# Core E: Mass Spectrometry Core

> **NIH NIH U54** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $293,806

## Abstract

PROJECT SUMMARY/ABSTRACT — MASS SPECTROMETRY CORE
The Mass Spectrometry Core will support research into the causes of tau toxicity in the context of
Frontotemporal Dementia (FTD). The core will apply quantitative proteomics approaches to characterize post-
translational modifications (PTMs) and protein-protein interactions (PPIs) of wildtype and FTD-mutants of tau.
Although tau mutations and dysregulations are prominent in FTD, little is known about tau function in this
disease, which is a common cause of young-onset dementia. A thorough description and exploration of tau-
mediated FTD will provide a significant and essential resource for the neurological disorder community.
We will comprehensively characterize tau PTMs in different cellular compartments and tissues using a novel
platform we have developed that allows for the selective enrichment of tau from human brain tissues and cells.
Combined with quantitative mass spectrometry (MS) approaches, we will comprehensively monitor acetylation,
phosphorylation, ubiquitylation and methylation sites and determine their regulation in the context of FTD
mutations. We will validate FTD mutant regulated PTM sites using a targeted approach called selected reaction
monitoring (SRM). In contrast to systematic PTM site mapping which is used for hypothesis generation, SRM
allows hypothesis testing by quantifying an a priori selected set of PTM sites in a highly accurate, sensitive,
and reproducible fashion across many conditions and larger sample sets.
Additionally, we will generate PPI maps for tau in the context of mutations, perturbations, and different cellular
localizations. We will use classical affinity purification followed by MS (AP-MS) and novel APEX-based
proximity biotinylation to identify tau-interacting proteins mediating aberrant activity and homeostasis in FTD
neurons. We will study the interactome associated with both normal and FTD-mutants of tau in
autophagosomes, autolysosomes and endosomes, and characterize the mechanisms of how tau is released in
an activity-dependent manner as well as study the cellular machinery involved in normal or mutant tau uptake.
The Core will interact with the CRISPR Core to functionally validate proteomics data and with the Data Core to
integrate datasets and share results with the scientific community.

## Key facts

- **NIH application ID:** 10011934
- **Project number:** 5U54NS100717-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Nevan J Krogan
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,806
- **Award type:** 5
- **Project period:** 2016-09-30 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011934

## Citation

> US National Institutes of Health, RePORTER application 10011934, Core E: Mass Spectrometry Core (5U54NS100717-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10011934. Licensed CC0.

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