UCSF - The Prusiner Laboratory - Overview

The Prusiner Laboratory
We are a world-class research facility focused on understanding neurodegenerative diseases caused by protein misfolding. We are part of the Institute for Neurodegenerative Diseases at the University of California, San Francisco. Our primary focus is on prion diseases (e.g., Creutzfeldt-Jakob Disease (CJD) and bovine spongiform encephalopathy or "mad cow disease"), with the aim of understanding the biological basis of these diseases, developing effective diagnostics and therapeutics, and improving patient and food safety by inactivating prions.

The Molecular Basis of Prion Disease
We are interested in the structure of the prion protein and how it causes disease. Through methods such as spectroscopy, electron microscopy, fiber diffraction and crystallization, we can learn about the structure of the prion protein in its normal and disease-causing form, and the transition between the two. Understanding this will allow us to develop better diagnostic tools and therapeutics.

Diagnostics
The early symptoms of CJD and other prion diseases are not well defined and are frequently confused with other less devastating conditions. Consequently, by the time patients are diagnosed with CJD, the disease has usually progressed and caused widespread brain damage. We are engaged in an effort to develop a rapid and sensitive test able to detect human prions in the earliest possible stages of disease. Simply halting the progression of prion disease may not restore lost central nervous system function, and therefore, a clinical test for the earliest possible diagnosis is essential. A preclinical diagnostic test is critical to the success of developing a drug therapy for CJD and other prion diseases.

Therapeutics
We are developing novel therapeutics against prion diseases by applying our molecular understanding of prion biology. We have already identified several promising classes of prion inhibitors. Our current work is optimizing these drugs and discovering new inhibitory compounds that have novel modes of intervention. The knowledge gained by our prion therapeutics efforts will undoubtedly provide valuable insights into treating other protein misfolding disorders.

Prion Inactivation
Infectious prions bind tightly to stainless steel surfaces and are not inactivated by standard hospital sterilization techniques. Reuse of contaminated surgical instruments can lead to iatrogenic transmission of CJD to subsequent patients. Similarly, instruments used in processing of prion-infected animals for food could spread infectivity to prion-free meat if they are not properly decontaminated. We are developing methods to inactivate prions, and validating them with highly sensitive transgenic models.