Research

The completion of the human genome project leads to the realization that only a small percentage of our heritable DNA sequences encodes proteins. Instead of being “junk DNA”, a significant portion of the genome is transcribed into the so-called non-coding RNAs. Emerging pieces of evidence indicate that these RNA molecules, although lacking protein-coding capacity, play important roles in regulating the genomic output. MicroRNAs are one class of tiny non-coding RNAs that are ~21 nucleosides in length and are often highly conserved among species. They recognize sites in messenger RNAs, and by doing so, regulate translation and/or target mRNA abundance.

In our laboratory, we aim to understand how microRNAs and other non-coding RNAs regulate mammalian cell fate choices during differentiation, and how alterations in such regulations lead to human diseases, with an emphasis on cancer. We use the blood system as one of our models. Hematopoietic stem cells undergo a series of fate choices during its differentiation to give rise to all mature blood cells, whereas changes in the differentiation program can cause malignancies such as leukemia. We use a set of genomic tools to dissect how microRNAs may control these processes. We combine the information from genome-wide microRNA expression analyses and microRNA functional genomics screens to derive candidates for functional characterization. In addition, we study the role of large non-coding RNAs in these processes.

Another area of interest is the differentiation of embryonic stem cells. ES cells and induced pluripotent cells possess the ability to differentiate into all cell types , holding the promise for cell replacement therapy. MicroRNAs are dynamically regulated during ES cell differentiation. In addition, we have shown that microRNAs direct mammalian lineage choices. Projects in the lab aim to understand the role of microRNAs in modulating the differentiation outcome of ES cells.

We are also interested to use bioinformatics to understand basic microRNA mechanisms. A current project focuses on the analysis of common microRNA and messenger RNA profiling data from a large cohort of samples, aiming to derive rules on microRNA biogenesis, termination and crosstalk with canonical protein-coding gene pathways.