University of London/National Institute for Medical Research
Dept. of Neurobiology and Developmental Sciences,
and the Winthrop P. Rockefeller Cancer Institute,
University of Arkansas for Medical Sciences,
4301 W. Markham St. Slot 814,
Little Rock, AR 72205
Stem cells, cell cycle control and differentiation, vertebrate development, cancer biology, regulated mRNA translation, signal transduction and drug discovery
My research interests lie in understanding regulation of cell differentiation during both embryonic development as well as in the adult organism as it strives to maintain homeostasis or adapt to injury or changing organismal demands. We study regulation of signal transduction pathways as well as their targets within responding cells. Of late, our research has focused on control of specific mRNA translational control programs exerted by sequence-specific RNA binding proteins, including Musashi. By applying molecular biology techniques and proteomic approaches, we have sought to identify Musashi target mRNAs, elucidate the mechanism(s) by which Musashi exerts repression or activation of target mRNAs in a cell context-dependent manner and characterize the signaling pathways that control Musashi function. Our current studies seek to characterize the role of regulated mRNA translation in general, and Musashi specifically, in controlling stem cell function and cellular differentiation in the mammalian anterior pituitary gland as it adapts to meet the fluctuating hormonal needs of the body.
While stem cell self-renewal is directed and regulated at multiple levels, this process appears to be particularly sensitive to mechanisms that impinge upon the control of mRNA translation. However the co-associated factors mediating, and the molecular processes controlling, regulated mRNA translation remain poorly characterized. A better understanding of the molecular events governing regulated mRNA translation in stem cells may identify new druggable targets to enhance regeneration after injury and conversely, present new therapeutic opportunities to mitigate tumor growth or relapse after conventional treatment regimes.