Medical Student Research Fellowship for Summer 2005
Mentor: Harold "Skip" Garner
Department: McDermott Center
Room number: NA2.508
Mail Code: 8591
Phone number: 81661
E-mail: garner@swmed.edu
Three projects
Project I title: Data mining driven drug discovery
Human subjects IRB approved project number (where applicable): We have several approval numbers through our collaborators.
Animal subjects IRB approved project number (where applicable): We have several approval numbers through our collaborators and several approval numbers of our own.
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): animal-based
Brief Description of Project:
We have developed a text data mining code, IRIDESCENT, that has the sum of all interactions among all biomedical objects (drugs, diseases, chemicals, genes, etc.) in all of Medline. We can query that network to discover hidden hypotheses. Focusing on drugs, we have demonstrated we can predict new uses for existing compounds, thus greatly reducing the time and money (currently it is 15 yrs, $880M for a new drug) required to 'discover' a new efficacy. We have been focusing on cardiac diseases (cardiac hypertrophy, myocardial infarction, fibrillation) that are underserved by existing therapeutics, and test these suggestions directly in appropriate mouse models for disease. We are also investigating cancer, dermatology and diabetes applications.
We propose a project that could involve one or more summer students to work with the group to test some new candidate drugs on some new disease indications. The work would involve experiment design, animal handling, data taking and analysis. It is desirable to complete an investigation such that a manuscript can be written on any positive results.
Project II title: Computational biology applications for basic and clinical researchers
Human subjects IRB approved project number (where applicable): We have several approval numbers through our collaborators.
Animal subjects IRB approved project number (where applicable): We have several approval numbers through our collaborators and several approval numbers of our own.
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
Brief Description of Project:
We have developed a series of computational biology/bioinformatics applications and databases. These include text data mining (IRIDESCENT and eTBLAST), polymorphism prediction for candidate gene selection, analysis methods for microarrays and mass spec, etc.
We propose a project will be to build modules to extend some of our resources. Specifically, we would like to expand the text on which we work from Medline to text sources that are more clinical, such as the Physicians Desk Reference, text books, etc. The research will involve writing scripts to properly incorporate this new data, and then inspect and evaluate the results of their work by extensive testing of the code. This work would then be made widely available to the global research community.
Project III title: Microsatellites and their role in alternative splicing
Human subjects IRB approved project number (where applicable): We have several approval numbers through our collaborators.
Animal subjects IRB approved project number (where applicable): We have several approval numbers through our collaborators and several approval numbers of our own.
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 using human cell lines
Brief Description of Project:
Alternative splicing is one possible explanation that reconciles the complexity 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.
Previous Research Activities or Publications with Medical Students:
The lab each year has enjoyed having a medical student for a summer research experience. Previous research activities include computational biology/bioinformatics research involving computations and laboratory validation, instrumentation development and laboratory validation.
They have successfully completed work, often ending in a publication. I also encourage (and suppor)t them to submit abstracts and produce a poster for the medical student research forum.
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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