Cobine Lab

Mission

Advancing the diagnosis, prevention and treatment of esophageal disorders through ground- breaking research on the intricate processes of the lower esophageal sphincter (LES).

Key areas of focus

  • Current emphasis on understanding the mechanisms regulating motility in the gastroesophageal junction (GEJ), a high-pressure zone containing the lower esophageal sphincter (LES).
  • Characterizing the mechanisms controlling motility in the internal anal sphincter (IAS).
  • Improving understanding of the pathophysiology underlying defecatory disorders.
  • Discovering potential targets to treat esophageal disorders.

Lab team

Caroline Cobine, Ph.D., an associate professor in the Department of Physiology and Cell Biology, is dedicated to understanding how the lower esophageal sphincter (LES), functions to prevent esophageal disorders such as Gastroesophageal Reflux Disease (GERD) or achalasia. The Cobine Lab studies the mechanisms regulating motility in the gastroesophageal junction under normal conditions to understand how these regulate the muscle function. Through this research, the lab's goal is to identify novel therapies for preventing and treating esophageal disorders.

  • Caroline Cobine, Ph.D.: Principal Investigator

Notable research findings

  • Demonstrated the dependence of tone in the LES and phasic contractile activity in the distal esophagus on Ca2+ influx and Ca2+-activated Cl- channels (ANO1).
  • Proved that interstitial cells of Cajal (ICC), cells known to generate pacemaker activity in other regions of the gastrointestinal tract, express ANO1 and that two distinct Ca2+ signaling behaviors are present in ICC within the GEJ aligning with differences in contractile behavior between the LES (tonic) and the adjacent distal esophagus (phasic).
  • Discovered that these two distinct Ca2+ signaling behaviors are present in ICC within the IAS, a muscle that exhibits both phasic contractions and tone. In both regions, rhythmic whole-cell Ca2+ transients in ICC and contractile activity are abolished by antagonists of ANO1 and L-type Ca2+ channels suggesting a role for these cells as pacemaker cells.

Equipment, technology and techniques

  • Immunohistochemistry
  • RNAscope in situ hybridization
  • qPCR
  • WES/JESS auto western blotting
  • Spinning-disk confocal microscopy
  • Isometric tension recording

Active grants and research projects

  1. Control of motility in the lower esophageal sphincter.
    • Award: 1R01DK129528
    • Funding organization: National Institute of Health (NIH)