Targeted single-cell analysis: In Ewing sarcoma, a pediatric/young-adult cancer of the bone and surrounding soft tissue, the EWS-FLI1 fusion oncoprotein expression level gives rise to metastatic versus proliferative cell subpopulations. We are uncovering the cytoskeletal signature of metastasis and studying cytoskeletal-targeting drugs. To do so, we develop single-cell fractionation assays for cytoskeletal complexes utilizing micro tumor models that mimic bone tumor microenvironments.

Cancer systems biology assay design: For many pediatric cancers, a single chromosomal re-arrangement results in a fusion oncoprotein with altered DNA and protein interactions that result in cancer progression. Understanding which sets of molecular interactions, or 'interactomes' underly proliferation and metastasis will reveal druggable phenotypes for investigation of novel therapies. We aim to innovate in the design of micro-scale protein separation materials and assays towards discovering the interactome of cell subpopulations present in Ewing sarcoma and other pediatric cancers.

Structural biology and biophysics nanotechnology: Fusion oncoproteins remain a challenging therapeutic target in pediatric cancers. Certain fusion oncoproteins comprise intrinsically disordered and DNA binding domains for which small molecule binding pockets have not been identified. Further, through interactions with chromatin remodeling complexes and phase separation into condensates, fusion oncoproteins alter the mechanics of gene expression. We are designing nano-scale systems for visualizing mechanical states and conformations critical to fusion oncoprotein biology. Our structural and mechanical insights will inform rational therapeutic design.