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overview Brief Summary of Clinical activities: General gastroenterology. Diagnosis, management, and where appropriate, triage of patients with gastrointestinal disorders, including abdominal pain, GI bleeding, iron deficiency anemia, diarrhea, constipation, malabsorption, weight loss, GERD (esophageal reflux), swallowing difficulties, esophageal strictures, peptic ulcer disease, Barrett’s esophagus, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colon polyps and colon cancer, diverticulitis, gastritis, H pylori infections, angioectasias (AVMs), radiation proctitis, pancreatitis and liver abnormalities. Brief Summary of Research activities: 1. Colon cancer pathogenesis and chemoprevention – Our laboratory is focused on the role of diet and signaling pathways that promote or inhibit colon cancer development. These include tumor-promoting Western diets, and inhibitory fish oil diets, growth factor signals and cytokine signals, focusing on ADAM17-EGFR and CXCL12-CXCR4. For these studies, we use animal models, primary human tissue and colonic organoids, and in vitro cell culture models. We are currently carrying out a broad screen of natural products for compounds that inhibit CXCL12-CXCR4 interaction as potential chemopreventive agents for colon cancer. 2. Development of a liquid biopsy (blood test) for colon cancer screening. In collaboration with Dr. Chuan He at the University of Chicago and Dr. Wei Zhang at Northwestern University, we are developing biomarker assays in the blood using 5-hydroxymethylcytosine to diagnose patients with advanced adenomas and early CRC. Similar assays will be used to prognosticate the likelihood of tumor recurrence and assess responses to anti-tumor therapies. 3. Elucidation of the role of Ythdf1 in colon cancer development. Ythdf1 binds N6-methyadenosine (m6A) in mRNA to increase mRNA translation We showed that deletion of Ythdf1 in dendritic cells activated the antigen-specific CD8+ T cell anti-tumor response allowing recognition and killing of colon cancer cells. We are currently studying conditional (LoxP) compound mutant mice with LoxP Ythdf1 and LoxP Apc genes to uncover the role of this m6A mRNA reader in early colonic carcinogenesis. 4. Dissection of the role of the pro-renin receptor (Atp6ap2) in colon cancer. In prior studies we showed that inhibition of the renin-angiotensin system (RAS) is essential for the chemopreventive efficacy of vitamin D to suppress colon tumor development. Vitamin D suppresses renin transcription to reduce RAS signals. AT1 receptor blockade by losartan also suppresses tumor development. The (pro)renin receptor binds renin and catalyzes renin protease activity and induces Wnt signaling. In collaboration with Dr. Yan Chun Li, we are investigating colonic tumorigenesis in mice with conditional deletion of (pro)renin receptor. This deletion (and wild type controls) will be combined with mice expressing a transgene driving renin over-expression.

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