Medical Student Research Fellowship for Summer 2006


Mentor: Dr Robert Bachoo MD., PhD
Department: Neurology and Medicine
Room number: ND3.300
Mail Code: 9186
Phone number: 214-645-6309
E-mail:robertbachoo@utsouthwestern.edu
Project title: Role of EGFR in Gliomagenesis

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable):N/A

Project Type: Basic Research. Cell culture based studies and In-vitro assays. Studies will involve primary cultures of Astrocytes, Neurons and Neural stem cells, as well as human glioma cell lines.

Brief Description of Project:

Glioblastoma Multiforme (GBM) is the most common primary malignant tumor of the central nervous system with a dismal prognosis. Despite maximal surgical resection, radiation and chemotherapy the meidian survival from time of diagnosis is 1 year. The molecular pathogenesis of GBM involves mutations in pathways involving proliferation, cell cycle progression and apoptosis. Amplification of the epidermal growth factor receptor (EGFR) gene is a signature lesion of GBM. EGFR gene amplification and rearrangements are detected in 40-50% of cases of GBM, resulting in high levels of expression of wild type as well as mutant forms of the receptor. Recent efforts in molecularly targeted cancer therapies has led to the development of an EGFR specific inhibiotor(s) which show efficacy in subset of lung cancers, also bearing the same EGFR mutation.

During this summer, Nitin Singla, working in my lab., will undertake cell culture based studies which focus on signal transduction pathways activated by EGFR and how EGFR specific inhibitors may disrupt these oncogenic pathways. The broad goal of his work will be contribute to our efforts to arrive at a clear understanding of how EGFR transmits its oncogenic signal and to asses the efficacy and mechanisms of action of preclinical investigational EGFR specific inhibitors. It is expected that Nitin will be able to contribute to a body of work which will be submitted to peer review for publication and that he would be appropriately credited for his academic contributions.

During this summer's rotation, Nitin will work closely with a post-doc in my lab (Xiao-Li Yang) and 2 experienced senior research associates. Then will assist him in every facet of the labs activities. He will also interact with me on a daily basis. He will attend the weekly multidisciplinary Brain Tumor conference which has a strong 'teaching' emphasis and is attended by senior members from Neurosurgery, Radiology, Radiation Oncology and Neuropathology, as well as weekly conferences in Neuroscience and Developmental Biology.


Previous Research Activities or Publications with Medical Students:

Bachoo, R., Maher, E., Ligon, K., Sharpless, N., Chan, S., You, M., Tang, Y.,
DeFrances, J., Stover, E., Weissleder, R., Rowitch, D., Louis, D., DePinho, R.
Epidermal Growth Factor Receptor and Ink4a/Arf: Convergent mechanisms
governing terminal differentiation and transformation along the neural stem cell to
astrocyte axis. Cancer Cell 2002; 1(3): 269-277

Bachoo R., Kim R., Ligon K., Maher E., Brennan C., Billings N., Chan S., Li C., Rowitch D., Wong W., DePinho R. Molecular diversity of astrocytes with implications for neurological disorders. PNAS 2004; 101(22): 8384-8389

E. Strover and N.Billings were Medical students at Harvard Medical School, Boston.



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