The overarching goal of our laboratory is to understand the control of stem cells in development and diseases. Our research is focused on uncovering novel mechanisms of post-transcriptional and translational regulation during normal and malignant hematopoiesis. We aim to develop innovative therapeutic approaches targeting these regulatory pathways in leukemia and in cancer.
While disruption of genetic and epigenetic mechanisms and altered signaling networks are commonly studied, the role post-transcriptional and translational regulation in tumorigenesis has only recently recognized. We are particularly interested in defining the regulation of mRNA decay and translation mediated by poly(A) tail length and RNA deadenylation complexes and other RNA binding proteins in the context of normal and leukemia stem cells. Despite the central role of mRNA decay and poly(A) tails in regulating and coupling RNA metabolism and translation, it is virtually unknown how these processes contribute to drive and maintain the self-renewal and oncogenic gene expression programs in stem cells and cancer. Our work will provide insights into this largely unexplored area and enable development of new therapies. The laboratory employs human and mouse models; a broad range of molecular biology methods and a global approach using next generation sequencing techniques to decipher regulation of gene expression at multiple layers from transcription to mRNA biogenesis and translation.
