The Garman Lab is located in the Carmichael Building at Duke as part of Duke’s Molecular Physiology Institute where we study injury, repair, and the development of cancer in the gastrointestinal tract. We are active members of Duke’s Division of Gastroenterology. In the Garman Lab, we are particularly interested in the upper GI tract, including the esophagus and the stomach.  We study the role of the esophageal submucosal glands as a progenitor cell niche and we are particularly interested in the process of metaplasia in the esophagus and stomach. This includes acinar ductal metaplasia in the esophageal submucosal glands, Barrett’s esophagus,  as well as gastric intestinal metaplasia in the stomach.

Our research includes translational and basic science with a firm foundation in relevant clinical questions. In order to do ensure a strong connection to human health, we have created clinical resources such as the IRB-approved Duke GI tissue repository through which we bank research samples at the time of endoscopy. The GI tissue repository has grown over the past few years and now provides frozen and fresh samples to the Garman Lab as well as to other basic and translational groups. We could not pursue this important research without community and clinical partners and we are grateful for the insights, help, and support they provide.

Esophageal Research: 

In the Garman lab, we begin with observations from human studies and then use models in the lab in order to delve more deeply into the underlying biology. An example of this retro-translational process was a study using our large esophagectomy database to generate new observations about esophageal submucosal glands (ESMGs) (1). We found that while normal ESMGs are made of mucin-filled acini, in other situations (such as when an esophageal cancer is present or when there is an esophageal ulcer) the ESMGs were filled with areas of acinar ductal metaplasia; instead of normal mucin-filled acini, the glands were filled with duct-like structures. These duct-like cells showed markers of proliferation and shared markers with Barrett’s metaplasia. We then developed models of esophageal repair that allowed us to prospectively evaluate the way that the ESMGS respond to injury (2). Again, after injury, the ESMGs became proliferative and assumed a ductal appearance with expression of markers such as SOX9, cytokeratin 7 (KRT7). We also found areas of continuity between the ESMG ducts and areas of new squamous epithelium. One of the most interesting findings of our work thus far is that when we grow ESMGs in 3D culture, two types of spheroids form: one spheroid type is solid and one that is hollow with markers of ducts and Barrett’s esophagus (3).

Using the models that we’ve developed, we are studying how different factors influence the type of spheroids that form from ESMGs in 3D culture. This work is helping us understand more about how Barrett’s metaplasia (a precursor to esophageal adenocarcinoma) forms. Our NIH funding has enabled us to study the role of gastrin in esophageal repair and development of neoplasia (R01-DK118022).

We have written a review focused on the esophageal microbiota and this is a good example of a project driven by a curious medical student (5). Moving forward, we remain focused on esophageal wound healing and the role of inflammation on esophageal progenitor cells in both normal and abnormal wound healing. We are excited to partner with Case Western in this work moving forward.

Gastric Research

The second main focus are for our group is H. pylori infection and gastric inflammation, metaplasia, and gastric cancer. Dr. Garman partners with Dr. Meira Epplein, a cancer epidemiologist at Duke, for this important work. We are interested in improving H. pylori eradication as a means of gastric cancer prevention (4).  Through Duke’s Cancer Disparities NIH-funded P20, as part of the gastric cancer project, we have been investigating H. pylori virulence factors in patients at Duke in order to gain insights into how to address disparities associated with gastric cancer. A major part of our work related to H. pylori, gastric intestinal metaplasia, and gastric cancer centers around creation of gastric organoids, and we are extremely grateful to the patients who partner with us and participate in research. After obtaining informed consent, we are able to use patient-derived samples to generate gastric organoids to study gastric intestinal metaplasia.

Training Environment:

Finally, we aim to provide a supportive and collaborative learning environment in the lab. We welcome medical students, fellows and post-docs who are curious, creative and interested in using scientific discovery to promote health. Dr. Garman is the recipient of mentorship awards and is dedicated to training the next generation of physician scientists.

The Garman Lab has several key collaborators:

• Case Western Reserve University: Amitabh Chak, Kishore Guda, and Andrew Blum
• The Epplein group (Population Health Sciences and Duke Cancer Institute)
• The Newgard Lab for viral vectors used in 3D culture
• The Gregory Lab and the Molecular Genomics Core
• The Blikslager Lab and the Gonzalez Lab at NC State and UNC’s Center for GI Biology and Disease (CGIBD) Large Animal Core
• Dr. Shannon McCall and Duke’s BioRepository & Precision Pathology Center (BRCP) as well as the Research Immunohistology Lab.

References:

1. Garman KS, Kruger L, Thomas S, Swiderska-Syn M, Moser BK, Diehl AM, McCall SJ. Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma. Histopathology. 2015. Epub 2015/04/08. doi: 10.1111/his.12707. PubMed PMID: 25847432.
2. Kruger L, Gonzalez LM, Pridgen TA, McCall SJ, von Furstenberg R, Harnden I, Carnighan GE, Cox AM, Blikslager AT, Garman KS. Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair. Am J Physiol Gastrointest Liver Physiol. 2017:ajpgi 00036 2017. doi: 10.1152/ajpgi.00036.2017. PubMed PMID: 28572084.
3. von Furstenberg R, Li J, Stolarchuk C, Feder R, Campbell A, Kruger L, Gonzalez LM, Blikslager A, Cardona DM, McCall SJ, Henning SJ, Garman KS. Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation. Cellular and Molecular Gastroenterology and Hepatology. 2017;in press. Epub Aug 04, 2017. doi: http://dx.doi.org/10.1016/j.jcmgh.2017.07.005. PubMed PMID: 28936470; PMCID: PMC5602779.
4. Feder R, Posner S, Qin Y, Zheng J, Chow SC, Garman KS. Helicobacter pylori-associated peptic ulcer disease: A retrospective analysis of post-treatment testing practices. Helicobacter. 2018;23(6):e12540. Epub 2018/09/25. doi: 10.1111/hel.12540. PubMed PMID: 30246287.
5. Ajayi TA, Cantrell S, Spann A, Garman KS. Barrett’s esophagus and esophageal cancer: Links to microbes and the microbiome. PLoS Pathog. 2018;14(12):e1007384. Epub 2018/12/21. doi: 10.1371/journal.ppat.1007384. PubMed PMID: 30571768; PMCID: PMC6301555.