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 using the mouse model system. 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 in order to devote his efforts to full time research. His current research focuses upon the application of molecular biology techniques to clarify the role played by the intestinal subepithelial myofibroblast in the regulation of intestinal homeostasis.

Dr. Mifflin's research focuses upon the biology of intestinal myofibroblasts (IMF).These cells are members of a family of phenotypically interrelated cells which 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 :

1. Regulation of cyclooxygenase-2 (COX-2) gene expression in IMFs. This research combines biochemical, molecular biological, and histochemical approaches to understand signaling pathways which 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 which regulate expression of other factors important for regulating epithelial proliferation and modulating intestinal inflammation.

2. IMF as novel immune regulators. This area of research combines immunological, molecular biological, and histochemical approaches to understand how IMF interact with immune cells to modulate intestinal inflammation and possibly tolerance to dietary and bacterial antigens present in the intestinal lumen. Knowledge derived from these studies will be used to determine defects associated with IMF in IBD and celiac disease.

Dr. Mifflin is part of the Don Powell laboratory which consists of three GI faculty members (Drs. Di Mari, Mifflin, and Mr. Saada, who participate in the projects listed above and who are also developing independent projects related to the biology of IMF), a surgical pathologist (Dr. Adegboyega) and one postdoctoral.

1. Mifflin, R.C., Moller, P.C., and Papaconstantinou, J. 1988. Genetic analysis of L-ethionine-mediated induction of alpha-fetoprotein in mice. Somatic Cell and Mol.Gen. 14:553-566

2. Kurosky, A., Gorham, E.L., Van Heumen, W.R., Garcia, A.T., Smith, J.S., and Mifflin, R.C. 1997. Expression and genetic variation of the Aplysia egg-laying hormone gene family in the atrial gland. Invert.Neurosci. 2:261-271

3. Mifflin, R.C., and Kellems, R.E. 1991. Coupled transcription-polyadenylation in a cell-free system. J.Biol.Chem. 266:19593-19598

4. Alam, T., An, M.R., Mifflin, R.C., Hsieh, C.C., Ge, X., and Papaconstantinou, J. 1993. Trans-activation of the alpha 1-acid glycoprotein gene acute phase responsive element by multiple isoforms of C/EBP and glucocorticoid receptor. J.Biol.Chem. 268:15681-15688

5. Dai, B., Widen, S.G., Mifflin, R., and Singh, P. 1997. Cloning of the functional promoter for human insulin-like growth factor binding protein-4 gene: endogenous regulation. Endocrinology 138:332-343

6. Powell, D.W., Mifflin, R.C., Valentich, J.D., Crowe, S.E., Saada, J.I., and West, A.B. 1999. Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 277:C1-C19.

http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/referer?http://ajpcell.physiology.org/cgi/content/full/277/1/C1

7. Powell, D.W., Mifflin, R.C., Valentich, J.D., Crowe, S.E., Saada, J.I., and West, A.B. 1999. Myofibroblasts. II. Intestinal subepithelial myofibroblasts. Am J Physiol 277:C183-201

8. Mifflin, R.C., Saada, J.I., Di Mari, J.F., Adegboyega, P.A., Valentich, J.D., and Powell, D.W. 2002. Regulation of COX-2 expression in human intestinal myofibroblasts: mechanisms of IL-1-mediated induction. Am J Physiol Cell Physiol 282:C824-834.

http://ajpcell.physiology.org/cgi/content/full/282/4/C824

http://ajpcell.physiology.org/cgi/content/abstract/282/4/C824

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11880271

9. Adegboyega, P.A., Mifflin, R.C., DiMari, J.F., Saada, J.I., and Powell, D.W. 2002. Immunohistochemical study of myofibroblasts in normal colonic mucosa, hyperplastic polyps, and adenomatous colorectal polyps. Arch Pathol Lab Med 126:829-836.

http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=126&issue=7&page=829

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12088453

10. Di Mari, J., Mifflin, R., Saada, J., Adegboyega, P., and Powell, D. 2003. IL-1alpha-induced COX-2 expression in human intestinal myofibroblasts is dependent on a PKCzeta-ROS pathway. Gastroenterology 124:1855-1865

11. Mifflin, R.C., Saada, J.I., Di Mari, J.F., Valentich, J.D., Adegboyega, P.A., and Powell, D.W. 2004. Aspirin-Mediated COX-2 Transcript Stabilization via Sustained p38 Activation in Human Intestinal Myofibroblasts. Mol Pharmacol 65:470-478.

http://molpharm.aspetjournals.org/cgi/content/abstract/65/2/470

Address:	301 University Blvd., Galveston, Tx.77555-1064 Galveston, Texas 77555
Email:	rmifflin@utmb.edu
Office:	409-772-1501