Medical Student Research Fellowship for Summer 2009

Mentor: John D. Minna, M.D.
Department: Hamon Center for Therapeutic Oncology Research
Room number: NB8.206
Mail Code: 8593
Phone number: 214 648-4900
E-mail: john.minna@utsouthwestern.edu
Project title: Defining the Molecular Pathogenesis of Lung Cancer Through Genetic Manipulation of Human Bronchial Epithelial 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) = Basic research

Brief Description of Project:
Genome wide studies of mRNA expression and DNA copy number and methylation analyses have shown that human lung cancers has multiple acquired genetic and epigenetic changes. A major problem is to sort out which of these are the most important and which are potential new therapeutic targets for lung cancer. To approach this we have developed a new series of immortalized human bronchial and peripheral airway epithelial cells (HBECs and HSAECs) from over 40 different persons. These grow in chemically defined media, clone with high efficiency, can be genetically manipulated, and can differentiate in 3 D organotypic cultures into respiratory epithelium. However, they do not form colonies in soft agar (anchorage independent growth) or tumors in immune deprived mice. This project involves preparing isogenic derivatives of these cells through inserting defined oncogenes and defined tumor suppressor gene changes alone and in various combinations. The resulting cells are tested in a variety of biologic and molecular biologic assays for progression toward malignancy. In addition, the cells are examined using genome wide microarray techniques for changes in the expression of all human genes to identify both biomarkers for the presence of the specific oncogenic changes and also potential therapeutic targets. The research student fellowship will involve learning about clinical and molecular biologic aspects of lung cancer and how to develop new clinically useful biomarkers and targeted therapy in addition to a large number of laboratory techniques including cell culture, transfections, tumorigenicity assays, preparation and handling of nucleic acids, and expression assays as well as bioinformatic techniques. The student will work closely with post doctoral fellows, graduate students, and technicians expert in these approaches and will participate in the lung cancer disease oriented team at UTSW.

Previous Research Activities or Publications with Medical Students:

Drug sensitivity phenotypes of lung cancer; development of methods for organotypic culture differentiation of human bronchial epithelial cells; development of radiation sensitivity phenotypes of mRNA signatures predicting response to radiation therapy.