Northwestern University Feinberg School of Medicine
Disordered Tissue Biomechanics as a Driver of Esophageal Disease
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Project 1: Ex-Vivo

To determine the molecular mechanisms that alter esophageal distensibility of the esophageal wall

PIs: Marie-Pier Tetreaultm PhD; Peter Kharilas, MD

Co-Investigators: Nirmala Gonsalves, MD (GI), Guang Yu Yang, PhD (Pathology), Scott Budinger, MD (Pulmonary/Critical Care), Seema Aceves, MD, PhD (UCSD)

Specific Aims

Aim 1: To investigate epithelial IKKβ/NFkB and STAT3 signaling as modulators of altered esophageal luminal distensibility measured using FLIP topography and 4-D impedance manometry (4D-IM) in subjects with EoE, SSc, and achalasia.

Aim 2: To determine the role of epithelial IKKβ signaling in promoting fibrosis in EoE.

Aim 3: To determine the requirement for epithelial STAT3 signaling in promoting esophageal smooth muscle cell loss in scleroderma esophageal disease.

Central Hypotheses

  • Esophageal bolus transport is impaired in EoE, SSc, and achalasia.
  • However, the molecular mechanisms leading to these structural aberrations are not understood.
  • We hypothesize that altered esophageal distensibility is mediated through differential IKKβ activation in the esophageal mucosa triggered by either eosinophilic inflammation in EoE or abnormal luminal pressurization in achalasia and that STAT3 signaling promotes esophageal smooth muscle atrophy in SSc.