Characterize responses to epithelial injury in esophageal submucosal glands (ESMGs). Using human tissue, characterize changes in sumucosal progenitor niche with and without different types of esophageal injury. Compare changes in progenitor/stem cell marker expression and submucosal myofibroblast injury before and after esophageal injury.
In human esophagus, we have identified ductal metaplasia in esophageal submucosal glands associated with esophageal adenocarcinoma (paper submitted).
Above: Normal ESMG
Below in A and B: ESMG with ductal metaplasia and inflammation
Delineate the causes and consequences of submucosal progenitor niche activation using in vitro systems. Esophageal culture models are used to evaluate potential stem cell niches in the esophagus and growth factors associated with phenotypic outgrowths in culture.
Dr. Garman is a member of The Cancer Genome Atlas Project Stomach/Esophageal working group. Through Duke’s Gastrointestinal Tissue Repository (Garman, PI), Duke contributed patient samples to this working group. Work is progressing on the first esophageal TCGA paper. The first gastric paper has been published. The paper describes four molecular subtypes of gastric cancer: EBV-infected tumors (PIK3CA mutations, CDKN2A silencing, PD-L1/2 overexpression), MSI tumors (hypermutation), genomically stable tumors (diffuse histology, CDH1, RHOA mutations, cell adhesion), and chromosomally unstable tumors (intestinal histology, P53 mutations, RTK-RAS activation).
The paper: http://www.nature.com/nature/journal/v513/n7517/full/nature13480.html
With a medicine resident, Alan Erdman, Dr. Garman and the Duke GI Women’s Group have identified knowledge gaps in ergonomics of endoscopy. We have designed a survey for GI endoscopists. We are working with the AGA Women’s Committee on this project.