Request for Funding

Medical Student Research Fellowship for Summer 2000

Mentor: Robert Ilaria, Jr., M.D.

Department: Internal medicine; Molecular Biology

Room number: NB8.114

Mail Code: 8593

Phone number: 81632

E-mail: RILARI@mednet.swmed.edu

Project title: 1. The role of STAT signaling in Bcr/Abl transformation

                   2. Characterization of the MAPK and PI3K signaling pathways in EWS/FLI-1 transformation

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type        Basic research

Brief Description of Project:

We currently have two projects amenable to summer research

1. We and others have identified that Bcr/Abl, the fusion protein implicated in chronic myelogenous leukemia (CML) and 25% of the cases of adult acute lymphocytic (ALL), activates the STAT signaling pathway. STAT5 has been identified as the major STAT activated by the 210 kD form of Bcr/Abl (CML), while STAT6 is activated by the 190 kD form (ALL). We have preliminary data showing that STAT6 activation is important for P190 Bcr/Abl transformation. This research project will involve examining bone marrow cells from STAT6 knock out animals to determine why they are resistant to Bcr/Abl transformation. Techniques that will be learned during the project include: 1) using an in vitro BM colony assay to assay the transformation of BM cells in vitro. 2) retroviral gene transfer to introduce the BCR/ABL oncogene into BM cells 3.) western blot analysis to confirm Bcr/Abl and STAT expression

2. We have recently discovered that the mitogen-activated protein kinase (MAPK) pathway is activated in cells transformed by EWS/FLI-1. EWS/FLI-1 encodes a mutant transcription factor, and is the oncogene identified in the vast majority of tumors from patients afflicted with Ewing’s sarcoma, the second most common malignant bone tumor of childhood. This project will involve characterizing the mechanisms by which EWS/FLI-1 activates MAPK signaling. Techniques that will be learned during the project include: 1) preparation of protein lysates from EWS/FLI-1 cell lines 2) western blot analysis of these cell lines for activation of other members of the ras signaling cascade. 3) basic DNA cloning 4) Reverse-transcriptase-based PCR.

Previous Research Activities or Publications with Medical Students:

Have supervised a variety of medical students during laboratory rotations.

Return to UT Southwestern Homepage

Return to Student Research Projects Index