Research Overview

Viral infections have a tremendous impact on human health, yet little is known about the interactions between the pathogen and its host. We, therefore, propose a Systems Biology Approach to analyze virus infections in different biological systems, identify pathogen-host interactions, characterize host cell responses, and correlate these data with bioinformatics approaches. Influenza viruses are an ideal model system due to their impact on human health and the global economy. A ‘Virology/Cell Biology Unit’ will characterize influenza viral replication and pathogenicity in cells and animals and identify host-virus interaction partners. A ‘Host Cell Response Unit’ will study the cellular transcriptome in response to viral infection. An 'Immunology Unit' will analyze the mechanism of anti-viral immune responses and respiratory inflammation in the animals infected with influenza virus. Data analysis and modeling of cellular responses will be conducted by the ‘Computational Systems Biology Unit’. These studies will lead to a comprehensive understanding of the cellular networks activated upon viral infections and are, therefore, expected to establish new concepts in study of viral diseases.

Major Research Topics

Identifying the host factors and their role in influenza virus infection

Influenza viruses utilize the host cellular function to support their life cycle. Therefore, identification of host-viral interactions in viral replication is of interest to understand the molecular mechanisms of the influenza virus life cycle and to find new targets for the development of antiviral compounds. To understand the role of host-viral interactions in influenza virus replication, we have constructed the most comprehensive database, to date, using data mined from literature as well as novel interactions identified in our lab. We then integrate this knowledge into known signaling pathways in host cells to create a comprehensive mapping of host-virus interactions. With this map, we can address (1) which host pathways may directly impact the health and survival (2) identify pathways and factors important for virus replication (3) search for sets of interactions which may explain patient-to-patient variability and more.

Analysis of the host response to influenza virus infections

Analysis of the host response to influenza virus infections Why one influenza virus strain is more pathogenic than another is still an open question in virology. One factor is the distinct responses different virus infections invoke in the hosts. Thus, one major area of study in our group is classifying the various genomic and proteomic responses invoked by different viruses to better understand which host response mechanisms may be responsible for high pathogenicity in the hosts.

Assessing the pandemic potential of circulating Influenza viruses

The swine-origin H1N1 virus that emerged in Mexico in the spring of 2009 [A(H1N1)pdm2009] caused the first influenza pandemic of the 21st century. To understand the mechanisms of the emergence of pandemic influenza viruses, we have conducted 1) the characterization of the A(H1N1) pdm2009 virus in vitro and in vivo, 2) the molecular analyses to clarify the
mechanisms of the emergence of reassortant viruses, 3) the risk assessment of pandemic potential of highly pathogenic H5N1 avian influenza viruses. The results obtained from our study would provide useful information for crisis management and public health management during the next pandemic.

Development of in-silico technology platforms to facilitate data processing and integration

In this study, we aim to elucidate the “whole picture” of the host response. Following the systems biology mantra, we developed a map of the virus-host interactome (described above) which we can than analyze using control engineering and network tools to identify novel therapeutic strategies. This work is done in collaboration with the Systems Biology Institute (SBI), Tokyo, and the tools developed plays important supportive roles in many aspects of our groups research. Please see Resources for publically available platforms.