ACTIVE RESEARCH PROJECTS

PROJECT 1

Identifying small molecules that disrupt primary miR-18a and the RNA binding protein, hnRNP A1, interaction

Recently, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), was shown to selectively bind to the terminal loop of primary microRNA-18a to enable its processing to microRNA-18a. Although research has substantiated micriRNA-18a’s presence in cancer, no drug has been developed to validate its role and potential therapeutic relevance as a drug target. Therefore, we are designing a small molecule probe that will inhibit the primary-miRNA-18a – hnRNP A1 interaction so as to advance our knowledge of this interaction as a drug target. Currently, we are using two approaches: molecular modeling and high throughput screening.

PROJECT 2

Development of a preliminary microRNA-31 targeted small molecules for the treatment of colorectal cancer

microRNA-31 is an oncogenic microRNA that is overexpressed in colorectal cancer. This project is twofold:
1) We are adopting a high-throughput fluorescence-based Dicer assay to be used to identify a new lead microRNA-31 small molecule inhibitor. 
2) Recently a small molecule containing a phenylisoxazole sulfonamide core was identified as an inhibitor of microRNA-31 in colorectal cancer cells.  We are using this phenyliosoxazole sulfonamide compound as a scaffold for structure activity relationship studies to investigate the requirements needed to develop a potent and selective microRNA-31 small molecule inhibitor.