Some ongoing research projects are described in news articles (linked here).
Our research focuses on understanding how cells stick or unstick from each other, a process that is important for understanding how tissues form, how wounds heal and how cancer cells metastasize. Transmembrane proteins called cadherins, enable cells to adhere together and we are pioneers in resolving the molecular basis for cadherin interactions and developing approaches to engineer cadherin adhesion. For instance, our group showed for the first time that cadherins adopt different conformations with distinctly different adhesive properties and tune adhesion by switching between these conformations . Recently, we also directly resolved, at the single molecule level, how cytoplasmic proteins regulate cadherin conformation and adhesion. Ongoing projects in the lab include:
- Determining molecular basis for the assembly and adhesion of desmosomes: Desmosomes are essential adhesive organelles present in tissue like the heart and skin, which are exposed to mechanical stress. We are studying the mechanistic basis for the assembly and organization of desmosomes.
- Developing antibodies to tune cadherin adhesion for therapeutic applications: We are rationally engineering monoclonal antibodies to modulate cell-cell adhesion, for potential applications in reducing cancer metastasis.
- Developing technologies to discover novel cadherin binding partners: We are developing novel proximity labeling approaches to map transmembrane proteins that interact with cadherins. We recently developed an optogenetic proximity labeling method that can be turned ‘on’ and ‘off’ using light and are currently developing methods to monitor cadherin dimerization on cell surfaces.
- Developing microscopy methods for discovering novel adhesive interactions in cells: We are developing an ultrasensitive microscope that can simultaneously measure interaction forces between single adhesive proteins and their corresponding force-induced conformational changes.