# The Role of Myeloid Cells in Parkinson's Disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $697,234

## Abstract

Parkinson’s disease (PD) is a progressive, neurodegenerative disorder of aging that 
affects both motor and cognitive function. Despite more than fifty years of research, no cures 
exist and the standard of treatment remains unsatisfactory. Genome-­wide association studies 
(GWAS) have identified many regions harboring variants associated with PD. The next challenge 
in translational research is to identify the causal variants underlying the association signals, 
the affected genes, molecular pathways and their functional consequences. Because genetic 
variants can mediate effects on higher-­order phenotypes through effects on gene 
expression, the integration of transcriptomics into the study of disease associated variants has 
already proven to be a useful strategy, and indeed disease associated loci have been shown 
to be enriched for variants regulating gene expression. We have recently shown that genetic 
variants that affect gene expression in myeloid cells underlie a substantial fraction of the 
genetic associations to PD. We have also accumulated compelling data suggesting that many genes 
involved in autophagy-­lysosomal pathways and mitochondrial function are differentially 
expressed in monocytes and in microglia of PD cases compared to controls and in some cases, are 
genetically regulated by PD-­associated genetic variants. Here, in aim 1, we will generate bulk and 
single cell transcriptome and proteome profiles from 250 peripheral monocytes of early-­stage PD 
(with no medication, within 2 years from the onset of the symptoms), mid-­ to late-­stage 
PD, and age-­matched controls from a well-­characterized PD cohort. The sample collection 
and transcriptome profiles will be done longitudinally (at baseline and follow up within 2 
years). In aim 2, will characterize the transcriptome of primary microglia from 
multiple regions of autopsied brains of PD cases and age-­matched controls and explore the 
consequences on the transcriptome of PD susceptibility variants. We will conduct 
state-­of-­the-­art analyses that will integrate multi-­omic and clinical data sets to generate 
patient derived, data-­driven, multi-­scale models of disease, enabling the generation of 
hypotheses around protein interactions specific to disease states and subgroups. In aim 3, we will 
functionally characterize monocytes and microglia in order to investigate the effects that gene 
expression, protein abundance and network connectivity changes may have on immune functions of 
interest such as: 1) phagocytic capacity;; 2) lysosomal function;; and 3) mitochondrial activity. 
This project will have a large overall impact by: 1) providing key information bridging PD genetics 
to molecular mechanisms in monocytes and microglia, setting the stage for future mechanistic 
studies;; and (2) generating large-­scale, multi-­omic datasets, together with systems level 
analyses of these datasets in innate immune cells, which is an urgently needed resource.

## Key facts

- **NIH application ID:** 10377952
- **Project number:** 5R01NS116006-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Towfique Raj
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $697,234
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377952

## Citation

> US National Institutes of Health, RePORTER application 10377952, The Role of Myeloid Cells in Parkinson's Disease (5R01NS116006-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10377952. Licensed CC0.

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