Identifying Modifiers of Rhinovirus-Induced Pathological Inflammation to Combat Asthma

Identifying the signaling pathways that drive rhinovirus-induced airway inflammation to find small molecule drugs that prevent asthma attacks.
Ongoing Allergic & Atopic Diseases Biological & Mechanistic Cytokine Signaling Experimental Platforms & Models In Vitro Models Innate Immunity Organoids Therapeutic Development Translational & Clinical

Funding Year: 2024

Project Overview

Common cold viruses are the most frequent triggers of asthma attacks, yet people with asthma mount abnormally pathological immune responses to these viruses. This project uses new experimental models — combining purified viruses with lab-grown human airway tissue — to replicate these abnormal responses and identify the signaling pathways that mediate them. A high-throughput screening assay developed by the team is being used to identify small molecules capable of blocking these pathological responses to rhinovirus. Together, these advances aim to produce drug candidates that prevent asthma attacks, with safety and efficacy testing in animals and healthy humans as the next clinical development step.

Impact & Innovation

Blocking the cold virus pathway that triggers asthma.

 

Using lab-grown human airway tissue and purified rhinoviruses, this project maps the abnormal signaling driving asthma attacks and screens small molecules to block it — moving from mechanism to drug candidate in a single pipeline.

  • Identifies alternative signaling pathways activated by rhinovirus in asthmatic airways as novel therapeutic targets for asthma attack prevention
  • Generates IP potential through a high-throughput screening assay and provisional patent anticipated from screen results and validation experiments
  • Advances the Consortium’s From Mechanistic Insight to Translation pillar by connecting airway immune dysregulation to a structured drug discovery and preclinical development pipeline
Research Approach

A framework designed for discovery

This project combines experimental airway tissue modeling with pathway analysis and high-throughput small molecule screening to identify and validate drug candidates that block rhinovirus-induced pathological inflammation in asthma. The work moves from mechanistic discovery through screening and preclinical candidate development.

New experimental models using purified rhinoviruses and lab-grown human airway tissue to replicate abnormal asthmatic immune responses; signaling pathway analysis to identify mediators of pathological inflammation; and a high-throughput screening assay to identify small molecules that block rhinovirus-activated pathological pathways.

Lab-grown human airway tissue models exposed to purified rhinoviruses, signaling pathway datasets identifying mediators of pathological vs. normal cold virus responses, and high-throughput small molecule screening datasets with validation experiments to confirm candidate activity.

Identification and validation of small molecule candidates that block rhinovirus-induced pathological airway inflammation, with next steps including safety testing in animals and healthy human subjects and efficacy testing during RV-positive asthma exacerbations. A provisional patent is anticipated from screening results and validation data.

Investigators & Institutions

Powering the science

Colton Centers & Institutions

Colton Center for Autoimmunity at Yale University