Investigating the origins, evolution, and fundamental biology of pathogens is one of our high priority research areas with extraordinary potential for immediate impact.
Example Project: Hepatitis C and miRR-122 gene research
The Hepatitis C Virus (HCV) is widespread. It affects over 3 percent of the world’s population and more than 3 million people in the United States alone. HCV infections are on the rise among young people and increasingly the cause of death among baby boomers. New treatments have been launched but their extremely high prices are prohibitive for widespread use.
Our team has uncovered important new insights that reveal how HCV can evade emerging therapeutics, and about how the virus may cause liver cancer. Previous work had found that in order to infect cells, HCV requires that the cells express the gene miR-122. Drugs that inhibit miR-122 were shown to reduce HCV replication in patients. However, Sinai scientists discovered that HCV could evolve specific genetic mutations that enable it to replicate in cells even when the miR-122 gene is inhibited. Unexpectedly, they also found that the HCV virus itself hijacks the miR-122 gene, diminishing its normal activity in liver cells. Since this gene is known to be a potent tumor repressor, the findings suggest that HCV robs cells of their natural defenses against uncontrolled growth. Such an outcome could contribute to cancers that arise from chronic HCV infection.
The new found information could be used for more effective dosing of drugs to treat HCV, as well as for pre-treatment analysis to determine which patients may respond best to this class of drugs. The findings may contribute to more effective development of HCV drugs in the future and to more personalized treatment for patients. The information may also shed light on the link between HCV and the onset of cancer. From this study there are broader implications for this class of microRNA genes and their interaction with targets, which may be useful for a number of diseases in addition to viral Hepatitis.
- Nature: Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors
- Gen News Highlight: Hepatitis C Antiviral Resistance Revealed
Example Project: E. coli outbreak
Key members of our team pioneered the new era of rapid and comprehensive characterization of new pathogens during the deadly outbreak of E. coli in Germany in 2011. That outbreak affected thousands of people, with 50 killed and nearly 1,000 suffering kidney failure from hemolytic-uremic syndrome. We collaborated with researchers from around the world to conduct DNA sequencing of the outbreak strain, along with 11 related strains, to provide the most detailed characterization of the outbreak strain and novel insights regarding the strain's evolutionary origins. Our investigative work has continued, applying state-of-the-art analytics, and we published our findings in Nature Biotechnology. We found that chemical modifications to the DNA (known as "epigenetics") of the E. coli outbreak strain play a key role in regulation of gene expression, impacting the key processes of the bacterium's reproduction and virulence. These novel insights offer promising avenues for therapy development to help prevent and treat future outbreaks.
As we've done with E. coli, we will support global health efforts by investigating major pathogens (e.g., MRSA, malaria, cholera) and drive greater understanding of every aspect of the fundamental biology, from the genome to strain evolution, host interaction, societal influence and environmental impacts. We expect our unique analytical capabilities will provide new insights and pave the way for new diagnostics, vaccine development, and treatments.
Scientists Discover Complex Gene Regulation Mechanisms in the E. Coli Pathogen Responsible for a Deadly 2011 Outbreak in Germany: Discovery of role of epigenetic modifications provides new approach to fully characterize pathogens that could help develop new treatments.