# Endocannabinoid Biosynthesis in Inflammation and Pain

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $9,863

## Abstract

Globally, chronic disorders including cardiovascular disease, diabetes, cancer, and chronic
respiratory disorders represent one of the largest causes of death in industrialized societies. Besides life-
threatening disease, chronic pain currently inflicts millions of American adults and contributes to billions ever
year in medical costs. While complex molecular factors underlie these heterogeneous pathologies, a
unifying feature of numerous chronic disorders is non-resolved inflammation. Thus, new anti-inflammatory
targets are needed to combat the burden of chronic inflammatory disease.
 Macrophages accumulate at inflammatory sites to produce lipid and protein inflammatory signaling
molecules that can cause profound changes in physiology including sensitization of peripheral sensory
neurons to promote pathogenesis of chronic pain. We previously discovered that diacylglycerol lipase-beta
(DAGLB) regulates an endocannabinoid-eicosanoid lipid-signaling network critical for activation of
proinflammatory responses in macrophages. Recent preliminary data further support DAGLB-regulated lipid
pathways as a safe and effective point of intervention in mouse models of inflammatory and neuropathic
pain that lack gastrointestinal and overt behavioral side effects. Our proposed studies build on published
data from our group as well as others that point to DAGLB-regulated pathways in macrophages as a novel
anti-inflammatory target for treating chronic inflammation and pain.
 Sage Cho will be actively involved in analyzing gene expression changes in macrophages where
diacylglycerol lipase-beta (DAGLB) has been genetically disrupted in primary bone marrow-derived
macrophages (BMDMs). We hypothesize that DAGLB disruption results in alterations in metabolic and signaling
programs in BMDMs that result in global reprogramming of macrophage biology. Sage will be actively involved
in using computational tools to determine gene expression changes that are statistically significant in DAGLB
wild-type (WT) and knockout (KO) BMDMs from recent RNA-seq analyses in our group. The expected outcomes
are identification of network wide changes in kinase and other signaling networks that are regulated by DAGLB.
The impact of the NIDA Summer Research Internship Program is 1) trainee will receive important training on
endocannabinoid lipid signaling and computational approaches for global transcriptomics, and 2) identification
of biomarkers of DAGLB activity, which is important for translating this target for development of non-opioid
analgesics.

## Key facts

- **NIH application ID:** 10400420
- **Project number:** 3R01DA043571-04S2
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Ku-Lung Hsu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,863
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400420

## Citation

> US National Institutes of Health, RePORTER application 10400420, Endocannabinoid Biosynthesis in Inflammation and Pain (3R01DA043571-04S2). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10400420. Licensed CC0.

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