Medical Student Research Fellowship for Summer 2009

Mentor: Jerry W. Shay, PhD. and Andres Roig, M.D.
Department: Cell Biology
Room number: L4.204
Mail Code: 9039
Phone number: 8-3282
E-mail: Jerry.Shay@utsouthwestern.edu
Project title: Characterization of human intestinal stem cells

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Brief Description of Project: Basic Research
Long-term propagation and characterization of normal human intestinal stem cells
Hypothesis: The failure of success in propagating intestinal stem cells has been due to the lack of appropriate in vitro conditions for their growth. We have recently developed methods for the long-term propagation and immortalization of normal human intestinal epithelial cells.
Specific aim 1: The medical student will characterize the stem cell nature of the isolated intestinal epithelial cells and will test the ability of the cells to proliferate long-term (using clonogenicity assays) and to differentiate in 2D monolayer culture
Specific aim 2: The medical student will develop methods for the 3D (organotypic) culturing of established intestinal stem cells and to characterize their ability to differentiate into functional cell types.

Dr. Roig, a physician scientist that will be officially on Faculty at UTSW in Internal Medicine as of July 1, 2009 will directly supervise the daily experiments of the student. Almost all the methods are well established in the laboratory except the 3D differentiation assays. The isolation and characterization of the stem and progenitor cells of the intestine will be important in understanding their role in biology and diseases of the intestine and to eventually develop therapies using the stem or progenitor cells to contribute to intestinal healing.

Previous Research Activities or Publications with Medical Students:

Tsakiri, K.D., Cronkite, J.T., Kuan, P.J. Xing, C., Ganesh, R., Weissler, J.C., Rosenblatt, R.L. Shay, J.W. Garcia, C.K. Adult-onset pulmonary fibrosis caused by mutations in telomerase , PNAS, USA, 104:7552-7557, 2007.

Jackson, S.R, Zhu, C-H., Paulson,V., Watkin, L., Dikmen, Z.G., Gryaznov, S.M., Wright, W.E., Shay, J.W. Anti-adhesive effects of GRN163L - an oligonucleotide, N3'-P5' thio-phosphoramidate targeting telomerase. Cancer Res. 67:1121-1129, 2007.

Robertson, D.M., Li, L, Fisher, S, Pearce, V.P., Shay, J.W., Wright, W.E., Cavanagh, H.D., Jester, J.V. Characterization of growth and differentiation in a telomerase-immortalized human corneal epithelial cell line. Investigative Ophthalmology and Visual Science 46:470-478, 2005.

Aisner, D.L., Wright. W.E. and Shay, J.W. Telomerase regulation: Not just flipping the switch Cur. Opin. Gen. Dev., 12:80-85, 2002. (issue cover image)