Research Overview:

The Molecular Genetics, Cellular and Tissue Transplantation Lab, supervised by Dr. Leslie Krueger is a clinical and research lab. Diagnostic services are provided to the Solid Organ Tissue Transplantation Department of the Alfred I duPont Hospital for Children and genetic and biochemical research is conducted to provide insight into biochemical signaling pathways activated in certain types of cancer.

My research interest focuses on the Akt/PI3K/mTOR pathway, which is aberrantly activated in breast cancer. The specific aims of our work are to identify genes responsible for the modulation of the antineoplastic effects of rapamycin drug exposure. Our study uses the MDA-MB 468 (rapa-sensitive) and MDA-MB 231 (rapa-insensitive) breast cancer cell lines. We will use siRNA and miRNA transfections to understand regulation of gene product and the effects of the knockdown of genes involved in mTOR inhibition by rapamycin. We currently use real time PCR to monitor changes in miRNA and gene expression in transformed and drug treated cells and functional proteomics to investigate protein changes. In collaboration with Dr Deni Galileo, University of Delaware, we will develop retroviral and lentiviral systems for delivery of the selected siRNAs and miRNAs into mammalian cells which will be tested in an in vivo chick embryo model. The genetic and functional heterogeneity in the breast cancer population often hinders a single therapeutic intervention. Our study seeks to augment drug treatment with the targeting of specific genes to modulate expression levels. This, we propose can impact breast cancer therapy by minimizing drug resistance and maximizing tolerability to the patient.

Delaware Biotechnology Institute
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