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Leonardo Cortez, PhD & Valerie Sim, MD, FRCPC

Grant Title: Prion protein aggregate size distribution drives clinical phenotype

Location: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

Grant Year: 2022

CJD patients have a wide range of symptoms and disease durations, even though all are caused by the same prion protein, PrP. How is this possible? We know that PrP can misfold into many shapes and clump into many sizes. We propose that the relative sizes of particles in specific brain regions determines what symptoms a patient develops and how quickly they succumb. We will measure prion sizes from different brain regions of patients who had different symptoms and disease durations, to see which sizes correlate with which symptoms. We will also assess whether different membrane environments in different brain regions might be responsible for the different PrP sizes, since we know that prion misfolding occurs on the membrane and is affected by membrane changes.

About the Researchers:

Leonardo Cortez, PhD
Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

Dr Leonardo Cortez is a Research Associate in the laboratory of Dr. Valerie Sim, at the Centre for Prions and Protein Folding Diseases, University of Alberta, Canada. He attained his B.Sc and PhD in Biological Chemistry at the University of Buenos Aires, Argentina, followed by post-doctoral training at the University of Alberta, Canada. He has worked in the Sim laboratory since 2011, where he has been studying the biophysical properties and biochemical mechanisms of aggregation-prone proteins, including prion protein and amyloid beta, and how they relate to neurodegenerative disease pathologies. He has published studies on how molecular changes in prion protein sequence affect aggregation, how anti-prion compounds may interfere with prion disease pathogenesis, and how prion aggregate size correlates with clinical phenotype. He is currently isolating and characterizing human brain-derived prion particles to better understand how the biophysics of a prion aggregate may drive the heterogeneous presentation of prion disease in patients.

Valerie Sim, MD, FRCPC
Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada

Dr. Valerie Sim is a prion scientist at the Centre for Prions and Protein Folding Diseases at the University of Alberta, and a clinical neurologist at the University of Alberta Hospital, in Edmonton, AB, Canada. She is the medical director of the Canadian CJD Association and co-founder of the Edmonton Cognitive Neurology Clinic.

After her obtaining her BSc(Hon) and MD at the University of Calgary, followed by a neurology residency at the University of Ottawa, Dr. Sim completed a post-doctoral fellowship in prion disease research at Rocky Mountain Laboratories, NIH, Montana, under the supervision of Dr. Byron Caughey. She joined the University of Alberta Division of Neurology in 2009 and was promoted to associate professor with tenure in July 2016.

In her research lab, Dr Sim is interested in understanding how a prion’s size and shape can influence patterns of disease and risks of transmission. She isolates prion particles from infected brain samples using asymmetric flow field-flow fractionation and examines pathogenesis in a “prion-disease-in-a-dish” brain slice culture model. From light scattering analysis and protein biochemistry to animal treatment experiments, her research publications have received international media attention.

She is also passionate about promoting science communication and has published a TEDx talk on prion disease. She regularly presents the science of prion disease to diverse communities across Alberta, Canada, and internationally.

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.