• What proteins ensure the quality control of various soluble or aggregated protein substrates?

• How do these quality control factors function?

• Can these factors be utilized for proximity-based therapies for neurodegeneration, cancer, or other diseases?

We develop novel ways to study protein function beyond genetic perturbation by directly perturbing proteins or protein-protein interactions. We use these tools to investigate the quality control of misfolded or unstable proteins to develop strategies for combating protein misfolding disorders. Our approaches include pooled protein tagging and high-throughput recruitment screens to identify "effector" proteins, alongside biochemistry and chemical biology techniques to understand their mechanisms and therapeutic potential.

• How do neuronal cell compartments maintain protein quality and function?

• What stress responses do compartments experiencing protein folding stress elicit?

• How do these mechanisms change in neurodegenerative diseases?

Our understanding of protein quality control mechanisms throughout the cell is limited, especially beyond well-studied compartments such as the ER. To address this, we generate a diverse pool of proteostasis substrates and analyze compartment-specific transcriptional and quality control responses using advanced single-cell technologies, such as single-cell RNA sequencing and in-situ sequencing.

• How does RNA contribute to maintaining protein homeostasis?

• Can specific transcripts be manipulated to control protein aggregation?

Despite the abundance of knowledge of RNA-protein interactions in cells, relatively little is known about the roles of RNA in protein quality control. We seek to uncover these novel mechanisms by developing technologies to study and manipulate the transcriptome in unique ways.

• How is protein quality maintained in the Golgi apparatus?

• How do mitochondria signal proteotoxic stress to the endoplasmic reticulum?

From our large-scale projects described above, we aim to unravel the mechanisms of the unique proteostasis pathways we discover, which is crucial for devising strategies to manage cellular stress responses and influence disease outcomes. We thus integrate high-throughput technologies with traditional biochemistry and cell biology to dissect these complex pathways.