2006projectindexGarner

Medical Student Research Fellowship for Summer 2006

Mentor: Dr. Harold Garner
Department: McDermott Center
Room number: NA2.508
Mail Code: 8591
Phone number: 81661
E-mail: garner@swmed.edu

Three projects

Project I title: Microsattelites and their Role in Alternative splicing

Human subjects IRB approved project number (where applicable): Adi F. Gazdar, M.D. IRB File No. 191 36400 "Research Depository of Normal and Neoplastic Human Tissues" Approved Date: 2/15/2002

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

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:

Alternative splicing is one possible explanation that reconciles the complexity and differences between humans and other much lower species for which the human genome project has revealed to have the same number of genes. Further, replication, editing and repair functions can result in microsatellite instability and thus cancer. We have just shown using a bioinformatics analysis that there is a very significant correlation between exon skipping (a major form of alternative splicing) and the number of microsatellite repeats that form complementary pairs in introns that flank the exons of interest. We hope to demonstrate experimentally that this new mechanism is functional and manipulate-able. The approach will be to take DNA from several matched cancer/normal cell lines and measure the genotype of flanking microsatellites by DNA sequencing and the alternative splicing status (by quantitative PCR) for several candidate exons in genes that may play a role in cancer. This would lay the foundation for a genetic manipulation study where we will transfect different microsatellies (of different repeat lengths) into a specific cell line and show that it proportionately alters the splicing ratio.

Project II title: Text data mining for repurposing drugs

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

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

Brief Description of Project II:

We have developed a platform for implicit knowledge discovery and central to that is a software package called IRIDESCENT. Using this package we analyzed all of Medline and other text to identify indirect (implicit) relationships among various biomedical objects (drugs, diseases, chemicals, genes, etc.). The package has now been partially optimized to identify new uses of existing drugs in a variety of clinical areas (heart disease, cancer, arthritis, epilepsy, etc.). We have validated some of the predictions in mouse models of cardiac hypertrophy and myocardial infarction.

We wish to expand the functionality of the software package, to improve its sensitivity and add features that enable users to make better selections of drugs to test in the laboratory. We also want to expand its database to include literature from other areas of science (IOP and NASA abstracts) and test its utility in those areas as well. The medical student will be expected to work on the original code, database development, and use their medical knowledge to assure that their work is optimized for drug discovery by medical researchers. We further want the medical student to apply their knowledge in computer science to quantitatively evaluate the performance of the system in a number of tests aimed to show its specificity and sensitivity.

Project IIItitle: Platform for Nanomedicine

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

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

Brief Description of Project:

We will measure the cellular response to sub-cellular (organelle) deposition of drugs which have been made light sensitive, and thus we can activate them at organelle resolution. You would have to work to make a certain drug photosensitive, modify some instrumentation we have now to project at a higher resolution, etc. A TI Digital Light Processor based projection technology will be used at 365 nm and will be modified to achieve approximately 1 micron resolution, enabling us to target subcellular compartments. This will all be mated to a epi-fluorescence microscope to monitor the cells response in real time, including the motion and response of certain proteins labeled with quantum dots.

Previous Research Activities or Publications with Medical Students:
Hyperspectral Imaging: A Novel Approach for Microscopic Analysis, R.A. Schultz, T. Nielsen, J. Zavaleta, R. Ruch, R. Wyatt, H.R. Garner., Cytometry 43: 239-247 (2001)
K. M. O'Brien, J. Wren, V. K. Dave, D. Bai, R. D. Anderson, S. Rayner, G. A. Evans, A. E. Dabiri, and H. R. Garner, "ASTRAL, a Hyperspectral Imaging DNA Sequencer," Review of Scientific Instruments, Vol. 69, No. 5, May, 1998.
Elizabeth M. Flood, Robert S. Kumar, Rashmi Shah, Quinlan Amos, Jonathan D. Wren, Ralph V. Shohet, and Harold R. Garner, Melatonin administration does not affect isoproterenol-induced left ventricular hypertrophy in a mouse model, submitted, Cardiovascular Research.

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