...
  13. pmc Assessing bacterial populations in the lung by replicate analysis of samples from the upper and lower respiratory tracts
    Emily S Charlson
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 7:e42786. 2012
    ..These methods allow identification of microbes that can replicate in the lung despite the background due to oropharyngeal microbes derived from aspiration and bronchoscopic carry-over...
  14. pmc DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer
    Gary P Wang
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    Nucleic Acids Res 36:e49. 2008
    ..The methods described here should allow integration site populations from human gene therapy to be deeply characterized with spatial and temporal resolution...
  15. ncbi request reprint DNA branch nuclease activity of vaccinia A22 resolvase
    Matthew J Culyba
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
    J Biol Chem 282:34644-52. 2007
    ..Lastly, we describe possible roles for the A22 resolvase DNA-branch nuclease activity in DNA replication and repair...
  16. pmc Variola virus topoisomerase: DNA cleavage specificity and distribution of sites in Poxvirus genomes
    Nana Minkah
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6076, USA
    Virology 365:60-9. 2007
    ..These data define the full variola virus topoisomerase recognition site and provide a new window on topoisomerase function in vivo...
  17. doi request reprint Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis
    Theresa Alenghat
    1 Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA 2 Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA 3 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nature 504:153-7. 2013
    ....
  18. pmc Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant
    Emily S Charlson
    Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Am J Respir Crit Care Med 186:536-45. 2012
    ..Long-term survival after lung transplantation is limited by infectious complications and by bronchiolitis obliterans syndrome (BOS), a form of chronic rejection linked in part to microbial triggers...
  19. pmc Role of metal ions in catalysis by HIV integrase analyzed using a quantitative PCR disintegration assay
    Tracy L Diamond
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    Nucleic Acids Res 34:6116-25. 2006
    ..e. without enzyme) can catalyze formation of a low level of PCR-amplifiable product under extreme conditions, allowing us to estimate the rate enhancement due to the IN-protein scaffold as at least 60 million-fold...
  20. pmc A method to sequence and quantify DNA integration for monitoring outcome in gene therapy
    Troy Brady
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    Nucleic Acids Res 39:e72. 2011
    ....
  21. pmc HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications
    Gary P Wang
    University of Pennsylvania, School of Medicine, Department of Microbiology, Philadelphia, PA 19104 6076, USA
    Genome Res 17:1186-94. 2007
    ..The pyrosequencing and bioinformatic methods described here should be useful for investigating many aspects of retroviral DNA integration...
  22. pmc Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic
    Kay Perry
    Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Structure 18:127-37. 2010
    ..Overall, the new structural data support a common catalytic mechanism for the TopIB superfamily but indicate distinct methods for controlling duplex rotation in the small versus large enzyme subfamilies...
  23. pmc DNA bar coding and pyrosequencing to identify rare HIV drug resistance mutations
    Christian Hoffmann
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    Nucleic Acids Res 35:e91. 2007
    ....
  24. pmc Metal cofactors in the structure and activity of the fowlpox resolvase
    Matthew J Culyba
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Mol Biol 399:182-95. 2010
    ..These data show how divalent metals dictate the conformation of FPV resolvase-DNA complexes and subsequent DNA cleavage...
  25. ncbi request reprint HIV integration site selection: targeting in macrophages and the effects of different routes of viral entry
    Stephen D Barr
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, 19104 6076, USA
    Mol Ther 14:218-25. 2006
    ..Analysis of additional published integration site sequences also indicated that the route of entry did not affect integration site selection for other viral envelopes as well...
  26. pmc Quantitation of HIV DNA integration: effects of differential integration site distributions on Alu-PCR assays
    Troy Brady
    University of Pennsylvania Perelman School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, United States
    J Virol Methods 189:53-7. 2013
    ..Thus altered integration targeting, at least to the degree achieved here, is not a major concern when using the Alu-PCR assay...
