Randy C. Mifflin, Ph.D.
Assistant Professor, Division of Gastroenterology and Hepatology
Randy C. Mifflin, Ph.D.
Department of Internal Medicine
University of Texas Medical Branch
301 University Blvd.
Galveston, TX 77555-1064
Dr. Mifflin obtained his Ph.D. in 1988 from the Department of Human Biological Chemistry and Genetics at UTMB. His research over this period involved the study of cell cycle-regulated genes during hepatic regeneration, and hepatic inflammation. In 1991 Dr. Mifflin completed a three year NIH postdoctoral fellowship in the Department of Biochemistry at Baylor College of Medicine. His research over this period focused upon various aspects of mammalian RNA metabolism such as characterization of RNA polymerase II transcription termination and polyadenylation signals using in vitro and in vivo systems. In 1992, Dr. Mifflin returned to UTMB where he became Managing Director of the UTMB Molecular Biology Training Laboratory; a position he held thru 1996. In 1996, Dr. Mifflin joined the Division of Gastroenterology in the Department of Internal Medicine at UTMB. His current research focuses upon the biology of the intestinal subepithelial myofibroblast in the regulation of intestinal homeostasis.
Area of ResearchBiology of the Intestinal Subepithelial Myofibroblast: Research in the lab focuses upon the biology of intestinal myofibroblasts (IMF). These cells are members of a family of phenotypically interrelated cells that include glomerular mesangial cells, renal and pulmonary interstitial fibroblasts and hepatic stellate (perisinusoidal Ito) cells. Located at the interface between the epithelium and lamina propria, IMF modulate information transfer between these tissue compartments and play a pivotal role in immunology, physiology, development, and carcinogenesis of the gastrointestinal tract. These cells are likely to play an important role in the etiology of colon cancer, inflammatory bowel disease, and celiac disease. Ongoing projects involve:
- Regulation of cyclooxygenase-2 (COX-2) gene expression in IMFs. This research combines biochemical, molecular biological, and histochemical approaches to understand signaling pathways that regulate COX-2 in IMFs. This research is significant since COX-2 expression is observed in IMF during the early stages of colorectal carcinogenesis and the chemopreventive effects of nonsteroidal anti-inflammatory drugs derive from their ability to inhibit synthesis of COX-derived prostaglandins. This research is also important to understand signaling pathways in IMF that regulate expression of other factors important for regulating epithelial proliferation and modulating intestinal inflammation.
- Myofibroblasts as Determinants of the Intestinal Stem Cell Niche. We hypothesize that IMFs communicate with epithelial stem cells in normal tissue and cancer and regulate the level of proliferation and survival within this population. Via elaboration of soluble Wnt agonists and antagonists and BMP family members IMFs may represent important therapeutic targets in colorectal cancer and in normal intestinal tissue. One current focus of this project is to explore whether the combination of COX-2 inhibitors and Wnt pathway inhibitors effectively retards the growth rate of tumors by targeting proliferation and expansion of cancer stem cells.
1. Mifflin RC, Saada JI, Di Mari JF, Adegboyega PA, Valentich JD, Powell DW. Regulation of cyclooxygenase-2 expression in human intestinal myofibroblasts: Mechanisms of IL-1-mediated induction. Am J Physiol 282: C824-C834, 2002.
2. Adegboyega PA, Mifflin RC, Di Mari JF, Saada JI, Powell DW. Immunohistochemical study of myofibroblasts in normal colonic mucosa, hyperplastic polyps and adenomatous colorectal polyps. Arch Pathol Lab Med 126:829-836, 2002.
3. Di Mari JF, Mifflin RC, Adegboyega PA, Saada JI, Powell DW. IL-1a-induced COX-2 expression in human intestinal myofibroblasts is dependent on PKCz/ROS induction. Gastroenterology, 124:1855-1865, 2003.
4. Mifflin RC, Saada JI, Di Mari JF, Adegboyega PA, Valentich JD, Powell DW. NSAID-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol 65:470-478, 2004.
5. Adegboyega PA, Ololade O, Saada JI, Mifflin RC, Di Mari JF, Powell DW. Subepithelial myofibroblasts express COX-2 in colorectal tubular adenomas. Clin Canc Res 10:5870-5879, 2004.
6. Di Mari JF, Saada JI, Mifflin RC, Valentich JD, Powell DW. HETEs enhance IL-1-mediated COX-2 expression via augmentation of message stability in human colonic myofibroblasts. Am J Physol Gastrointest Liver Physiol 293:719-728, 2007.
7. Kosinsky G, Li VSW, Chan ASY, Zhang J, Ho C, Tsui WY, Chan TL, Mifflin RC, Powell DW, Yuen ST, Leung SY, Chen X. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Nat Acad Sci 104:15418-15423, 2007.
8.Kosinski C, Stange DE, Xu C, Chan AS, Ho C, Yuen ST, Mifflin RC, Powell DW, Clevers H, Leung SY, Chen X. Indian Hedgehog Regulates Intestinal Stem Cell Fate Through Epithelial-Mesenchymal Interactions During Development. Gastroenterology. 2010 Sep;139(3):893-903.
9. Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada J, West AB. Myofibroblasts I. Paracrine cells important in health and disease. Am J Physiol(Cell) 277:C1-C19, 1999.
10. Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada J, West AB. Myofibroblasts II. Intestinal subepithelial myofibroblasts. Am J Physiol(Cell) 277:C183-201, 1999.
11. Powell DW, Adegboyega PA, Di Mari JF, Mifflin RC. Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. Am J Physiol Gastrointest Liver Physiol. 89:G2-7, 2005.12. Mittal S, Mifflin R, Powell DW. Cancer stem cells: the other face of Janus. Am J Med Sci. 2009 Aug;338(2):107-112.
13. Powell DW, Pinchuk IV, Saada JI, Chen X, Mifflin RC. Mesenchymal cells of the intestinal lamina propria. Annual Review of Physiology. 2011;In Press.
14. Mifflin RC, Pinchuk IV, Saada JI, Powell DW. Intestinal myofibroblasts: Targets for stem cell therapy. Am J Physiol: GI and Liver Physiol. 2011;In Press.
The UTMB Center for Global Health Education (CGHE) is dedicated to the training of tomorrow's global health work force to improve health for the people of Texas and around the world. Check out their website for more information on the global health programs and education going on in our department.
The department of internal medicine is developing evidence based clinical protocols which will be available in EPIC (as order sets) for use when admitting patients with these diagnoses. Their AIM is to standardize care and decrease length of stay and readmission rates.Currently available protocols are:
- CAP - Community Acquired Pneumonia Orderset
- Congestive Heart Failure (CHF)
- Chronic Obstructive Pulmonary Disease (COPD)
- Diabetic Ketoacidosis Adult, ICU
- General Medicine Admission
- Immunodeficiency Flow Panel
- MICU/CCU Admission Order Set
- Oral Analgesic Medicaitons
- Parenteral Opioids
- Sepsis, Adult ICU
All protocols can be found in the EPIC order set section.
The department of Internal Medicine has a large role in the Meaningful Use Initiative. Our participation is key for the success of the initiative. Please visit the meaningful use website for important communication and updates from the Meaningful Use Initiative.