Research Topics
| HAIG KAZAZIANSummaryAffiliation: University of Pennsylvania Country: USA Publications
Research Grants
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Detail Information
Publications
Many LINE1 elements contribute to the transcriptome of human somatic cellsSanjida H Rangwala
Department of Genetics, University of Pennsylvania School of Medicine, Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
Genome Biol 10:R100. 2009..We also examined expression of a select number of elements in different individuals...- Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscleRandy J Chandler
Genetic Diseases Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
BMC Med Genet 8:64. 2007..Current treatment regimens rely on dietary management and, in severely affected patients, liver or combined liver-kidney transplantation. For undetermined reasons, transplantation does not correct the biochemical phenotype... 
Mobile elements: drivers of genome evolutionHaig H Kazazian
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Science 303:1626-32. 2004..Although the host can often control their numbers, massive expansions of retrotransposons have been tolerated during evolution. Now mobile elements are becoming useful tools for learning more about genome evolution and gene function...- The impact of L1 retrotransposons on the human genomeH H Kazazian
Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA
Nat Genet 19:19-24. 1998..We review the impact of retrotransposons and how new insight is likely to lead to important practical applications for these intriguing mobile elements... - LINE drive. retrotransposition and genome instabilityHaig H Kazazian
Department of Genetics, School of Medicine, 475 Clinical Research Building, 415 Curie Boulevard, University of Pennsylvania, Philadelphia 19105, USA
Cell 110:277-80. 2002..If these events occur at a similar frequency in vivo, they have had a substantial effect on human genome evolution... - Genetics. L1 retrotransposons shape the mammalian genomeH H Kazazian
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Science 289:1152-3. 2000..And just how do they do this?...zip to page 1152 to find out... - Mobile elements and diseaseH H Kazazian
Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA
Curr Opin Genet Dev 8:343-50. 1998..The mechanism by which they retrotranspose and in turn aide the retrotransposition of non-autonomous elements is being elucidated... - Long-term efficacy of adeno-associated virus serotypes 8 and 9 in hemophilia a dogs and miceRita Sarkar
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104-6145, USA
Hum Gene Ther 17:427-39. 2006..Even so, translation of these robust vectors either in appropriate large animals or human beings remains challenging... - A mouse model of human L1 retrotranspositionEric M Ostertag
Department of Genetics and University of Pennsylvania School of Medicine, 475 Clinical Research Bldg, 415 Curie Blvd, Philadelphia, Pennsylvania 19104, USA
Nat Genet 32:655-60. 2002..In addition to providing a valuable in vivo model of retrotransposition in mammals, these mice are an important step in the development of a new random mutagenesis system... - Exon-trapping mediated by the human retrotransposon SVADustin C Hancks
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Genome Res 19:1983-91. 2009.... - More active human L1 retrotransposons produce longer insertionsAlexander H Farley
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Nucleic Acids Res 32:502-10. 2004..We suggest that the region containing residues 1220 and 1259 may be important in the binding of ORF2p to L1 RNA to facilitate reverse transcription... - LINE-1 ORF1 protein localizes in stress granules with other RNA-binding proteins, including components of RNA interference RNA-induced silencing complexJohn L Goodier
Dept of Genetics, University of Pennsylvania School of Medicine, Rm 515 CRB, 415 Curie Blvd, Philadelphia, PA 19104, USA
Mol Cell Biol 27:6469-83. 2007..We suggest that targeting ORF1p, and possibly the L1 RNP, to stress granules is a mechanism for controlling retrotransposition and its associated genetic and cellular damage... - A potential role for the nucleolus in L1 retrotranspositionJohn L Goodier
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
Hum Mol Genet 13:1041-8. 2004..These findings help explain the presence of chimeras between L1s and small RNA gene sequences recently discovered in the human genome... - Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotypeRita Sarkar
Department of Genetics, University of Pennsylvania 415 Curie Blvd, CRB Rm 475, Philadelphia, PA 19104, USA
Blood 103:1253-60. 2004..We also evaluated AAV8 against AAV2 in intraportal and tail vein injections. AAV8 gave 100% correction of plasma FVIII activity irrespective of the vector type or route of administration... - An important role for RUNX3 in human L1 transcription and retrotranspositionNuo Yang
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Nucleic Acids Res 31:4929-40. 2003.... 
