Proteoform Spatial Biology
Every cell in our bodies tightly controls the expression, localization, and interactions of proteins to control their functions. To do this, cells introduce amino acid sequence variations and posttranslational modifications (PTMs) at specific residues to produce families of unique molecules called proteoforms. Proteoform variation impacts human health and disease, such as by histone variations that classically affect chromatin packaging. We aim to build the first spatiotemporal blueprint of proteoform flux and decipher functional variations of proteins within human inflammation.
Research
Uncovering proteomic underpinnings of inflammation at the cell surface
The spatial distributions of proteins on immune cell surfaces is largely unknown. We will measure the dynamic topologies of immune cell surface proteins using a recently developed technique, Molecular Pixelation, to reveal cell surface protein colocalization changes that may present new spatial proteomic signatures of inflammation.
Dissecting the post-translational regulation of immune cells
Post-translational modifications like phosphorylation help to regulate cell signaling across many biological processes. We will use approaches like phosphoproteomics to investigate these processes in immune cells, and generate strong candidates for follow-up with proteoform studies and genetic perturbations.
Creating proteoform-resolved multiscale maps of immune cells
Measurements of proteoform identities, interactions, and spatial localization can be combined across scales using machine learning-based multimodal modeling. We aim to construct the first such proteoform-level multiscale cell map that will provide a data-driven map of cellular substructures that will enable broad usage of these data to better understand functional variation in autoimmunity.