Laura Gillespie

The MIER family of transcriptional regulators and their role in cell differentiation and cancer progression

The central theme of my research program is to define how specific sets of genes (gene programs) are coordinately regulated at the molecular level to produce a particular cellular response, whether it be to differentiate, to proliferate or to migrate.

Polypeptide growth factors are known to be involved in many of these cellular activities. Furthermore, it has become apparent that many of the known oncogenes are growth factors, their cellular receptors or components of their intracellular signaling pathways. Thus, elucidation of the regulatory mechanisms governing the cellular response to growth factors will further our understanding of how misregulation can lead to cancer.

Our work on fibroblast growth factor (FGF)-regulated cell differentiation led to the discovery of a novel transcription/chromatin regulatory molecule called Mesoderm Induction Early Response 1 (MIER1)^1-3. We have since determined that one of its isoforms, MIER1α, specifically interacts with estrogen receptora (ERα) and represses its transcriptional activity⁴. Moreover, MIER1α is a powerful inhibitor of estrogen-stimulated growth of breast carcinoma cells⁴, demonstrating that it has the potential to play a critical role in the development and progression of breast cancer⁵. The current research in my lab is focused on elucidating the molecular aspects of MIER1α function and its link to breast cancer progression.
Two additional family members have now been identified: mier2 and mier3. Little is known about the proteins encoded by these 2 genes however our initial studies support the idea that MIER2 and MIER3 also have vital roles in transcriptional regulation⁶. Currently, my lab is investigating their function by characterizing the MIER2 and MIER3 transcriptional regulatory complexes, as a first step towards elucidating their molecular, cellular and physiological functions.