# Harnessing Single Cell Epigenome-wide profiling of Myeloid cells to Compare and Contrast Alzheimer's from HIV-Associated Cognitive Dysfunction

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $99,012

## Abstract

PROJECT SUMMARY/ ABSTRACT (for Nicholas Hampilos (Ndhlovu): R01 AG063846-01A1
 Supplement Application)
In this application, we seek a diversity research supplement to the parent award “HARNESSING
CELL
ALZHEIMER'S
SINGLE
EPIGENOME-WIDE PROFILING OF MYELOID CELLS TO COMPARE AND CONTRAST
FROM HIV-ASSOCIATED COGNITIVE DYSFUNCTION” (AG063846). The parent award
seeks to define the epigenomic landscape of myeloid populations in order to differentiate HIV Associated
Neurocognitive Disease (HAND) from Mild Cognitive Impairment state of Alzheimer's Disease (MCI-AD) in
individuals living with HIV on suppressive antiretroviral therapy (ART). This diversity supplement will expand
the scope of research in Specific Aim 2 by enabling the addition of cellular immunophenotyping and MRI and
proton magnetic resonance spectroscopy (1H MRS) imaging in 5 subjects with HAND and 5 cognitively normal
subjects with HIV from the parent study, with plans to include subjects with MCI-AD in the future if additional
funding is secured. The main aims of the supplemental research project are 1) to investigate the
neurobiochemical features that may distinguish people living with HIV (PLWH) with HAND versus those without
HAND by measuring neurometabolites in the basal ganglia with 1H MRS and 2) to explore possible
relationships between neurometabolite levels and monocyte counts and phenotypes by linear regression. With
respect to the first aim, our hypothesis is that PLWH with HAND will have lower levels of both GSH and NAA in
the basal ganglia compared to PWLH without HAND, reflecting oxidative stress and greater neuronal injury,
respectively. We also hypothesize that total and intermediate type monocyte counts as well as CCR2 and
CD163 surface expression levels will be inversely correlated with GSH and NAA levels in PLWH, which would
further support monocytes being drivers of neuropathology in PLWH. In addition to funding a supplemental
research project, the NIA diversity supplement would provide a plethora of mentoring, training, and educational
opportunities to Dr. Hampilos at a critical point in his career. More specifically, the diversity supplement would
enable Dr. Hampilos to: 1) gain clinical and laboratory research experience in geriatric Neuro HIV and cellular
immunology through mentoring, coursework and “hands-on” training in immunophenotyping of peripheral
monocytes, which will be required for the proposed supplemental research project, 2) reinforce his radiology
training, by enabling Dr. Hampilos to analyze and interpret MRI and 1H MRS results, 3) provide opportunities to
enhance his presentation, writing skills, and grantsmanship and 4) generate key preliminary data which would
be used to apply for an NIA K22 Career Transition Award and an award from a private foundation in 2024
and/or 2025.

## Key facts

- **NIH application ID:** 11010072
- **Project number:** 3R01AG063846-05S2
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Lishomwa C Ndhlovu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $99,012
- **Award type:** 3
- **Project period:** 2020-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11010072

## Citation

> US National Institutes of Health, RePORTER application 11010072, Harnessing Single Cell Epigenome-wide profiling of Myeloid cells to Compare and Contrast Alzheimer's from HIV-Associated Cognitive Dysfunction (3R01AG063846-05S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11010072. Licensed CC0.

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