From genome-wide genetic discoveries to functional understanding and novel therapeutic targets for chronic lung diseases.
Scientists have used large genetic studies called genome-wide association studies (GWAS) to find hundreds of places in human DNA linked to a higher risk of chronic lung diseases. However, for most of these genetic regions, researchers still don't know which exact genes cause the disease, in which lung cell types, or how these changes lead to disease.
This research program aims to fill those gaps for three major lung diseases: Asthma, Chronic Obstructive Pulmonary Disease (COPD), and Idiopathic Pulmonary Fibrosis (IPF) — which affect millions of people and are strongly influenced by genetics.
Our projects combine many fields — genetics, genomics, bioinformatics, molecular biology, and machine learning — to move from genetic discoveries in humans to identifying novel drug targets and testing treatments in lung cell models.
Our laboratory focuses on three major chronic lung diseases that are strongly influenced by genetic variation.
COPD is one of the most prevalent and deadly chronic diseases worldwide, yet the mechanisms linking genetic risk to disease development remain poorly understood. GWAS have identified hundreds of loci associated with COPD risk and lung function, but the functional basis of most associations is unknown.
Our research characterizes chromatin 3D structure, regulatory DNA elements, and transcriptional regulation to annotate non-coding GWAS variants to coding genes in relevant lung cell types. We then validate causal variants by testing their effects on cellular biology in vitro and in vivo.
A key focus is on organelle-level disease mechanisms — particularly mitochondrial function and autophagy — which can be measured, grouped, and targeted with drugs, helping to discover new treatments via organoid drug screening.
Idiopathic Pulmonary Fibrosis is a devastating and progressive lung disease with limited treatment options. Our lab studies the genetic architecture of IPF, focusing on how common and rare genetic variants affect alveolar epithelial cells and fibroblasts in the lung.
We use human alveolar organoids as models to test repurposed drugs or novel drug targets that could treat IPF. These organoid systems recapitulate key aspects of alveolar biology, allowing us to measure disease-relevant phenotypes and conduct drug screening in a human cellular context.
Pathways of particular interest include RNA modification, innate immunity signaling, and cytoskeleton remodeling — all of which have been implicated in genetic studies of fibrotic lung disease.
Asthma affects hundreds of millions of people globally, with a complex genetic architecture involving hundreds of loci identified in large GWAS. Our lab studies the functional basis of asthma-associated variants, focusing on how they alter gene expression and cell biology in airway epithelial cells and immune cells relevant to asthma.
We apply integrative genomics approaches to connect genetic associations to specific genes and cell types, providing mechanistic insight into why certain individuals carry higher genetic risk for asthma.
We integrate cutting-edge experimental and computational approaches to connect genetic variants to disease biology.
Combining GWAS, eQTL, chromatin accessibility, and 3D genome maps to annotate non-coding variants to causal genes in relevant cell types.
Testing causal hypotheses using CRISPR editing, reporter assays, and RNA interference in disease-relevant human lung cell models.
Using human alveolar organoids to recapitulate lung disease biology and screen candidate therapeutics in a physiologically relevant setting.
Profiling gene activity in individual lung cells to understand cell-type-specific effects of genetic variation on disease pathophysiology.
Applying deep learning and statistical methods to predict functional variants, identify disease-relevant pathways, and discover new drug targets.
Validating key findings in in vivo models to confirm disease relevance and test therapeutic interventions before clinical translation.
An important part of our research program is training new scientists. Over the past decade, Dr. Zhou has mentored many graduate students, postdoctoral fellows, and junior researchers, several of whom have gone on to become independent scientists in universities or pharmaceutical companies across countries.
Continuous training in lung genetics and pulmonary disease research is increasingly important as more genetic discoveries lead to new drug development across a spectrum of human complex disease.
Join Our Lab