Medical Student Research Fellowship for Summer 2003

Mentor: Drs. Maria-Ana Ghetie and Ellen S. Vitetta
Department: Cancer Immunobiology Center
Room Number: NB9.210
Mail Code: 8576
Phone Number: 214-648-1200
E-mail: Maria-Ana.Ghetie@UTSouthwestern.edu and Ellen.Vitetta@UTSouthwestern.edu

Project title: To determine how the anti-CD20 monoclonal antibody, Rituxan, reverses multidrug resistance (MDR).

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): (JF to add)

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:

The goal of the present project is to study the mechanisms underlying the ability of an anti-CD20 MAb (Rituxan) to reverse multiple drug resistance (MDR) in a human B-lymphoma. P-gp is the protein in the membrane of MDR tumor cells which pumps chemotherapeutic drugs out of the cells. Recently it was demonstrated that cholesterol- and sphingolipid-rich membrane microdomains (lipid rafts) appear to function as platforms for induction and regulation of several signaling cascades. Several proteins have been identified in lipid rafts, and P-gp is one of them. We hypothesize that anit-CD20 MAb causes of P-gp to leave lipid rafts, so that it is no longer active. Studies in progress support this hypothesis and results have important implications for treating drug resistant relapsed lymphomas. This project will involve studying the molecular mechanisms underlying this affect.

Previous Research Activities or Publications with Medical Students: (M. Ghetie/E. Vitetta)

Mark Lowe (1993)
Elizabeth Vaught (1995)
Sami Arslanlar (1996)
Blake Sanders (1997)
Michalle Crank (2002)

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