Retrotransposons revisited: the restraint and rehabilitation of parasitesJohn L Goodier
Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA
Cell 135:23-35. 2008..Recent insights and new technologies promise answers to fundamental questions about the biology of transposable elements...- Discrete subcellular partitioning of human retrotransposon RNAs despite a common mechanism of genome insertionJohn L Goodier
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Hum Mol Genet 19:1712-25. 2010..Such variability predicts significant differences in the life cycles of these elements... - Tracking an embryonic L1 retrotransposition eventEline T Luning Prak
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 405B Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 100:1832-7. 2003..The retrotransposition event characterized here has occurred at a very early stage in the development of an L1-EGFP transgenic founder mouse... - A novel testis ubiquitin-binding protein gene arose by exon shuffling in hominoidsDaria V Babushok
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
Genome Res 17:1129-38. 2007..PIPSL is a tightly regulated, testis-specific novel ubiquitin-binding protein formed by an unusual exon-shuffling mechanism in hominoid primates and represents a key example of rapid evolution of a testis-specific gene... - High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomesAdam D Ewing
University of Pennsylvania Department of Genetics, Philadelphia, Pennsylvania 19104, USA
Genome Res 20:1262-70. 2010..05 is between 3000 and 10,000... - L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicismHiroki Kano
Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA
Genes Dev 23:1303-12. 2009..Thus, L1 creates somatic mosaicism during mammalian development, suggesting a role for L1 in carcinogenesis and other disease... - Evidence consistent with human L1 retrotransposition in maternal meiosis IBrook Brouha
Department of Genetics, University of Pennsylvania School of Medicine, 475 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA
Am J Hum Genet 71:327-36. 2002..Since the mother carries a potential precursor allele and the insertion was on the patient's maternal X chromosome, it is highly likely that the insertion originated during maternal meiosis I... - Hot L1s account for the bulk of retrotransposition in the human populationBrook Brouha
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 100:5280-5. 2003..Thus, our data indicate that most L1 retrotransposition in the human population stems from hot L1s, with the remaining elements playing a lesser role in genome plasticity... - Recombinant canine B-domain-deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A modelDenise E Sabatino
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
Blood 114:4562-5. 2009..These data establish the framework to quantitatively investigate the efficacy and safety in preclinical studies of novel therapies for hemophilia A... - L1 retrotransposon-mediated stable gene silencingNuo Yang
Department of Genetics, University of Pennsylvania Philadelphia, PA 19104, USA
Nucleic Acids Res 33:e57. 2005..Our system provides a novel strategy for stable gene silencing that is easy and efficient, and it may have potential applications for ex vivo and in vivo molecular therapy... - SnapShot: Vertebrate transposonsPrabhat K Mandal
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Cell 135:192-192.e1. 2008 - SVA elements are nonautonomous retrotransposons that cause disease in humansEric M Ostertag
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6145, USA
Am J Hum Genet 73:1444-51. 2003..SVA elements, like Alus and L1s, occasionally insert into genes and cause disease. Furthermore, SVA elements are probably mobilized in trans by active L1 elements... - Progress in understanding the biology of the human mutagen LINE-1Daria V Babushok
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6145, USA
Hum Mutat 28:527-39. 2007..Finally, we discuss the role of L1 as a mutagen, using the latest findings in L1 biology to illuminate molecular mechanisms of L1-mediated gene disruption... - L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cellsNuo Yang
Department of Genetics, University of Pennsylvania School of Medicine, Rm. 475 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
Nat Struct Mol Biol 13:763-71. 2006..L1-specific siRNAs are among the first natural siRNAs reported in mammalian systems. This work may contribute to understanding the regulatory role of abundant antisense transcripts in eukaryotic genomes... - Extensive individual variation in L1 retrotransposition capability contributes to human genetic diversityMaria del Carmen Seleme
Department of Genetics, Division of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 103:6611-6. 2006..These data suggest that individual variation in retrotransposition potential makes an important contribution to human genetic diversity... - L1 integration in a transgenic mouse modelDaria V Babushok
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
Genome Res 16:240-50. 2006..We propose a unified model of L1 integration that explains all of the characteristic features of L1 retrotransposition, such as 5' truncations, inversions, extra nucleotide additions, and 5' boundary and inversion point microhomologies... - The L1 retrotransposition assay: a retrospective and toolkitSanjida H Rangwala
Department of Genetics, University of Pennsylvania School of Medicine, 564 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA
Methods 49:219-26. 2009..Finally, we provide detailed protocols on the application of the retrotransposition assay, including lists of constructs available in the L1 research community and cell lines in which this assay has been applied... - Dual vectors expressing murine factor VIII result in sustained correction of hemophilia A miceCathryn Mah
Department of Pediatrics, Department of Molecular Genetics and Microbiology, and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610-0266, USA
