John Sealy

ResearchGastroenterology & Hepatology

Research Activity

The Division of Gastroenterology and Hepatology has undergone tremendous growth and expansion since 1997 with the recruitment of a new Division Director and several other faculty of national and international repute. Consequently, in recent years, we have positioned ourselves as one of the strongest and largest academic GI divisions in the Southwestern United States. Research related to digestive health and disease has been a well-recognized and important strength at UTMB. We have a long history of excellence, as evidenced by faculty members who hold offices in national GI associations, serve on editorial boards of prestigious GI journals, and are members of National Institutes of Health study sections. In addition, the chairs of several UTMB departments are GI or GI-related researchers.

Finally, UTMB consistently ranks in the top 10 of all national and international institutions in the number of presentations at the annual Digestive Diseases Week (the largest GI meeting of the year). A significant portion of NIH dollars at UTMB supports research and training related to digestive diseases. Extramural funding related to research in GI health and disease includes many R01 grants, program project grants and training grants.      

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The Li Laboratory is focused on the etiology, prevention, and therapy of colon cancer, inflammatory bowel diseases (IBD), and extraintestinal manifestations of IBD.

Our team is interested in studying environmental, bacterial, and epigenetic contributions to the development of colorectal cancer, ulcerative colitis, Crohn's disease, and IBD-induced heart diseases, using diverse research tools and techniques that include next-generation sequencing, global proteomics, real-time molecular interactions, and humanized disease models.  These studies have found that early-life inflammation alters gut microbiota and sensitizes the gut epithelium, rendering the host susceptible to an aggravated immune response, a hallmark of IBD, when exposed to an additional inflammation later in life.  We also found that gut microbiota imbalances in IBD epigenetically disrupt the gut/heart cross-talk, resulting in cardiac diseases such as heart failure.  Our mechanistic studies have identified several potential therapeutic targets, including TRAF6, MMP7, and BDNF.  Furthermore, we have developed a number of small molecule inhibitors against these proteins, which are undergoing laboratory and animal testing in various preclinical models of IBD and colorectal cancer.


Mechano-regulation of gene expression in the gut
Mechano-regulation of gene expression in the gut - Dr. X.Z. Peter Shi

Many gastrointestinal disorders are associated with mechanical stretch (distention). Among the stretch-related conditions are bowel obstruction, pseudo-obstruction, achalasia, pyloric stenosis, mega-colon, and constipation. They represent great digestive health challenges in adults and children. Dr. Shi and his colleagues have found that mechanical stretch induces marked expression of mechanically sensitive genes such as COX-2 in the gastrointestinal tract. This novel mechanism of mechanotranscription plays a critical role in the pathophysiology of stretch-related conditions such as bowel obstruction, pseudo-obstruction, achalasia, and constipation. Dr. Shi's lab is awarded by NIH funding to investigate mechano-regulation of gene expression in the gut. A further understanding of the signaling mechanism involved in stretch-induced gene expression in the gut will direct novel treatments towards these disorders.

The secretory function of gut smooth muscle cells
The secretory function of gut smooth muscle cells - Dr. X.Z. Peter Shi

Gut smooth muscle has long been known as a contractile tissue. Recent studies by Dr. Shi and Dr. Sarna demonstrate that gut smooth muscle cell is not just a "passive" contractile cell; it also "actively" participates in the process of inflammation and visceral sensitization by secreting cytokines, chemokines, growth factors and adhesion molecules. Further study on this novel function of gut smooth muscle cell may lead to new therapeutic targets for the treatments of inflammatory bowel disease and irritable bowel syndrome.

This section is currently unavailable. We hope to have it available in the very near future.