Jun Sun, Ph.D.

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Research Summary in Sun Lab

The research projects in Dr. Sun's laboratory are focused on the following areas:

1. The link between inflammatory bowel disease and colorectal carcinogenesis

Many common cancers develop as a consequence of chronic inflammation. Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC). The presence of bacteria in the gut appears to be of crucial importance in the pathogenesis of IBD. However, whether bacteria can induce inflammation that results in tumorigenesis or directly causes CRC in humans, analogous to H. pylori causing gastric cancer, is not known. The nature and regulation of the host-bacterial interactions in the gut is thus an area of intense scientific and clinical interest. A better understanding of the role of bacteria in inflammation and cancer will lead to highly targeted strategies in which specific pathways of mammalian cells are selectively affected. We have reported that bacterial activation of beta-catenin signaling, a key player in colonic tumorigenesis in human epithelia. We will determine whether certain bacterial colonization promotes tumorigenesis in the azoxymethane mouse model of colon cancer. In addition, we will investigate the physiological relevance of bacterial effector expression and beta-catenin/NF-kappaB pathway in human specimens of IBD and colon cancer. Our long-range goal is to elucidate how a specific bacterial effector provides a mechanistic link between inflammation of the intestine and the development of colon cancer.

2. The role of bacterial effector AvrA in inhibiting inflammation

AvrA is a pathogenic gene of certain bacteria whose encoded protein is transferred into intestinal epithelial cells through a Type III secretory pathway. In previous studies, we demonstrated that AvrA stabilizes beta-catenin, which is a negative regulator of the proinflammatory NF-kappaB pathway in epithelial cells. We hypothesize that the bacterial effector AvrA inhibits the NF-kappaB pathway and activates the beta-catenin pathway to inhibit intestinal inflammation. Current efforts are to understand the mechanism and effects of AvrA using both in vitro and in vivo approaches. These resulting data will provide important insights into how AvrA contributes to the overall disease-causing properties of pathogenic as well as commensal bacteria, and they have direct relevance to a better understanding of diseases such as inflammatory bowel diseases and infectious colitis.

3. Characterization of expression and function of vitamin D receptor in inflammatory bowel diseases

Vitamin D receptor (VDR) has evolved the ability to protect the body against inflammation in addition to binding vitamin D and regulating calcium homeostasis. The VDR gene is a strong candidate susceptibility gene for IBD. While insights have been gained into immune cells, very little research has been done to assess the effects of the VDR signaling pathway in intestinal mucosa in IBD models. Enteric bacteria play a crucial role in the pathogenesis of IBD. However, bacterial modulation of VDR signaling in colitis remains virtually unexplored. Therefore, we are investigating how bacteria modulate the VDR signaling and how VDR determines the inflammatory response in a colitis model. Given the crucial role of bacteria in the pathogenesis of IBD and the therapeutic and pharmacologic potential of vitamin D in the treatment of IBD, understanding how bacteria regulate the VDR pathway will facilitate the development of targeted interventions to control inflammation.

Current Appointments

• Assistant Professor - Department of Medicine (SMD)
• Assistant Professor - Department of Microbiology and Immunology (SMD)

Lab Description

Our research interests are the microbial-host interaction under normal and inflammatory states. Our projects are supported by the NIH and the American Cancer Society to study IBD and colon cancer.