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Qiuye Li, Ph.D.

Grant Title: “High-resolution structure determination of MM1 and MM2 sCJD prions”

Location: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH

Grant Year: 2023

Prion diseases are infectious fatal neurodegenerative diseases caused by misfolded, aggregated formed of the prion protein, often referred to as prions or PrPSc. The most common form of human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD) that presents itself as several subtypes, and the best characterized of those are the MM1 and MM2 subtypes. Earlier studies, including those from our lab revealed that all the phenotypic variation of MM1 and MM2 cases is closely related to (and likely encoded in) differences in structural organization of corresponding prions. However, this comparison was limited to very low-resolution studies, lacking crucial structural details. The recent development of cryo-EM methods for structural studies of other disease-related protein aggregates have revolutionized the field of prion structural biology, providing high-resolution structures of many pathogenic protein aggregates. Currently, no information is yet available about high-resolution structure of sCJD prions. In this study we aim to fill this critical gap in the field, by determining high-resolution structures of phenotypically well-characterized MM1 and MM2 sCJD prions. Such information is of fundamental importance not only for understanding the molecular basis of phenotypic variability of sCJD but also for the development of therapeutic approaches against human prion diseases.

About the Researcher:

Qiuye Li, Ph.D.
Department of Physiology and Biophysics, School of Medicine
Case Western Reserve University, Cleveland, OH

Dr. Qiuye Li received his PhD from Case Western Reserve University and now works there as a postdoc scholar in the Dr. Surewicz laboratory. His graduate research has been focused on biophysical and structural characterization of amyloid fibrils and synthetic prions, and now he mainly works on high-resolution structural determination of disease-related amyloid fibrils. One of his recent postdoctoral studies has provided insights into the structural basis of cross-species seeding specificity in prion propagation. Dr. Li is currently working on the structure determination of brain-derived prions including those isolated from sCJD patients. These molecular structures will provide a stepping stone for development of effective therapeutic strategies in human prion diseases.

Recipient of:

The Strides for CJD Research Grant

Contributed by: The Families of the CJD Foundation

Funds raised by the annual Strides for CJD run/walk have been applied to research grants awarded since 2016.

The CJD Foundation Grant

Contributed by: The Families of the CJD Foundation

Funds donated by supporters of the CJD Foundation have been applied to research grants awarded since 2009.