Smriti Sangwan, PhD
Assistant Professor, Pharmacology
Research Program
Cancer-Focused Research
Our lab focuses on understanding the molecular basis of protein quality control. Protein quality control is critical for cellular health and is constantly monitored via signaling systems to ensure that all proteins fold correctly and are delivered at the correct location. Stress conditions such as pathogenic infections, hypoxia and protein misfolding can impact protein homeostasis. Our cells respond to such stressors by activating different signaling systems such as the unfolded protein response (UPR) at the ER and the heat shock response in the cytoplasm along with translational remodeling. The transient nature of these pathways enables rapid activation and deactivation upon recovery of homeostasis. However, the transient nature has also rendered their characterization to indirect means and molecular information has been elusive. We combine state-of-the-art structural tools including functionalized microscopy grids, cryo-electron microscopy (cryoEM) and cryo-electron tomography (cryoET) with biochemical, sequencing, and computational methodologies to obtain molecular details of protein quality control, and its dysfunction in disease conditions. By mapping how these systems function, we aim to identify new therapeutic targets for a range of diseases, including neurodegenerative disorders, cancer, and metabolic diseases.