Daniel Southworth

Dr. Daniel Southworth is a Professor in the Department of Biochemistry and Biophysics at the University of California San Francisco (UCSF), affiliated with the Institute for Neurodegenerative Diseases (IND). He earned his BS from UC Santa Cruz and PhD from Johns Hopkins University, followed by postdoctoral training at UCSF. His research focuses on molecular chaperones and protein quality control mechanisms relevant to neurodegenerative diseases like Alzheimer’s and Parkinson’s. Using cryo-electron microscopy (cryo-EM), his lab investigates chaperone machinery structure-function relationships, amyloid aggregation pathways, and therapeutic strategies targeting molecular chaperones.

Key research areas include: (1) Structural biology of chaperones like Hsp90, CHIP, and Hsp104; (2) Mechanisms of tau and α-synuclein aggregation; and (3) Development of cryo-EM techniques for studying protein complexes. Recent work has revealed novel filament structures in neurodegenerative diseases and identified polyphosphate’s role in amyloid formation.

His lab pioneered studies on VCP/p97 AAA+ ATPases and their adaptors, elucidating their roles in protein quality control. Collaborations include CRISPR-based screening in iPSC-derived neurons and drug design targeting chaperone-driven proteostasis.

Notable contributions include cryo-EM structural analysis of SARS-CoV-2 proteins and methodological advancements in cryo-EM imaging using K3 cameras. Current research emphasizes translating structural insights into therapeutic approaches for neurodegenerative disorders.