  27. pmc Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria
    Matthew R Hepworth
    Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nature 498:113-7. 2013
    ..These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4(+) T cells that limit pathological adaptive immune cell responses to commensal bacteria...
  28. pmc Structure-constrained sparse canonical correlation analysis with an application to microbiome data analysis
    Jun Chen
    Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA19104, USA
    Biostatistics 14:244-58. 2013
    ..Both simulations and real data applications show that ssCCA performs better than the standard sparse CCA in identifying meaningful variables when there are structures in the data...
  29. pmc Conservation of gene cassettes among diverse viruses of the human gut
    Samuel Minot
    Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 7:e42342. 2012
    ..These findings thus connect contemporary metagenomic analysis with classical studies of bacteriophage genomic cassettes. Software is available at https://sourceforge.net/projects/optitdba/...
  30. pmc Linking long-term dietary patterns with gut microbial enterotypes
    Gary D Wu
    Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 334:105-8. 2011
    ..Thus, alternative enterotype states are associated with long-term diet...
  31. pmc DNA binding and cleavage by the fowlpox virus resolvase
    Matthew J Culyba
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 284:1190-201. 2009
    ..These findings provide a tractable poxvirus resolvase usable for the development of small molecule inhibitors...
  32. pmc HIV latency and integration site placement in five cell-based models
    Scott Sherrill-Mix
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Retrovirology 10:90. 2013
    ....
  33. pmc The human gut virome: inter-individual variation and dynamic response to diet
    Samuel Minot
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genome Res 21:1616-25. 2011
    ..Thus these data provide an overview of the composition of the human gut virome and associate virome structure with diet...
  34. pmc Integration target site selection by a resurrected human endogenous retrovirus
    Troy Brady
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 23:633-42. 2009
    ..These findings indicate that accumulation of HERVs in the human germline is a two-step process: integration targeting biases direct initial accumulation, then purifying selection leads to loss of proviruses disrupting gene function...
  35. pmc Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment
    Serena Dollive
    University of Pennsylvania School of Medicine, Department of Microbiology, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 8:e71806. 2013
    ....
  36. pmc Hypervariable loci in the human gut virome
    Samuel Minot
    Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 109:3962-6. 2012
    ....
  37. pmc Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags
    Gary D Wu
    Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6076 USA
    BMC Microbiol 10:206. 2010
    ....
  38. pmc Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences
    Rick S Mitchell
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    PLoS Biol 2:E234. 2004
    ..Thus, each of the three retroviruses studied showed unique integration site preferences, suggesting that virus-specific binding of integration complexes to chromatin features likely guides site selection...
  39. pmc Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome
    Stephen D Barr
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    J Virol 79:12035-44. 2005
    ..Further analysis indicated that ERVs in humans, mice, and rats showed similar distributions, suggesting purifying selection dictated their distributions as well...
  40. pmc Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents
    Christian Hoffmann
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    PLoS ONE 8:e66019. 2013
    ..These results confirm earlier targeted studies and provide a host of new associations to consider in modeling the effects of diet on the gut microbiome and human health. ..
  41. pmc Bulged DNA substrates for identifying poxvirus resolvase inhibitors
    Matthew Culyba
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    Nucleic Acids Res 40:e124. 2012
    ..Some 1-hydroxy-1,8-naphthyridin-2(1H)-one compounds showed anti-poxvirus activity...
  42. doi request reprint Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells
    John Scholler
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 6076, USA
    Sci Transl Med 4:132ra53. 2012
    ..Engineered T cells are a promising form of synthetic biology for long-term delivery of protein-based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases...
  43. pmc Gammaretroviral integration into nucleosomal target DNA in vivo
    Shoshannah L Roth
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    J Virol 85:7393-401. 2011
    ..Thus, we conclude that favored integration near DNase I-hypersensitive sites does not imply that integration takes place exclusively in nucleosome-free regions...
