Robert Guzy, MD, PhD

APPOINTMENTS

  • Assistant Professor, Department of Medicine, Section of Pulmonary/Critical Care, Committee on Cancer Biology

EDUCATION

Ph.D., University of Chicago, 2005
M.D., University of Chicago, 2008

CONTACT INFORMATION

rguzy@uchicago.edu

RESEARCH SUMMARY

Cell-Specific Functions of Fibroblast Growth Factor Signaling in Lung Injury and Pulmonary Fibrosis

Lung alveolar epithelial cell (AEC) injury is caused by a variety of insults, and in severe cases causes respiratory failure and Acute Respiratory Distress Syndrome (ARDS).  Chronic or repeated AEC injury is also central to the pathogenesis of Pulmonary Fibrosis, as repeated injuries and aberrant AEC repair leads to inappropriate activation of fibroblasts and deposition of extracellular matrix. Unfortunately, outcomes in both ARDS and IPF are poor, and there are limited pharmacologic treatments.  My goal is to employ genetic tools in the mouse to understand the mechanisms regulating how lung epithelium, endothelium, and fibroblasts interact to promote 1) repair following lung injury and 2) pathological fibroblast proliferation resulting in a variety of lung diseases, including pulmonary fibrosis.

I study Fibroblast Growth Factor (FGF) and FGF receptor signaling, as well as other signaling molecules that interact with FGFs.  FGFs, together with their high affinity receptors, constitute a complex signaling pathway involved in cell growth, differentiation, recovery from injury, fibrosis, and neoplasia. FGFs directly interact with other signaling molecules including BMPs, BMP inhibitors such as Gremlin, hedgehog proteins, PTHrP, and WNTs.  The importance of FGFs in Pulmonary Fibrosis has been underscored by the FDA approval of a novel antifibrotic agent (Nintedanib) that targets the FGF pathway.  Despite this, the cellular mechanism through which FGF signaling contributes to Pulmonary Fibrosis is not understood and warrants continued investigation.  

My research examines the role of FGFs and FGF receptors in response to lung injury and in the pathogenesis of pulmonary fibrosis.  I employ cell-specific inducible loss-of-function and gain-of-function mouse models in combination with standard lung injury models to study injury and repair in lung airways or in the alveolar space.   The physiological and pathophysiological consequences of FGF/FGFR loss-of-function or gain-of-function are explored with the aim of understanding whether FGFs can be utilized as a restorative growth factor following lung injury, and how FGF signaling is required for the pathogenesis of pulmonary fibrosis.