THE HUMAN MICROBIOME
DNA INTEGRATION IN
HUMAN GENE THERAPY
Research in the Bushman laboratory focuses on host-microbe interactions in health and disease, with particular focus on studies of 1) the human microbiome, 2) HIV pathogenesis, and 3) DNA integration in human gene therapy.
In recent years, our work has been driven increasingly by the remarkable new deep sequencing methods, which can produce more than 100 billion bases of DNA sequence information in a single instrument run.
For microbiome studies, this allows comprehensive analysis of microbial populations without reliance on culture-based methods, which can detect only a small fraction of all organisms present.
For studies of HIV replication, this allows analysis of complex viral populations or distributions of retroviral DNA integration sites in the human genome.
For gene therapy, this allows tracking of integrated vectors in gene-corrected subjects and molecular characterization of adverse events. Sample acquisition can sometimes be difficult in such projects, but bioinformatic analysis afterwards is almost always harder. We have been carrying out this type of study since 2002, when we showed that HIV DNA integration in human cells was favored in active transcription units, and over the years have built up partially automated software pipelines that allow efficient analysis deep sequencing data.
Lab members and collaborators cover a range of specialties, including clinical researchers, molecular biologists, computational biologists, and statisticians.
HIV Replication in LEGO Mosaic.
AIDS Res Hum Retroviruses.
AIDS Res Hum Retroviruses 2015
Multi-center Comparison of Lung and Oral Microbiomes of HIV-infected and HIV-uninfected Individuals.
Am J Respir Crit Care Med 2015
Power and sample-size estimation for microbiome studies using pairwise distances and PERMANOVA.
BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency.
Cell Host Microbe 2015
Alterations of the Subgingival Microbiota in Pediatric Crohn’s Disease Studied Longitudinally in Discovery and Validation Cohorts.