We are a structural biology lab that uses a plethora of structural, biochemical, biophysical, cell biology, and human samples to develop a mechanistic understanding of healthy homeostasis and disease pathogenesis.
Some of our current projects:
The Roles and Mechanisms of CLCA Channel Modulators in Mucosal Immunology
Disease relevance: Cystic Fibrosis, Asthma, COPD, Crohn’s, Ulcerative colitis, cancer
Ion channels and their modulators play critical, yet poorly understood, roles in health and disease by influencing secretion and mucus function. Our work in the area has mainly focussed on the Calcium-Activated Chloride Channel Regulator (CLCA) family of proteins. This family of proteins has long been linked to human diseases, but little is known regarding their functions or role in disease. We have developed a number of biochemical and structural tools to investigate this family. We have shown that the secreted CLCA1 is a potent and specific potentiator of the calcium-activated chloride channel TMEM16A. Current work focuses on mechanistic and translational applications, as well as the roles of other human CLCA family members.
The Functions and Mechanisms of Genetic Risk Factors in Neurodegenerative Diseases
Disease relevance: Alzheimer’s disease (AD), Parkinson’s disease (PD), Frontotemporal Dementia (FTD)
Understanding the molecular mechanisms that underlie the development of Alzheimer’s disease (AD) are key to developing safe and effective therapies. In recent years, genetic studies have identified risk variants in a number of novel genes that greatly increase the risk for developing late-onset AD. However, the role of the encoded proteins in neuronal health and the molecular impacts of these variants is not well understood. Our work has focussed mainly on proteins linked to neuroinflammation, including TREM2 and modulators such as MS4A4A. Our structural and mechanistic work will provide the framework to develop therapeutics targeting these novel AD targets.