  44. ncbi request reprint Structural basis for specificity in the poxvirus topoisomerase
    Kay Perry
    University of Pennsylvania School of Medicine, Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19104, USA
    Mol Cell 23:343-54. 2006
    ..The topoisomerase-DNA complex structures also provide a three-dimensional framework that may facilitate the rational design of therapeutic agents to treat poxvirus infections...
  45. pmc Switching between raltegravir resistance pathways analyzed by deep sequencing
    Rithun Mukherjee
    Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, USA
    AIDS 25:1951-9. 2011
    ..Our objective was to analyze the pathways leading to resistance of HIV to the integrase (IN) inhibitor raltegravir (RAL)...
  46. ncbi request reprint Modulating target site selection during human immunodeficiency virus DNA integration in vitro with an engineered tethering factor
    Angela Ciuffi
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6076, USA
    Hum Gene Ther 17:960-7. 2006
    ....
  47. ncbi request reprint Retroviral DNA integration: HIV and the role of LEDGF/p75
    Angela Ciuffi
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    Trends Genet 22:388-95. 2006
    ..Understanding viral integration will help improve the safety of retrovirus-based vectors used in gene therapy...
  48. pmc Division of labor within human immunodeficiency virus integrase complexes: determinants of catalysis and target DNA capture
    Tracy L Diamond
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    J Virol 79:15376-87. 2005
    ..These data specify the ligands bound at the catalytically relevant IN monomer and allow more-specific modeling of the mechanism of inhibitors that also bind this surface of IN...
  49. pmc Rapid evolution of the human gut virome
    Samuel Minot
    Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 110:12450-5. 2013
    ..We infer that the extreme interpersonal diversity of human gut viruses derives from two sources, persistence of a small portion of the global virome within the gut of each individual and rapid evolution of some long-term virome members. ..
  50. pmc Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria
    Sesh A Sundararaman
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 110:7020-5. 2013
    ....
  51. pmc Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile
    Gregory L Peterfreund
    Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America
    PLoS ONE 7:e46966. 2012
    ..The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection...
  52. pmc Topographical continuity of bacterial populations in the healthy human respiratory tract
    Emily S Charlson
    University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
    Am J Respir Crit Care Med 184:957-63. 2011
    ..However, studies of the lung are challenging due to difficulties in working with low biomass samples...
  53. doi request reprint Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry
    Jason A Wojcechowskyj
    Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA
    Cell Host Microbe 13:613-23. 2013
    ..Mechanistic studies with SRRM2 suggest that HIV-1 modulates host cell alternative splicing machinery during entry in order to facilitate virus replication and release...
  54. doi request reprint Solution conformations of prototype foamy virus integrase and its stable synaptic complex with U5 viral DNA
    Kushol Gupta
    Department of Biochemistry and Biophysics, Perelman School of Medicine and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104 6059, USA
    Structure 20:1918-28. 2012
    ..These results provide important insights into the architecture of the retroviral intasome...
  55. pmc Dynamic regulation of HIV-1 mRNA populations analyzed by single-molecule enrichment and long-read sequencing
    Karen E Ocwieja
    Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Nucleic Acids Res 40:10345-55. 2012
    ..These findings open a new window on a little studied aspect of HIV-1 replication, suggest therapeutic opportunities and provide advanced tools for the study of alternative splicing...
  56. pmc Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency
    Matthew J Pace
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS Pathog 8:e1002818. 2012
    ..These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response...
  57. pmc Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria
    Gregory F Sonnenberg
    Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 336:1321-5. 2012
    ..Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases...
  58. pmc Cxcr2 and Cxcl5 regulate the IL-17/G-CSF axis and neutrophil homeostasis in mice
    Junjie Mei
    Division of Neonatology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 122:974-86. 2012
    ....
  59. ncbi request reprint A statistical method for comparing viral growth curves
    Gary P Wang
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    J Virol Methods 135:118-23. 2006
    ..A web-based tutorial for implementing this method is available at http://microb230.med.upenn.edu/tutorials/wangTutorial...
