# Project 1 - Host-virus networks regulating flu replication and host responses in vivo

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $498,282

## Abstract

Influenza A virus is a major human respiratory pathogen, and available vaccines and antivirals are of
limited efficacy. In order to identify novel targets for therapeutic intervention during influenza virus infection, we
have assembled an interdisciplinary team that uses a highly integrated systems level approach to identify and
validate key genes/networks involved in virus pathogenesis. The overarching theme of our multidisciplinary
proposal “FluOMICS: The NEXT Generation” is to obtain multiple OMICS-based systems level measurements
and integrate them using modeling approaches and machine learning algorithms to identify and validate 1)
host-virus networks that modulate influenza A virus disease severity, 2) biomarkers in blood that reflect the
activation states of these networks and 3) novel host targets for therapeutic interventions. The proposed
studies leverage on our previous collaborations that generated global datasets and models that predict
severity of disease caused by three specific influenza virus strains with different levels of
pathogenicity. Our underlying main hypothesis is that host networks involved in viral replication and in early
host responses regulate disease outcomes and represent promising targets for therapeutic intervention. We
also propose that, in addition to the pathways identified in our previous collaboration, there are additional
distinct pathways that result in either resilience or pathogenic outcomes after influenza virus infection, and that
specific pathogenic pathways will require tailored therapeutic interventions. To identify networks associated
with clinical disease in humans, we propose to integrate into predictive and comprehensive models OMICS
responses during influenza virus infection in three systems 1) human blood from a human cohort of patients
with documented influenza virus infection and diverse clinical outcomes (Project 1, Aim 3); 2) mouse blood
and tissues from experimentally infected animals under a variety of conditions and perturbations resulting in
diverse disease outcomes (Project 1, Aim 1) and 3) relevant primary human cells experimentally infected
under controlled conditions and perturbations associated with diverse disease outcomes (Project 2). Samples
will be collected, processed and send to the Technology Core to conduct global transcriptomics, proteomics
and metabolomics analysis. OMICS data sets will be integrated and compared by the Modeling Core to
generate network models of disease, uncover blood biomarkers and identify key drivers as targets for
mechanistic studies and therapeutic intervention (Project 1, Aim 2). In summary, our systems modeling
approaches will find correlates and associations between diverse experimental systems that will help us define
human blood biomarkers, and link them to in vivo and ex vivo signatures for both companion diagnostics and
personalized therapies.

## Key facts

- **NIH application ID:** 10080713
- **Project number:** 5U19AI135972-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Adolfo Garcia-Sastre
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $498,282
- **Award type:** 5
- **Project period:** 2018-01-20 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080713

## Citation

> US National Institutes of Health, RePORTER application 10080713, Project 1 - Host-virus networks regulating flu replication and host responses in vivo (5U19AI135972-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10080713. Licensed CC0.

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