James Shorter

James Shorter is a Professor of Biochemistry and Biophysics at the Perelman School of Medicine, University of Pennsylvania. He is affiliated with multiple prestigious institutes, including the Institute on Aging (IOA), the Institute for Translational Medicine and Therapeutics (ITMAT), the Penn Center for AIDS Research (CFAR), the Chemistry-Biology Interface (CBI), and the Penn Institute for RNA Innovation. He mentors several training programs such as the Penn Summer Undergraduate Internship Program (SUIP), PennPREP, and the Translational Research Immersion Program (TRIP), and serves as a Primary Trainer at the Center for Neurodegenerative Research (CNDR).

• Ph.D. in Cell Biology, University of London, 2000
• M.A. in Biology, University of Oxford, 1995

Dr. Shorter’s research focuses on protein homeostasis, particularly the mechanisms of protein disaggregation and the role of prion-like domains in neurodegenerative diseases such as ALS, Alzheimer’s, Parkinson’s, and frontotemporal lobar degeneration. His lab investigates the Hsp104 disaggregase from yeast and has engineered variants to combat human proteinopathies. They also identified the mammalian disaggregase system (Hsp110/Hsp70/Hsp40) and explore how small molecules and nuclear import receptors can reverse pathological phase transitions of RNA-binding proteins like TDP-43 and FUS. His work bridges structural biology, genetics, and translational neuroscience.

His recent publications highlight trends in targeting TDP-43 and FUS proteinopathies, engineering Hsp104 for selective detoxification, understanding mitochondrial disaggregases like Skd3, and modulating phase transitions with nuclear import receptors. His research spans from fundamental mechanisms of protein folding to therapeutic development for neurodegenerative diseases.

• Faculty Member, Institute on Aging (IOA)
• Faculty Member, Institute for Translational Medicine and Therapeutics (ITMAT)
• Mentor, Penn Summer Undergraduate Internship Program (SUIP)
• Primary Trainer, Center for Neurodegenerative Research (CNDR)
• Faculty Member, Penn Center for AIDS Research (CFAR)
• Member, Penn Institute for RNA Innovation
• Mentor, Translational Research Immersion Program (TRIP)

Dr. Shorter advises numerous graduate students and postdoctoral researchers through the Biochemistry and Molecular Biophysics, Pharmacology, Neuroscience, and Cell and Molecular Biology graduate groups. His lab receives funding from NIH and other sources to support research on protein disaggregation, phase separation, and neurodegenerative disease mechanisms. He has trained many scientists now active in academia and biotech.

His lab, located in Stellar-Chance Laboratories, operates at the intersection of biochemistry, cell biology, and translational medicine, with active projects on Hsp104 engineering, mitochondrial proteostasis, and the role of RNA-binding proteins in disease. The lab collaborates widely across Penn and with international partners to advance understanding and treatment of protein misfolding disorders.