  60. pmc In vivo genome editing restores haemostasis in a mouse model of haemophilia
    Hojun Li
    Division of Hematology, CTRB 5000, Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nature 475:217-21. 2011
    ..Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease...
  61. pmc Role of PSIP1/LEDGF/p75 in lentiviral infectivity and integration targeting
    Heather M Marshall
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 2:e1340. 2007
    ..A cellular protein, PSIP1/LEDGF/p75, binds tightly to the lentiviral-encoded integrase protein (IN), and has been reported to be important for HIV infectivity and integration targeting...
  62. pmc HIV sequence variation associated with env antisense adoptive T-cell therapy in the hNSG mouse model
    Rithun Mukherjee
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Mol Ther 18:803-11. 2010
    ..Unexpectedly, this enrichment was only detected after the challenge with HIV-1(BaL), where the viral genome would form an imperfect duplex with envAS, and not HIV-1(NL4-3), where a perfectly matched duplex would form...
  63. pmc Distribution of lentiviral vector integration sites in mice following therapeutic gene transfer to treat β-thalassemia
    Keshet Ronen
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
    Mol Ther 19:1273-86. 2011
    ..Thus, β-Thal gene correction in mice can be achieved without expansion of cells harboring vectors integrated near genes involved in growth control...
  64. ncbi request reprint DNA cleavage by the A22R resolvase of vaccinia virus
    Matthew J Culyba
    Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    Virology 352:466-76. 2006
    ..Analysis of the reaction products revealed that A22R cleaves to leave a 3' hydroxyl at the cleaved phosphodiester bond...
  65. pmc Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases
    Craig B Wilen
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS Pathog 7:e1002020. 2011
    ..These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals...
  66. pmc HIV integration targeting: a pathway involving Transportin-3 and the nuclear pore protein RanBP2
    Karen E Ocwieja
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    PLoS Pathog 7:e1001313. 2011
    ..Thus, our data support a model in which Gag-dependent engagement of the proper transport and nuclear pore machinery mediate trafficking of HIV complexes to sites of integration...
  67. pmc The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis
    Philip McKenna
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS Pathog 4:e20. 2008
    ..This work provides comprehensive data and improved methods for studying the role of commensal microbiota in macaque models of GI diseases and provides a model for the large-scale screening of the human gut microbiome...
  68. pmc Assessing the potential for AAV vector genotoxicity in a murine model
    Hojun Li
    Department of Hematology, Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Blood 117:3311-9. 2011
    ..No integration events were identified as causing increased oncogene expression. Thus, we did not find evidence that AAV vectors cause insertional activation of oncogenes and subsequent tumor formation...
  69. pmc Gene transfer in humans using a conditionally replicating lentiviral vector
    Bruce L Levine
    Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:17372-7. 2006
    ..There is no evidence for insertional mutagenesis after 21-36 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans...
  70. pmc Hepatitis C virus transmission bottlenecks analyzed by deep sequencing
    Gary P Wang
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    J Virol 84:6218-28. 2010
    ..These findings provide the most detailed sequence-based analysis of HCV transmission bottlenecks to date. The analytical methods described here are broadly applicable to studies of viral diversity using deep sequencing...
  71. pmc Low-frequency nevirapine resistance at multiple sites may predict treatment failure in infants on nevirapine-based treatment
    Dara A Lehman
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    J Acquir Immune Defic Syndr 60:225-33. 2012
    ..It remains unclear whether specific NVP resistance mutations or combinations of mutations predict virologic failure in infants when present at low frequencies before NVP-based treatment...
  72. pmc Disordered microbial communities in the upper respiratory tract of cigarette smokers
    Emily S Charlson
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 5:e15216. 2010
    ....
  73. ncbi request reprint A role for LEDGF/p75 in targeting HIV DNA integration
    Angela Ciuffi
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104 6076, USA
    Nat Med 11:1287-9. 2005
    ..LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells...
