Senior Supervisor N094 & N790
Colorectal cancer, Cancer prevention, Inflammation-driven cancer, Gut microbiota, Intestinal biofilms and IBS, Iron deficiency and thromboembolism
Inflammatory Bowel disease (IBD) is caused by breakdown of intestinal homeostasis in a genetic susceptible host, via a complex interplay of environmental triggers (such as diet, smoking) and interactions between host and gut microbiota.
Persistent mucosal injury and oxidative stress produced by chronic inflammation of gastrointestinal tract in IBD further modulates cellular signaling, leading to genetic instability and neoplasia.
Moreover, disruption of epithelial barrier, dysregulated immune response and microbial dysbiosis alters molecular signaling in the stem cell niche of intestinal crypts.
Anti-inflammatory drug mesalamine (5-ASA) used in the treatment for IBD, also exhibits chemopreventive actions through signaling pathways; such as inhibition of Wnt/β-catenin, PAK1, PI3K/AKT/mTOR and MAP kinase or activation of PPAR-γ and anti-oxidant Nrf2, with pleotropic functions in inflammation and cancer.
Using PAK1KO and intestinal specific PAK1CKO mouse models, we are investigating the role of PAK1 signaling in microbial dysbiosis, intestinal inflammation and cancer.
Microbial dysbiosis contributes to pathophysiology of various conditions and we are examining the association and mechanism of biofilm formation in intestinal diseases; such as IBD, Irritable bowel Syndrome (IBS) and small intestinal bacterial overgrowth (SIBO).
Our research utilizes various mouse models of colorectal cancer and IBD (AOM/DSS, Apcmin, IL-10 KO, Msh2loxP/loxP Villin-Cre), intestinal organoids, human tissue samples, as well as variations in gut microbiota (16S rRNA sequencing, biofilm formation assays), to dissect out the pathomechanisms of intestinal inflammation, cancer and potential chemoprevention.