Project Grant R21AG085586
- This Project Grant award from the National Institute on Aging's Aging Research program (CFDA 93.866) provides $2,181,250 in funding to the Seattle Institute For Biomedical And Clinical Research to develop small molecule inhibitors of the MSUT2 protein as a potential therapeutic approach for treating tauopathy disorders such as frontotemporal lobar degeneration, Alzheimer's disease, and related conditions. The project aims to optimize potent and brain-penetrant MSUT2 inhibitors and demonstrate...
- Summary The National Institute on Aging awarded Weill Medical College of Cornell University a $717,709 Project Grant, effective June 1, 2025 through March 31, 2030, under the Aging Research program (CFDA 93.866) to conduct research investigating proteomic changes associated with tauopathy in human neurons. The research will employ advanced proteogenomic approaches, including Ascorbic Acid Peroxidase (APEX) proximity labeling, Affinity Purification Mass Spectrometry (AP-MS), and transcriptomics...
- This $1,823,353 Project Grant awarded by the National Institute on Aging (CFDA 93.866 Aging Research) to the Seattle Institute For Biomedical And Clinical Research aims to elucidate the molecular mechanisms by which pathological tau protein causes neurodegeneration in Alzheimer's disease (AD) and related tauopathy disorders. The research project will leverage a C. elegans model of tauopathy to investigate the functional role of nuclear speckles, membraneless organelles involved in RNA...
- This federal Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) will support research at Virginia Commonwealth University (VCU) to investigate the effect of the trans-synaptic spread of pathogenic tau protein in the hippocampus and its impact on vulnerable neuron subtypes in Alzheimer's disease (AD). The $408,638 award, effective from August 1, 2024 to July 31, 2026, will involve the use of adeno-associated viral vector transfection, immunofluorescence, and...
- This Project Grant award from the National Institutes of Health's Aging Research program (CFDA 93.866) will support research to identify early transcriptional and pathological changes in brain regions vulnerable to Alzheimer's disease (AD). The $459,076 award, granted to Trustees of Boston University, will use single-nucleus RNA sequencing and targeted mass spectrometry to profile cell type-specific gene expression and tau/amyloid beta proteoforms in the transentorhinal cortex, entorhinal...
- This Project Grant award of $328,000 from the National Institute on Aging (CFDA 93.866 - Aging Research) supports the Alzheimer's Disease Organelle Proteome Task (ADOPT) pilot phase. The interdisciplinary research team, led by Drs. Biao Wang and Danielle Swaney at the University of California, San Francisco, will use a genetic organelle tagging approach to rapidly purify lysosomes from neurons in wild-type and Alzheimer's disease mouse models. A suite of mass spectrometry experiments will then...
- This Project Grant award, with a total funding amount of $431,750, was provided by the National Institute on Aging (NIA) under the Aging Research federal grant program (CFDA 93.866). The award is for the development and evaluation of a novel immuno-gene therapy approach using a single-chain fragment variable (scFv) derived from an anti-tau oligomeric complex 1 (TOC1) antibody. The key objectives are to: 1) generate and validate the TOC1-scFv-HaloTag-Proteasome Degradation Signal (PDS)...
- This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) aims to investigate how aging produces ultrastructural alterations to neuronal autophagy, which is critical for maintaining neuronal homeostasis and function. The $429,000 award to the University of Texas Health Science Center at Houston will be used to accomplish two specific aims over the 2-year project period starting January 1, 2025: Compare the ultrastructural features of axonal autophagic...
- This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) totaling $433,125 will fund a study to investigate the relationship between microglia, neurons, and tau pathology in Alzheimer's disease. The research will utilize a novel model system of microglial co-cultures with hippocampal assembloids derived from patient-derived induced pluripotent stem cell (iPSC) lines with MAPT mutations and healthy controls. The goal is to explore how bidirectional changes...
- This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) aims to gain a mechanistic understanding of the role of cellular senescence in the pathogenesis of Alzheimer's disease (AD). The $460,625 grant will fund research at the University of Massachusetts Medical School to dissect the separate P53/P21 and P16 senescence pathways and their functional consequences in AD using human induced pluripotent stem cell-based models. The 2-year project will produce...
TARGETING AGE-RELATED ENDOSOME DYSFUNCTION TO TREAT COGNITIVE DECLINE AND ALZHEIMER'S DISEASE - ALZHEIMER'S DISEASE (AD) IS A PROGRESSIVE NEURODEGENERATIVE DISEASE WITH A GROWING HUMANITARIAN AND ECONOMIC BURDEN. ADVANCED AGE IS THE GREATEST RISK FACTOR FOR AD SO THE LONG- TERM GOAL OF THIS RESEARCH IS TO BETTER UNDERSTAND HOW ADVANCING AGE CONTRIBUTES TO AD OCCURRENCE AND PROGRESSION. AGING AND AD PATHOLOGY ARE CHARACTERIZED BY A DECLINE IN THE CELL'S ABILITY TO ELIMINATE DAMAGED AND PATHOLOGICAL PROTEINS THROUGH ENDOSOME TRAFFICKING (NOT- 21-034) WHICH CONTRIBUTES TO THE ACCUMULATION OF PROTEIN LIKE TAU WITHIN NEURONS AND OTHER CELLS OF THE BRAIN. WE HAVE IDENTIFIED A KEY PROTEIN INVOLVED IN THE FORMATION OF ENDOSOMES, THE VEHICLE FOR ENDOSOME TRAFFICKING, THAT IS DECREASED IN NEURONS ACROSS THE LIFESPAN AND FURTHER DECREASED IN NEURONS FROM DONORS WITH AD. WE HAVE SHOWN THAT WE CAN RESTORE EXPRESSION OF THIS PROTEIN IN PATIENT-DERIVED HUMAN NEURONS USING ADENO-ASSOCIATED VIRUS (AAV) AND THAT THIS DECREASES INTRACELLULAR TAU. BASED ON THESE FINDINGS, THE SPECIFIC AIMS OF THIS PROPOSAL ARE TO: 1) DETERMINE HOW INCREASING ENDOSOME FORMATION DECREASES TAU IN NEURONS AND 2) DEFINE HOW INCREASING ENDOSOME FORMATION INFLUENCES COGNITION AND AD PATHOLOGY IN TRANSGENIC AND AGED WILD TYPE MICE. IF SUCCESSFUL, THESE STUDIES WILL ESTABLISH DECREASED ENDOSOME FORMATION AS A CAUSE OF TAU PATHOLOGY IN AD AND SUPPORT THE DEVELOPMENT OF THERAPEUTIC STRATEGIES TO ENHANCE ENDOSOME FORMATION FOR THE TREATMENT OF AD AND OTHER PROTEINOPATHIES (I.E., FRONTOTEMPORAL DEMENTIA, PARKINSON'S DISEASE AND OTHERS).
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $19.2k | 4/28/25 | ||
| Not listed | $172.7k | 3/21/25 | ||
| Not listed | $172.7k | 3/21/25 | ||
| Not listed | $230.3k | 7/2/24 | ||
| Not listed | $230.3k | 7/2/24 |