  74. pmc HIV integration site distributions in resting and activated CD4+ T cells infected in culture
    Troy Brady
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    AIDS 23:1461-71. 2009
    ..The goal of this study was to investigate whether the location of HIV integration differs in resting versus activated T cells, a feature that could contribute to the formation of latent viral reservoirs via effects on integration targeting...
  75. pmc Structural properties of HIV integrase. Lens epithelium-derived growth factor oligomers
    Kushol Gupta
    Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine and Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19105 6059, USA
    J Biol Chem 285:20303-15. 2010
    ..These IN oligomers may be involved in stages of the viral life cycle other than integration, including assembly, budding, and early replication...
  76. ncbi request reprint Retroviral DNA integration--mechanism and consequences
    Mary K Lewinski
    Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92186, USA
    Adv Genet 55:147-81. 2005
    ..Research into the mechanisms of retroviral integration site selection has shed light on the phenomena of insertional mutagenesis and viral latency...
  77. ncbi request reprint Targeting survival: integration site selection by retroviruses and LTR-retrotransposons
    Frederic D Bushman
    Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Cell 115:135-8. 2003
    ..Despite these differences, recent data hints at a common targeting mechanism-tethering of integration complexes to proteins bound at favorable sites...
  78. ncbi request reprint Thalassiolins A-C: new marine-derived inhibitors of HIV cDNA integrase
    David C Rowley
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA
    Bioorg Med Chem 10:3619-25. 2002
    ..4 microM) and an antiviral IC50 of 30 microM. Molecular modeling studies indicate a favorable binding mode is probable at the catalytic core domain of HIV-1 integrase...
  79. pmc HTLV-1 integration into transcriptionally active genomic regions is associated with proviral expression and with HAM/TSP
    Kiran N Meekings
    Department of Immunology, Wright Fleming Institute, Imperial College London, London, United Kingdom
    PLoS Pathog 4:e1000027. 2008
    ....
  80. ncbi request reprint Inhibition of retroviral pathogenesis by RNA interference
    Wen Yuan Hu
    Infectious Disease Laboratory, La Jolla, CA 92037, USA
    Curr Biol 12:1301-11. 2002
    ..It has been widely conjectured that RNAi may also serve as an antiviral system in vertebrates...
  81. ncbi request reprint RNA interference against retroviruses
    Wen Yuan Hu
    Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Virus Res 102:59-64. 2004
    ..Here we describe the use of RNA interference (RNAi) in live chick embryos to block replication of an avian retrovirus. We also describe inhibition of ASLV and HIV replication in cell culture with RNAi...
  82. pmc Retroviral DNA integration: viral and cellular determinants of target-site selection
    Mary K Lewinski
    Infectious Disease Laboratory, The Salk Institute, La Jolla, California, USA
    PLoS Pathog 2:e60. 2006
    ....
  83. pmc Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication
    Renate König
    Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 135:49-60. 2008
    ..Taken together, the multiscale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate the early steps of HIV-1 infection...
  84. pmc Single-particle image reconstruction of a tetramer of HIV integrase bound to DNA
    Gang Ren
    The Scripps Research Institute, Department of Cell Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Mol Biol 366:286-94. 2007
    ..The asymmetry of the complex is a feature not incorporated in previous structural models and potentially provides the first view of an asymmetric reaction intermediate...
  85. pmc Human immunodeficiency virus cDNA metabolism: notable stability of two-long terminal repeat circles
    Scott L Butler
    Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Virol 76:3739-47. 2002
    ..We also used the quantitative PCR methods to analyze the effects of MG132, a proteasome inhibitor, which revealed that viral complexes containing mostly completed cDNAs are the primary substrates for proteasome-mediated degradation...
