Michael Dennis, PhD

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    Research interests

    The overall goal of the laboratory of Dr. Michael Dennis is to identify the molecular mechanisms and signaling pathways that contribute to altered gene expression patterns in disease states, with a particular emphasis on diabetes. Studies funded by the American Diabetes Association and National Institutes of Health have primarily focused on exploring the impact of post-translational modification (i.e., phosphorylation and O-GlcNAcylation) of eukaryotic translation initiation factors (eIFs) in mediating a shift from cap-dependent to cap-independent mRNA translation.

    The Dennis laboratory has also actively explored regulation of the master kinase mammalian target of rapamycin (mTOR) and its impact on gene expression in response to nutrients and growth factors.

    Recent publications demonstrate that whole body genetic ablation of the translational repressor 4E-BP1 or the stress response protein REDD1, which regulates 4E-BP1 action, is sufficient to prevent visual dysfunction in rodent models of type 1 diabetes. This is at least in part because 4E-BP1 and REDD1 regulate hyperglycemia-induced expression of the pro-angiogenic cytokine VEGF, which plays a major causal role in the development of the microvascular complications.

    Elucidation of these translational control mechanisms is expected to validate new targets for the development of a new generation of therapeutics aimed at addressing the molecular basis of diabetic retinopathy.

    While recently developed antibody-based therapeutics designed to block VEGF signaling have improved diabetic retinopathy treatment outcomes, up to half of patients fail to fully respond to anti-VEGF therapies. This is at least in part because VEGF levels poorly correlate with the extent of retinal edema, implying that additional factors are likely to play a role in disease pathology. The hope is that recently identified small molecule inhibitors may be used to counter diabetes-induced initiation factor defects, and thus not only prevent the increase in VEGF translation, but also impact the expression of other homeostatic and trophic factors in retina.

    Expertise related to UN Sustainable Development Goals

    In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

    • SDG 3 - Good Health and Well-being


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