The ABEL is focused on the analysis and application of nucleic acid-based technologies. Our goals are the understanding of critical biophysical and biochemical parameters involved in these processes and, in turn, the tuning of these parameters to achieve an improved technology. The current foci of the lab fall into two categories: i) mechanistic analysis of RNA interference (RNAi) and ii) parallel analytical platforms for cellular molecules. Specific ongoing projects include:

1.) in vitro interactions of RNAs with recombinant human TRBP, PACT, and DGCR8
TRBP, PACT, and DGCR8 are known to participate in RNA interference (RNAi) and micro RNA processing. We are investigating the binding of these recombinant proteins to siRNAs of varying sequence and structure to identify what are the important interactions that lead to strong inhibition of target expression.

2.) Molecular Barcode-labeled aptamers for parallel protein measurements
Proteomics is the measurement of all proteins in a sample. Current technologies for proteomics are usually laborious, and important information can be lost due to incomplete protein separation. We are combining two existing technologies, molecular barcodes (MBs) and aptamers, to develop a new technology for parallel protein measurements using oligonucleotide microarrays. MBs are a set of unique DNA labels that can be used to detect a single nucleic acid species from a mixed population. Aptamers are high affinity nucleic acid molecules that can bind to specific target proteins. The goal of our current research is to generate MB-containing aptamers and use them to measure the concentrations of several proteins simultaneously.

3.) Quantitative, genomics-based measurement of transcription factor levels
Inappropriate/unregulated expression of transcription factors (TFs) has been implicated in many diseases, including cancer, AIDS, and diabetes. Current methods for measurement of TF expression are inadequate for simultaneous measurement of all relevant proteins. Our work seeks to provide a genomics-based, parallel method for the measurement of TF expression using MBs and microarrays. This method will also be useful for analysis of TF binding affinities for their consensus and mutated target sequences.

4.) Delivery of siRNAs by polymeric nanoparticles
The instability of biological molecules, in particular RNAs, often limits their utility as therapeutics. However, incorporation of these molecules into delivery vectors can enhance their chemical, biological, and pharmacokinetic stability. We are investigating the use of novel polymeric nanoparticles for the delivery of siRNAs to cells in culture and in vivo.