Investigating Molecular Mechanisms of Gene-Environment Interplay in Complex Diseases

Complex diseases are multifactorial disorders caused by interacting genetic and environmental factors. Our laboratory is primarily interested in understanding the mechanisms underlying the interplay between genes and environmental exposures in complex diseases such as asthma and atopic dermatitis. We integrate classical and modern tools in molecular and cell biology, biochemistry, and functional genomics, along with animal models, to explore these molecular processes. Through this integrative approach, we aim to advance our understanding of the molecular basis of asthma and other complex diseases, which could open doors for the development of novel therapeutic strategies.

Our current work focuses on the functional role of gasdermins, in particular gasdermin B (GSDMB), in asthma. Asthma is a complex disease of the airways and the mechanisms driving disease progression are poorly understood. A hallmark of allergic diseases like asthma is epithelial barrier dysfunction. We believe that one key mechanism contributing to this dysfunction is pyroptosis, a highly inflammatory cell death mechanism mediated by gasdermins. Yet, the distinct pathways that trigger pyroptosis in the airways and how they contribute to epithelial dysfunction and allergic phenotypes, are still unknown. Focusing on the GWAS prime candidate asthma gene, GSDMB, we are studying the molecular processes regulating GSDMB-mediated pyroptosis in airway epithelial cells and how these processes contribute to asthma pathogenesis.

An emerging focus of our research is examining how environmental contaminants (e.g. polycyclic aromatic hydrocarbons) contribute to cellular alterations associated with asthma and COPD. These contaminants are public health concerns as they are widespread in the environment. We are investigating how these environmental contaminants drive changes in cellular functions that may contribute to the development of lung diseases.