Emerging virus infections are a substantial global public health threat, in part due to the difficulties in responding to contain or treat previously unknown or uncharacterized pathogens. These emerging viruses can cause a diverse variety of disease phenotypes, ranging from mild subclinical infections to severe, highly lethal clinical manifestations such as hemorrhagic fever, encephalitis, and acute respiratory distress syndrome. The broad range of illnesses underscores the need for a framework enabling both rapid diagnosis and prognostic considerations to inform subsequent clinical and epidemiological strategies. Systems biology approaches complement classical methods for investigating emerging pathogens that depend on cultivation of the etiologic agent. By developing diagnostic and prognostic measures based on host responses to known and emerging pathogens, we can avoid issues associated with rapidly developing a robust experimental model for a new virus and substantially hasten the development of informed therapeutic strategies. Through close collaboration with other investigators in the center we plan to develop a reliable, comprehensive, and versatile platform for using host response signatures as diagnostic and prognostic tools. We plan to first use established disease models that are themselves based on emergent viruses, including both cell culture and animal models. Using signatures developed by computational integration of multiple datasets from models, we will apply these methods to newly emerging viruses. Finally, we will use our findings to mine existing drug databases to identify therapeutics that can be repurposed quickly and efficiently for treating these emerging diseases. In each of our Specific Aims, we will use high-throughput transcriptional profiling and novel non-linear geometric as well as machine learning computational methods to define genome-wide gene-activity biomeasures diagnostic of severe disease, prognostic indicators of disease outcome, and identify new potential host therapeutic targets for inducing antiviral effects and/or attenuating disease severity. In addition, we will garner new knowledge related to common and distinct mechanisms of pathogenesis and the host responses that determine eventual disease outcome.

Public Health Relevance

Emerging viruses are a major threat to global public health, particularly since there are few antivirals available to treat patients. There is a significant need for both methods to rapidly identify a newly emergent pathogen, but also to guide medical treatment and quickly develop therapeutic strategies to contain outbreaks and improve clinical outcome for patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI109761-01
Application #
8655271
Study Section
Special Emphasis Panel (ZAI1-LR-M (J1))
Project Start
Project End
Budget Start
2014-03-07
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$1,267,502
Indirect Cost
$243,332
Name
Columbia University
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Lindow, Janet C; Wunder Jr, Elsio A; Popper, Stephen J et al. (2016) Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLoS Pathog 12:e1005943
Bouilly, Delphine; Hon, Jason; Daly, Nathan S et al. (2016) Single-Molecule Reaction Chemistry in Patterned Nanowells. Nano Lett 16:4679-85
Bacharach, Eran; Mishra, Nischay; Briese, Thomas et al. (2016) Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of Tilapia. MBio 7:e00431-16
Beall, Anne; Yount, Boyd; Lin, Chun-Ming et al. (2016) Characterization of a Pathogenic Full-Length cDNA Clone and Transmission Model for Porcine Epidemic Diarrhea Virus Strain PC22A. MBio 7:e01451-15
Forero, Adriana; Tisoncik-Go, Jennifer; Watanabe, Tokiko et al. (2016) The 1918 Influenza Virus PB2 Protein Enhances Virulence through the Disruption of Inflammatory and Wnt-Mediated Signaling in Mice. J Virol 90:2240-53
Tisoncik-Go, Jennifer; Gasper, David J; Kyle, Jennifer E et al. (2016) Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism. Cell Host Microbe 19:254-66
Warren, Steven B; Vernick, Sefi; Romano, Ethan et al. (2016) Complementary Metal-Oxide-Semiconductor Integrated Carbon Nanotube Arrays: Toward Wide-Bandwidth Single-Molecule Sensing Systems. Nano Lett 16:2674-9
Strouts, Fiona R; Popper, Stephen J; Partidos, Charalambos D et al. (2016) Early Transcriptional Signatures of the Immune Response to a Live Attenuated Tetravalent Dengue Vaccine Candidate in Non-human Primates. PLoS Negl Trop Dis 10:e0004731
Menachery, Vineet D; Yount Jr, Boyd L; Sims, Amy C et al. (2016) SARS-like WIV1-CoV poised for human emergence. Proc Natl Acad Sci U S A 113:3048-53
Tokarz, Rafal; Sameroff, Stephen; Hesse, Richard A et al. (2015) Discovery of a novel nidovirus in cattle with respiratory disease. J Gen Virol 96:2188-93

Showing the most recent 10 out of 32 publications