# Immune Activation, Cerebral Metabolic Activity and Depression in Treated HIV-Infection

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $185,220

## Abstract

Project Summary
 Depression is a critical medical challenge affecting the morbidity of millions of people living with
HIV despite availability of effective antiretroviral therapy (ART). Subsets of patients with depressive
disorders do not respond to traditional antidepressant treatments, potentially reflecting disease
mechanisms not addressed with standard therapy. This multidisciplinary proposal seeks to understand
the interactions between host factors and neurological function by identifying metabolic pathways
altered in depression using novel high-throughput metabolite profiling coupled with neuroimaging and
immunological studies.
 This K23 Mentored Clinical Scientist Research Career Development Award details a
comprehensive five-year program for the candidate to acquire formal training and mentorship with
specific expertise in advanced computational modeling, and immunity and host defense. In this K23
proposal, the candidate will carry out a neurological substudy within the framework of a randomized,
double-blind, placebo controlled trial in participants with HIV infection. First, the candidate aims to study
cerebral function by positron emission tomography (PET) imaging with 2- [18F]-fluorodeoxyglucose
(FDG), a sensitive indicator of neural activity and will define relationships with immune cell markers and
depression. Second, the candidate seeks to determine the influence of monocyte subsets and
activated T-lymphocytes on depression in treated chronic HIV-infection. Third, by studying the blood
metabolome from HIV-infected individuals with depression in cross-sectional analysis and validating
findings in an independent longitudinal cohort, the candidate will learn how systemic byproducts of
metabolic pathways may be used to identify people living with HIV who are “at risk” for persistent
depressive symptoms.
 During the course of the award, the candidate will explore systemic metabolic pathways
influencing depression in HIV-infected adults on ART with the goal of identifying potential novel
diagnostic and therapeutic targets. The candidate is a board-certified neurologist with prior doctoral
training in molecular biology and neuroscience. In preparation for an independent research career, the
candidate will complete training in bioinformatics for analyzing large-scale datasets, and immunology
through coursework and analysis of clinical, biological and metabolite data derived from the
neurological substudy and multiple existing cohorts with chronic HIV infection. The candidate’s training
will be guided by established mentors in the field of HIV infection and an advisory committee of senior
scientists with collective expertise in HIV-associated neuropathogenesis and metabolic disease,
metabolomics, computational modeling, bioinformatics, biostatistics, and neuroimaging.

## Key facts

- **NIH application ID:** 10105366
- **Project number:** 5K23MH115812-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shibani Sharon Mukerji
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $185,220
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105366

## Citation

> US National Institutes of Health, RePORTER application 10105366, Immune Activation, Cerebral Metabolic Activity and Depression in Treated HIV-Infection (5K23MH115812-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10105366. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*