Overcoming Monocyte Complexity in Pulmonary Fibrosis Progression from Onset to End-Stage

Introduction

Progressive pulmonary fibrosis (PF) is a debilitating and incurable disease. Scarring of the lung leads to respiratory failure, and 50% of patients die 3-5 years after diagnosis. Our understanding of the pathophysiology of PF is unfortunately limited to established and advanced stages when the extensive lung scarring is irreversible.

Project Overview

OMEGA is designed to explore new mechanisms underlying PF progression, from early to advanced disease, and propose therapies that timely target the disease before it becomes permanent. Two lines of evidence are at the core of OMEGA:

1. I was among the first to show that circulating monocytes are strongly linked to PF pathology. However, which subtypes are important and what roles they play in PF etiology is still unknown.
2. Interstitial lung abnormalities (ILA) are the only detectable features characterizing earlier stages of PF and can be identified in people without clinical suspicion of disease. Studying ILA provides the unique opportunity to identify early targets that would prevent progression to PF.

Research Objectives

OMEGA will first provide a detailed phenotype definition of human monocyte subtypes from early to advanced PF.

Second, it will probe mechanistically how and where the monocytes acquire a pathogenic phenotype as they journey from the bone marrow to the blood and differentiate in the fibrotic lung.

Methodology

I will use human and mouse material and state-of-the-art methodology to answer these questions. My current standing ensures direct and ample access to patient samples, clinical data, multi-disciplinary interactions, and a team of consultants/collaborators.

Goals

This collaboration will make it possible to identify how monocytes and their progenitors are involved in the progression of PF, and what pathways we can target as early as the disease starts, and as early as monocytes egress the bone marrow, to end the progression of this deadly disease.