# Exchange Protein directly Activated by cAMP (EPAC): Structure, Function and  Therapeutics

> **NIH NIH R35** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $47,999

## Abstract

PROJECT SUMMARY
This is an equipment supplement request in response to NOT-GM-20-013 for a parental project
R35GM0122536, which focuses on studying the pleiotropic second messenger cyclic AMP (cAMP) system.
cAMP is a major stress signal that regulates a myriad of important biological processes under both
physiological and pathological conditions, including cancer, chronic pain, diabetes, heart failure, and
infections. Hence, not surprisingly, the cAMP signaling cascade is one of the most targeted pathways by current
pharmaceuticals. In multi-cellular eukaryotic organisms, the effects of cAMP are mainly transduced by two
ubiquitously-expressed intracellular cAMP receptors, the classic protein kinase A/cAMP-dependent protein
kinase (PKA/cAPK) and the more recently discovered exchange proteins directly activated by cAMP/cAMP-
regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF). While accumulating evidence implicates
EPAC proteins as important stress response switches in the development of various human diseases, major
gaps in our basic understanding of EPAC structures and functions persist. To bridge these gaps, we will apply
structural, pharmacological and genetic approaches to interrogate the mechanisms of action and biological
functions of this important family of signaling molecules, leading to the assessment of EPAC proteins as
potential therapeutic targets in various disease models. The proposed research is based on more than
seventeen years of extensive fundamental studies of EPAC-mediated signaling and directly builds on several
recent developments in our laboratory, which include the characterization of EPAC knockout mice and the
discovery of first-in-class EPAC specific inhibitors. The combination of complementary structural approaches,
novel genetic animal models and pharmacological probes will enable us to reveal much desired mechanistic
insight and in vivo functions of EPAC proteins. This research plan will also aid in the advancement of new
pharmacological tools for deciphering EPAC-mediated cell signaling and disease mechanisms, which can pave
the way for novel, mechanism-based therapeutic strategies specifically targeting cAMP/EPAC signaling.

## Key facts

- **NIH application ID:** 10133377
- **Project number:** 3R35GM122536-03S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** XIAODONG CHENG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $47,999
- **Award type:** 3
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133377

## Citation

> US National Institutes of Health, RePORTER application 10133377, Exchange Protein directly Activated by cAMP (EPAC): Structure, Function and  Therapeutics (3R35GM122536-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133377. Licensed CC0.

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