# The role of unique adipose tissue macrophage populations in obesity

> **NIH NIH K08** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $153,622

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposed five-year training program will develop my independent research career as an academic pediatric
allergist/immunologist seeking to better understand how obesity and other metabolic derangements influence
atopic disease states such as asthma and food allergy. I have completed an MD and PhD in innate immunology,
pediatrics residency training, and am entering my final year of fellowship training in allergy and immunology at
the Children’s Hospital of Philadelphia (CHOP). My immediate goal is to refine the essential skills necessary for
a successful career as an independent investigator. Specifically, I want to be immersed in the field of metabolism,
and gain new expertise with advanced and unbiased transcriptomic techniques to complement my prior training
in experimental and clinical immunology. My mentor for this award is Dr. Mitchell Lazar, an eminent physician-
scientist and expert in the fields of metabolism and epigenetics. To add depth and breadth to my scientific and
career guidance, I am supported by an advisory committee composed of scientists and physician-scientists from
relevant and complementary fields. I have secured the complete support of my institution, and will benefit greatly
from the unparalleled resources and mentorship available at both CHOP and the University of Pennsylvania over
the course of this award.
 My proposal focuses on how adipose tissue macrophages (ATMs) influence adiposity and obesity-related
outcomes. ATMs can protect against or promote obesity depending on context, discordant observations that
raise fundamental questions as to the number and functions of distinct ATM populations. Drawing on the
expertise of the Lazar lab, I utilized single-cell mRNA sequencing and flow cytometry to identify two,
transcriptionally-distinct ATM populations in obese mice and humans. Gene ontology analysis indicated that
these ATM subsets are equipped to have distinct functions: one that is proinflammatory and one that is tissue-
regulatory. These ATM subsets are differentially regulated in an inbred mouse strain that is genetically-resistant
to obesity and an established model of genetic variation in humans, implicating ATM subsets in mediating obesity
susceptibility. Together, these findings have led me to develop the hypothesis that ATMs exist in more than one
functional state, and that differences in the relative proportion of functionally distinct ATMs influence the adipose
tissue environment and susceptibility to obesity. This proposal outlines a series of studies that have the potential
to fundamentally reshape our view of ATM biology, and have implications for the development of personalized
medical approaches for obesity. Importantly, the skills that I gain through the proposed training program will
facilitate my long-term goal of using basic and translational research approaches to understand how obesity and
other metabolic derangements influence atopic disease states, such as asthma a...

## Key facts

- **NIH application ID:** 10146356
- **Project number:** 5K08DK116668-04
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** David Andrew Hill
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $153,622
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146356

## Citation

> US National Institutes of Health, RePORTER application 10146356, The role of unique adipose tissue macrophage populations in obesity (5K08DK116668-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146356. Licensed CC0.

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