Hum Gene Ther 14:143-52. 2003..Because the murine form of the gene was used in the mouse model, less than 1 Bethesda unit of inhibitors was noted. This work demonstrates the feasibility of using rAAV vectors for the long-term treatment of hemophilia A... - Mobile elements and mammalian genome evolutionPrescott L Deininger
Department of Environmental Health Sciences, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
Curr Opin Genet Dev 13:651-8. 2003.... - L1 retrotransposition in nondividing and primary human somatic cellsShuji Kubo
Department of Medicine, UCLA School of Medicine, 675 Charles E. Young Drive South, MRL-1551, Los Angeles, CA 90095-7019, USA
Proc Natl Acad Sci U S A 103:8036-41. 2006..Thus, these data indicate that L1 retrotransposition can occur in nondividing somatic cells... - Genetics: LINEs in mindEric M Ostertag
Nature 435:890-1. 2005 - Phenotypic correction of a mouse model of hemophilia A using AAV2 vectors encoding the heavy and light chains of FVIIICiaran D Scallan
Avigen, Inc, 1201 Harbor Bay Parkway, Alameda, CA 94502, USA
Blood 102:3919-26. 2003..This strategy may potentially be useful for other large therapeutic proteins that contain functionally distinct domains... - Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia AIngrid Hrachovinova
The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115 USA
Nat Med 9:1020-5. 2003..This significantly improved the kinetics of fibrin formation in the hemophilia A mice and normalized their tail-bleeding time. P-sel-Ig treatment could become a new approach to sustained control of bleeding in hemophilia... - Two independent retrotransposon insertions at the same site within the coding region of BTKMary Ellen Conley
Department of Pediatrics, University of Tennessee College of Medicine, Memphis, Tennessee 38105, USA
Hum Mutat 25:324-5. 2005..A better understanding of the factors that make this site vulnerable will shed light on the mechanisms of LINE-1 mediated insertional mutagenesis... - Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolismRandy J Chandler
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Mol Genet Metab 89:64-73. 2006..elegans RNAi and deletion mutants... - Allelic heterogeneity in LINE-1 retrotransposition activitySheila M Lutz
Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109 0618, USA
Am J Hum Genet 73:1431-7. 2003..2A retrotransposition efficiency. Thus, common L1 alleles can vary widely in their retrotransposition potential. We propose that such allelic heterogeneity can influence the potential L1 mutational load present in an individual genome... - L1 retrotransposition can occur early in human embryonic developmentJosé A J M van den Hurk
Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Hum Mol Genet 16:1587-92. 2007..These findings provide evidence that L1 retrotransposition can occur very early in human embryonic development... - Lower inhibitor development in hemophilia A mice following administration of recombinant factor VIII-O-phospho-L-serine complexVivek S Purohit
Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, New York 14260 1200, USA
J Biol Chem 280:17593-600. 2005..Our results suggest that factor VIII-O-phospho-l-serine complex may be beneficial to increase the physical stability and reduce immunogenicity of recombinant factor VIII preparations...
Research Grants
- HUMAN TRANSPOSABLE ELEMENTHAIG KAZAZIAN; Fiscal Year: 2007..These studies will increase greatly our knowledge of the biology of L1 retrotransposition. In addition, they will provide important new information towards the effort to use L1 as a random insertional mutagen in mammals. ..
- Preclinical gene correction of hemophilia AHAIG KAZAZIAN; Fiscal Year: 2007..These results should make clinical trials with AAV vectors an appropriate next step. ..
- MEDICAL GENETICS RESEARCH TRAINING GRANTHAIG KAZAZIAN; Fiscal Year: 2007..This grant will fund up to three research years of the M.D. investigator in medical Genetics, and two years for M.D.-Ph.D. Fellows. ..
- HUMAN TRANSPOSABLE ELEMENTHaig H Kazazian; Fiscal Year: 2009..These studies will increase greatly our knowledge of the biology of L1 retrotransposition. In addition, they will provide important new information towards the effort to use L1 as a random insertional mutagen in mammals. ..
- Preclinical gene correction of hemophilia AHaig H Kazazian; Fiscal Year: 2010..These results should make clinical trials with AAV vectors an appropriate next step. ..
- Human variation in retrotransposon activityHAIG KAZAZIAN; Fiscal Year: 2007..Using this data, we will determine the extent of variation in L1 retrotransposition capability that exists among different individuals and geographic groups. ..
- MEDICAL GENETICS RESEARCH TRAINING GRANTHAIG KAZAZIAN; Fiscal Year: 2007..This grant will fund up to three research years of the M.D. investigator in medical genetics, and two years for M.D./Ph.D. fellows. ..
- HUMAN TRANSPOSABLE ELEMENTHAIG KAZAZIAN; Fiscal Year: 2006..These studies will increase greatly our knowledge of the biology of L1 retrotransposition. In addition, they will provide important new information towards the effort to use L1 as a random insertional mutagen in mammals. ..
- HUMAN TRANSPOSABLE ELEMENTHAIG KAZAZIAN; Fiscal Year: 2001..Lastly, they plan to initiate development of L1 elements into practical mutagenesis agents in mice. ..
- HUMAN TRANSPOSABLE ELEMENTHAIG KAZAZIAN; Fiscal Year: 2005..Thus, this focused proposal will provide answers to key questions of L1 biology and likely lead to a useful mutagenesis system for determination of gene function. ..
- FASEB Conference: Mamalian Mobile ElementsHAIG KAZAZIAN; Fiscal Year: 2005..Thus, this conference will allow investigators in these interrelated fields to share information about exciting new findings, experimental challenges, and outstanding questions in the area of mammalian mobile elements. ..
- HUMAN TRANSPOSABLE ELEMENTHaig H Kazazian; Fiscal Year: 2010..These studies will increase greatly our knowledge of the biology of L1 retrotransposition. In addition, they will provide important new information towards the effort to use L1 as a random insertional mutagen in mammals. ..