# Fibrosis of the Lower Esophageal Sphincter in Achalasia

> **NIH NIH K23** · EMORY UNIVERSITY · 2023 · $160,417

## Abstract

Project Summary / Abstract
Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter opening
with swallowing. Achalasia is thought to be caused by ganglion loss in the neural plexus that innervates the
lower esophageal sphincter muscle. Despite excellent approaches to open the lower esophageal sphincter in
achalasia, disease recurrence in achalasia is common. As such, it may be there are additional biomechanical
elements that cause sphincter dysfunction in achalasia. In particular the fibrosis of the lower esophageal
sphincter muscle may play a critical role. This proposal will study the molecular mechanism and physiological
impact of muscle fibrosis in achalasia. Recently, it has been identified that mast cell activation and
degranulation is a prominent feature in achalasia. In this proposal, we will assess the impact of muscle fibrosis
on physiological function of the LES (Aim 1). We will use a novel technology, functional lumen imaging probe
(FLIP) topography, to conduct in vivo experiments and perform ex vivo muscle strip recordings. In Aim 2, we
will assess the mechanism of mast cell activation in causing fibrosis via fibrosis marker expression and cell
culture experiments. This study will facilitate an understanding of the alternative mechanisms of disease
pathogenesis and functional impairment in achalasia. Ultimately this may lead to novel treatment approaches
in achalasia such as molecularly targeted therapy. This study will also provide an in-depth understanding of the
precise components measured by the functional lumen imaging probe. In order to accomplish the aims put
forth in this grant and his career goal as becoming an independent clinical and translational investigator in the
field of esophageal motility disorders, the Principle Investigator, Dr. Anand Jain, will require in-depth training in
both fundamental and advanced biological laboratory techniques used to study smooth muscle, esophageal
functional data analysis, and biostatistics. His career development is enthusiastically supported by his strong
mentorship team, led by R01-funded enteric neuronal biologist Dr. Shanthi Srinivasan at Emory and including
R01-funded esophageal translational esophageal physiologist Dr. Ravinder Mittal from University of California
San Diego. The robust training resources available via the Emory University School of Medicine and protected
time and in kind support provided by the Emory University Department of Medicine and the Division of
Digestive Diseases will facilitate his transformation to an independent clinician scientist.

## Key facts

- **NIH application ID:** 10705229
- **Project number:** 5K23DK131317-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Anand Sagar Jain
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $160,417
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10705229

## Citation

> US National Institutes of Health, RePORTER application 10705229, Fibrosis of the Lower Esophageal Sphincter in Achalasia (5K23DK131317-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10705229. Licensed CC0.

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