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.
Univeristy of Chicago
- Assistant Professor
1990
NIADDK, NIH
- Clinical Staff Fellow
1984
Hospital of the University of Pennsylvania
- Fellowship
1981
Hospital of the University of Pennsylvania
- Residency
1980
Philadelphia Naval Hospital
Philadelphia
- Internship
1976
University of Chicago
- Associate Professor
The renin-angiotensin system mediates EGF receptor-vitamin d receptor cross-talk in colitis-associated colon cancer.
The renin-angiotensin system mediates EGF receptor-vitamin d receptor cross-talk in colitis-associated colon cancer. Clin Cancer Res. 2014 Nov 15; 20(22):5848-5859.
PMID: 25212605
Titanium dioxide in the service of the biomedical revolution.
Titanium dioxide in the service of the biomedical revolution. Chem Rev. 2014 Oct 08; 114(19):10177-216.
PMID: 25171650
Enteric bacterial protein AvrA promotes colonic tumorigenesis and activates colonic beta-catenin signaling pathway.
Enteric bacterial protein AvrA promotes colonic tumorigenesis and activates colonic beta-catenin signaling pathway. Oncogenesis. 2014 Jun 09; 3:e105.
PMID: 24911876
TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-?B suppression.
TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-?B suppression. PLoS One. 2014; 9(5):e97456.
PMID: 24857966
T-oligo as an anticancer agent in colorectal cancer.
T-oligo as an anticancer agent in colorectal cancer. Biochem Biophys Res Commun. 2014 Apr 04; 446(2):596-601.
PMID: 24632202
Is RXRa crucially involved in intestinal inflammation?
Is RXRa crucially involved in intestinal inflammation? Dig Dis Sci. 2014 Apr; 59(4):702-3.
PMID: 24429511
Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis.
Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis. J Clin Invest. 2013 Sep; 123(9):3983-96.
PMID: 23945234
Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.
Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions. Inflamm Bowel Dis. 2013 Mar; 19(3):461-70.
PMID: 23388545
Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions.
Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions. Int J Mol Sci. 2013 Jan 31; 14(2):2980-95.
PMID: 23434653
Evaluation of microvascular density in Barrett's associated neoplasia.
Evaluation of microvascular density in Barrett's associated neoplasia. Mod Pathol. 2013 Jan; 26(1):125-30.
PMID: 22918163