Medical Student Research Fellowship for Summer 2008
Mentor: Kathlynn C. Brown
Department: Internal Medicine
Room number: ND2.110F (office), ND2.136 (lab)
Mail Code: 9185
Phone number: 214-645-6348
E-mail: Kathlynn.Brown@UTSouthwestern.edu
Project title: Targeted Therapies for the Treatment of Non-Small Cell Lung Cancer
Human subjects IRB approved project number (where applicable): N/A
Animal subjects IRB approved project number (where applicable): Yes APN approval number:
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 with animal work involved (tumor implantation, tumor growth,
and drug delivery)
Brief Description of Project:
Within the United States, 170,000 new cases of lung cancer are diagnosed each
year and 60% of these patients will die within one year. New modes of targeted-therapy
are needed to address this critical health care problem. One approach is to
develop "smart bullet" drugs that deliver therapeutics specifically
to the tumor while remaining silent to surrounding healthy tissues. Cell-specific
delivery of therapeutics has been shown to increase the efficacy of the drug
while decreasing its side effects. Furthermore, many pharmaceutical agents have
been developed, only to be abandoned as treatments due to high levels of toxicity
in vivo. Reduction of the amounts required for treatment could resurrect some
of these drugs from the shelves of pharmaceutical companies. Towards this goal
we have isolated 11 different peptides that bind to different non small cell
lung carcinoma (NSCLC) cell lines from a phage displayed peptide library. These
peptides are able to discriminate between cancerous and normal cells, and display
high cell specificities, even among tumors with the same pathological classifications.
Our data indicates that these peptides will have utility as targeting reagents.
The goal of this project is to utilize these peptides to develop effective drug
delivery systems for lung tumors.
Previous Research Activities or Publications with Medical Students:
I have had three MDs as postdoctoral fellows in the laboratory.
Previous Publications involving MD postdoctoral fellows:
" Elayadi, AN, Samli, KN, Prudkin, L, Liu, Y, Bian, A, Xie, X, Wistuba, II, Roth, JA, McGuire, MJ, Brown, KC. A peptide selected by biopanning identifies the integrin ?v?6 as a prognostic biomarker for non-small cell lung cancer. Cancer Res. 2007; 67:5889-5895.
" Oyama T, Rombel IT, Samli KN, Zhou X, Brown KC. Isolation of multiple cell-binding ligands from different phage displayed-peptide libraries. Biosensors & Bioelectronics 2006; 21:1867-1875.
" De J, Chang YC, Samli KN, Schissler J, Newgard CB, Johnston SA, Brown KC. Isolation of a mycoplasma-specific binding peptide from an unbiased phage-displayed peptide library. Mol Biosystems 2005;1:149-157.
" Oyama T, Sykes KF, Samli KN, Minna JD, Johnston SA, Brown KC. Isolation
of lung tumor specific peptides from a random library: generation of diagnostic
and cell-targeting reagents. Cancer Lett 2003;202:219-230.
" Zhou X; Chang Y-C, Oyama T, McGuire MJ, Brown KC. Cell-specific delivery of a chemotherapeutic to lung cancer cells. J Am Chem Soc 2004;126:15656-15657.
Recent Summer Interns:
Adam Monroe (currently chemistry major at Stanford University)
Naveen Pattisapu (currently biology major at the University of Texas at Austin)
Sapna George (currently in a combined medical degree program at the University
of Missouri at Kansas City)
Jonathan Li (currently biology major at the University of Texas at Austin)
Rachel Chirayil (currently business major at the University of Texas at Austin)