  86. ncbi request reprint Total synthesis and evaluation of lamellarin alpha 20-Sulfate analogues
    Christian P Ridley
    Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093 0212, USA
    Bioorg Med Chem 10:3285-90. 2002
    ..Lamellarin alpha 13,20-disulfate is a moderate inhibitor of both HIV-1 integrase and cancer cell lines. Lamellarin H is a more potent inhibitor of HIV-1 integrase but lacked the specificity required to be medicinally useful...
  87. pmc Short pyrosequencing reads suffice for accurate microbial community analysis
    Zongzhi Liu
    Department of Chemistry and Biochemistry, UCB 215, University of Colorado at Boulder, Boulder, CO 80309 0215, USA
    Nucleic Acids Res 35:e120. 2007
    ....
  88. ncbi request reprint Modeling HIV-1 integrase complexes based on their hydrodynamic properties
    Alexei A Podtelezhnikov
    Howard Hughes Medical Institute, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0365, USA
    Biopolymers 68:110-20. 2003
    ..Our model of the integrase tetramer bound to DNA may help to design anti-integrase inhibitors...
  89. pmc Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
    J Clin Invest 118:3132-42. 2008
    ..Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer...
  90. ncbi request reprint Roles of host cell factors in circularization of retroviral dna
    Jennifer M Kilzer
    Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Virology 314:460-7. 2003
    ..None of the cellular mutations showed a strong effect on normal integration, consistent with the idea that the cellular pathways leading to circularization are not involved in productive integration...
  91. pmc The interferon response inhibits HIV particle production by induction of TRIM22
    Stephen D Barr
    Department of Medical Microbiology and Immunology, University of Alberta, Alberta Institute for Viral Immunology, Edmonton, Alberta, Canada
    PLoS Pathog 4:e1000007. 2008
    ..Mutational analyses of TRIM22 showed that the catalytic amino acids Cys15 and Cys18 of the RING domain are required for TRIM22 antiviral activity. These data disclose a pathway by which Type 1 interferons obstruct HIV replication...
  92. pmc Selection of target sites for mobile DNA integration in the human genome
    Charles Berry
    Department of Family and Preventive Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America
    PLoS Comput Biol 2:e157. 2006
    ....

Research Grants36

  1. Host Cell Response to the Early Steps of Hiv Infection
    Frederic Bushman; Fiscal Year: 2003
    ..2. Investigate the mechanism by which interferon treatment of target cells abrogates the early steps of HIV infection. 3. Use microarray technology to investigate the host cell response to early steps of infection. ..
  2. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 2005
    ..Long term, these studies, together with data on protein structures, will provide a high-resolution picture of the organization and function of preintegration complexes. ..
  3. Favored Sites for HIV Integration in the Human Genome
    Frederic Bushman; Fiscal Year: 2006
    ..abstract_text> ..
  4. Chemistry of HIV-1 Integrase Function
    Frederic Bushman; Fiscal Year: 2007
    ..The Specific Aims are: Aim 1. Functional studies of IN-DNA complexes Aim 2. Structural analysis of IN-DNA complexes. ..
  5. Favored sites for HIV cDNA integration in the human genome
    Frederic D Bushman; Fiscal Year: 2010
    ..The integration system is a target for antiviral agents, and the proposed experiments should provide information directly useful for designing inhibitors. ..
  6. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 1993
    ..Ultimately, these studies taken together will provide a high-resolution picture of the organization and mechanism of action of the preintegration complex...
  7. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 2000
    ....
  8. MOLLUSCUM CONTAGIOSUM VIRUS TOPOISOMERASE
    Frederic Bushman; Fiscal Year: 2002
    ..In addition, poxviruses have been implicated as possible biological warfare agents; thus poxvirus topoisomerase inhibitors might be use for treating such infections. ..
  9. Massively Parallel Analysis of Integration in Therapeutic Gene Transfer
    Frederic D Bushman; Fiscal Year: 2010
    ..Here we propose to apply massively parallel pyrosequencing to analyzing vector integration in samples from the historic SCID-X1 trial. ..