Descriptions and progress of each award can be found in the project details.
Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty click on their names below.
Unraveling the amyloid fibril with polyphenols
Principal Investigator: Jin-Moo Lee (WashU Neurology)
Co-investigators: Carl Frieden (WashU Biochemistry), John Heuser (WashU Cell Biology & Physiology), Rohit Pappu (WashU Biomedical Engineering), David Wozniak (WashU Psychiatry)
Polyphenols are natural substances found in vegetables, fruits, roots, flowers, tea, and wine. These micronutrients have antioxidant properties and may play a role in disease prevention. This project will discover whether specific polyphenols can reverse the pathological aggregation of amyloid protein and amyloid plaques of Alzheimer’s Disease. This project brings together accomplished investigators from five departments, with a remarkable range of experimental techniques from high resolution atomic force microscopy to mouse behavior.
Grants and Awards
“Untangling Amyloid Plaques with Proteases”
NIH/NINDS R01 NS067905-01 (PI, Lee)
The aim of this project is to investigate the Aβ-degrading and amyloid fibril-degrading activity of MMP-9 in an animal model of Alzheimer’s disease to determine its role in plaque pathogenesis.
Zhang R, Hu X, Khant H, Ludtke SJ, Chiu W, Schmid MF, Frieden C, Lee JM. Inter-protofilament interactions between Alzheimer’s Abeta1-42 peptides in amyloid fibrils revealed by cryoEM. PNAS (2009).
Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. PNAS (2009).
Yan P., Bero A., Cirrito J.R., Xiao Q., Hu X., Wang Y., Gonzales E., Holtzman D.M., Lee J.-M., Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice. J Neurosci (2009).
Hu S., Yan P., Maslov K., Lee J.-M., Wang L.V. Intravital imaging of amyloid plaques in a transgenic mouse model using optical-resolution photacoustic microscopy. Optic Letters (2009).
Updated June 2017
In vivo labeled proteomics in human CSF
Principal Investigator: Randall Bateman (WashU Neurology)
Co-investigators: Donald Elbert (formerly WashU Biomedical Engineering), Alison Goate (formerly WashU Psychiatry)
Dr. Randy Bateman is a new faculty member of the Hope Center. A neurology physician-scientist working in Dr. David Holtzman’s laboratory, Dr. Bateman developed a new method for measuring the production of brain proteins by sensitive measurement from human cerebrospinal fluid. This technique has been used for pioneering studies of Alzheimer’s Disease and now offers potential for use in early diagnosis and treatment of a range of important neurological conditions.
Grants and Awards
FACS study was awarded a supplemental grant from Specific Aim 1
Elbert DL, Mawuenyega KG, Scott EA, Wildsmith KR, Bateman RJ. Stable isotope labeling tandem mass spectrometry (SILT): integration with peptide identification and extension to data-dependent scans. J Proteome Res (2008).
Updated January 2019
Use of hybrid mammalian-yeast prions to identify factors that inhibit protein aggregation
Principal Investigator: David Harris (formerly WashU Cell Biology & Physiology)
Co-investigator: Heather True (WashU Cell Biology & Physiology)
Prion proteins are involved in fatal neurodegenerative brain illnesses including Jacob-Creutzfeld Disease and “Mad Cow” disease. These diseases are like other neurodegenerative diseases in that the primary pathology starts with abnormal accumulation of proteins within brain cells. This project is a collaboration between two Hope Center faculty members: David Harris is an established prion neuroscientis; Heather True is a yeast cell biologist. Together, they have developed an innovative technique which uses yeast to screen many thousands of genes at a time, to find those genes which potentially inhibit protein misfolding and aggregation.
Tank EM, Harris DA, Desai AA, True HL. Prion protein repeat expansion results in increased aggregation and reveals phenotypic variability. Molecular Cell Biology (2007).
Kalastavadi T, True HL. Prion protein insertional mutations increase aggregation propensity but not fiber stability. BMC Biochemistry (2008).
Updated June 2017