Transformative Resarch Award (TR01) — Extent & Significance of Bacterial DNA Integrations in the Human Cancer Genome.

The integration of exogenous DNA into the human genome can cause somatic mutations associated with oncogenesis. For example, the insertion of HPV DNA into human chromosomes is the single most important event leading to tumorigenesis in cervical cancer. It is also now preventable with vaccines against HPV. In contrast to viral DNA integrations, the instances and repercussions of bacterial DNA integration into the somatic human genome are less clear.  This project has three objectives aimed at addressing our gap in knowledge about bacterial DNA integrations. First, virtual machines will be developed for LGTSeek and LGTview, our bioinformatics tools that we have used previously to detect bacterial DNA integrations in human genome sequencing projects. LGTSeek and LGTView will be used to further interrogate publicly available cancer genome data where such integrations are likely to occur because the tissues are exposed to the microbiome (e.g. colon). Second, genome and transcriptome sequencing will be undertaken of new stomach adenocarcinoma samples and acute myeloid leukemia samples in order to reproduce previous results that suggest the presence of bacterial DNA integrations, includinge control samples with exogenous bacterial nucleic acids added to the sample in order to quantify the formation of chimeras in modern sequencing techniques. Third, the effect that previously detected bacterial DNA integrations have on transcription will be interrogated using luciferase reporter constructs and the CRISPR/Cas9 system. Collectively, this research is expected to improve our understanding of the extent and significance of bacterial DNA integrations in the somatic human genome.

NSF-funded: ABI: Development: Cloud-based Identification and Visualization of Lateral Gene Transfers in Genome Data

All genomes accumulate mutations that are both beneficial and detrimental to the organism. The best understood mutations are those that involve alteration, insertion, or deletion of a single base pair, where there are numerous tools for identifying and validating such changes. Yet in many organisms, it is increasingly appreciated that large, even massive, insertions of DNA can occur from other organisms, termed lateral gene transfer, that have the potential to have a profound effect on the organism, either detrimental or beneficial. For example, large insertional mutations led to the transition of endosymbionts to organelles like mitochondria and chloroplasts. This project seeks to improve tools previously developed to identify such lateral gene transfers from genome sequencing data, and to make these tools available to the research community after ensuring that they are more robust and user friendly. In addition, this proposal seeks to develop YouTube whiteboard videos to educate the general public about these mutations, genomics, and the tools developed in this proposal.

NIAID-funded Genome Center for Infectious Disease Co-Project Leader — Integrated Genomics Research in Parasitic Tropical Diseases — Lymphatic Filariasis Subproject

Parasitic diseases impose a tremendous toll on the global public health. Malaria causes up to 1.24 million deaths every year, while human filariasis is a neglected tropical disease that remains a major cause of disability in the developing world. This subproject focuses on the filarial nematode Brugia malayi, which causes lymphatic filariasis. Population genomics, multi-species transcriptomics, and whole genome sequencing are used to improve our understanding of the organisms responsible for this important neglected tropical disease.


NIAID-funded Genome Center for Infectious Disease Core Leader — Technology Core

Genomics has revolutionized research into infectious diseases and is poised to revolutionize the clinic. Through the activities in this technology core, we provide high-throughput genome sequencing and analysis focused on understanding host, pathogen, and microbiome interactions as determinants of disease outcome. We provide state-of-the-art, large-scale, high-throughput sequencing data for analysis of genomes, transcriptomes, metagenomes, metatranscriptomes, and microRNAs using the best methodologies and technologies available. 

While we do not currently have funded projects on these topics, we have also worked on:

  • LGT in D. ananassae
  • LGT in B. malayi
  • Genomics of Neisseria meningitidis
  • Genomics of Human Ehrlichiosis Agents
  • Brown Marmorated Stinkbug Transcriptome
  • Dung Beetle Microbiome