Laboratory RESEARCH


   Our lab research is focused on developing novel biochemical approaches toward understanding the role of RNA molecules in normal cell biology, as well as disease.

   Recent observations in the community have demonstrated that RNA molecules can perform a myriad of functions, beyond providing genetic information from the genome to the ribosome. Small non-coding RNAs can regulate many steps of gene regulation, from transcription initiation to RNA degradation. The existence of a large class of RNAs with potential regulatory functions is now widely accepted. These functions range broadly from guiding genomic targeting of chromatin-modifying factors to scaffolding the assembly of ribonuclear protein complexes (RNPs). However, where the RNAs bind chromatin, what proteins they interact with and how their structures confer function is still largely undiscovered.

   Technological innovations are needed to further understand the role of RNA molecules in regulating basic biological function. Further, there is a need to expand the biochemistry toolkit to understand how large groups of RNAs are working in parallel inside living cells.

   Our goal as a lab is to merge seemingly disparate disciplines: chemistry & genomics, to gain novel insights into RNA structure and function. We always begin our projects with particular biological questions in mind. We use these questions to start our "catalytic cycle of discovery". We then design small molecules that will help us start to answer our questions. Biochemical approaches are then used to test our molecules and identify the best probe or conditions for in cell analyses. We then merge the chemical reactivity of our probes with deep sequencing to obtain a systems level analysis of RNA biology. The information we learn from our studies help up to refine our understanding of RNA biology, with the ultimate goal of obstainign new questions that prime the next round of our "catalytic cycle of discovery".

In line with our research goals described above, we are currently focused on the following questions:
1) How do RNA expression patterns change, in a cell-type specific manner, to control organ-level changes due to the environment?
2) How does RNA structure control the biology of large groups of RNA?
3) Where are RNAs localized within living cells?
4) How do RNA-protein networks combinatorially control RNA biology?

   It is our overall goal to develop methods that drive not only our research forward, but the research of many other labs. Technolgies are unique in that they can be viewed as "hypothesis generators", providing the community with novel targets and genes to explore in great detail. Future efforts down the road will be focused on understanding how we can take the information that we have learned and expand it toward the goal of developing therapies that control or inhibit deleterious RNA functions.

   For more information, please email Professor Spitale at rspitale@uci.edu