Cell & Developmental Biology
Cancer Cell Biology
Area of interest
- We have developed essential technologies for the study of the nascent field of non-coding RNA biology. These tools include molecular approaches for the identification and quantitation of RNA species, and bioinformatic tools for the analysis of next-generation sequencing data. We have also developed high throughput screening methods using shRNA and small molecule libraries to specifically address key questions in microRNA research.
- We have utilized these tools to address basic questions about non-coding RNA function in development and disease. My lab has focused on cancer using mammalian (cell based) systems; however, we have numerous collaborative projects to address a range of developmental questions and diseases in several model organisms.
Using this strategy, we have made many important discoveries, for example:
- Using a microRNA microarray of our own design, and more recently custom designed next generation sequencing methods, we have defined microRNA expression patterns in a myriad of biological states and diseases. Specifically, we identified microRNA alterations in cancer and in neurological disease. Among these alterations, we identified the miR-17-92 cluster as a key oncogenic driver for B-cell lymphoma. Recent work by many labs, including ours, has reinforced the role of this microRNA cluster in a range of cancer types.
- MicroRNA biogenesis occurs by action of the RNAse III enzymes Drosha and Dicer on the microRNA transcript. Using classic biochemical approaches, my lab has discovered multiple regulatory events that occur during these biogenesis steps, affecting the production of the mature microRNA species. Specifically, we identified the RNA binding protein Lin28 as a key regulator of the Let-7 family of miRNAs. We have also identified non-templated nucleotide modifications and covalent base modifications of specific microRNA species. Current work is focused on defining the role of these modifications in microRNA function, turnover, and transport into extracellular vesicles.
- In a collaborative project with the Deshmukh and Pearce laboratories we have developed a novel drug discovery platform for the discovery of small molecule compounds that alter expression of endogenous microRNAs. We are using this platform to identify new therapeutic directions for the treatment of cancer and neurological disease.