# Role of mTOR in inflammatory monocytes in HIV infection

> **NIH NIH F30** · NORTHWESTERN UNIVERSITY · 2020 · $50,520

## Abstract

Project Summary
This fellowship training program proposes rigorous didactics, innovative research, and strong inter-disciplinary
collaborations aiding both. It will prepare me for productivity in translational HIV research, as my goal is an
academic career as a physician-scientist advancing elimination of non-AIDS complications of ART-treated HIV
infection. The research proposal builds on my sponsor's recent work on T cell metabolic reprogramming and
HIV replication, extending it to monocyte-related immunopathogenesis of cardiovascular disease in HIV
infected patients. My preliminary data indicate that a catalytic mTOR inhibitor (mTORi), as well as a statin,
diminish ex vivo activation of downstream effectors of mTOR in monocytes from uninfected persons, and
suppress emergence of inflammatory monocyte phenotypes after TLR engagement. A more complete
characterization of the mTOR signaling pathway and its downstream functions in monocytes is proposed to
rigorously delineate its contribution to ongoing inflammation in ART-treated HIV-1 infection. Aim 1 will
determine whether mTOR activity is necessary and sufficient for monocytes to develop an inflammatory
phenotype after exposure ex vivo to LPS (a TLR4 ligand) and RNA (a defined TLR7/8 ligand). I will also
determine whether the inflammatory phenotype of monocytes isolated from HIV-infected donors can be
reversed by ex vivo exposure to mTORi. I also propose to extend my additional preliminary results supporting
the hypothesis that inhibition of mTORC1-dependent cellular functions contributes to the anti-inflammatory
effects of statins. Aim 2 will evaluate the effect of ex vivo statin (rosuvastatin) treatment on mTORC1 and
mTORC2 activity in unstimulated and TLR-stimulated monocytes from uninfected subjects, as well as whether
rosuvastatin blocks a shift to inflammatory CD16+ monocyte phenotypes. I will rigorously study causality using
genetic approaches to impact mTORC1, and also determine whether starting in vivo statin treatment in HIV
patients with recent coronary events is associated with decreasing mTOR activity in their monocytes.

## Key facts

- **NIH application ID:** 9982757
- **Project number:** 5F30AI131937-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Nina Calantone
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-08-17 → 2021-07-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982757

## Citation

> US National Institutes of Health, RePORTER application 9982757, Role of mTOR in inflammatory monocytes in HIV infection (5F30AI131937-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9982757. Licensed CC0.

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