Catholic University of America
PhD Student in Immunology
NFκB is a transcription factor that plays a pivotal role both innate and adaptive immune responses. Dysregulated NFκB signaling drives many disorders of the immune system, can disrupt the balance of inflammation and tolerance, and is the primary causative factor in many types of leukemia and lymphoma. Despite the importance of the NFκB signaling pathway in immune function, the precise mechanisms that engage specific branches of the NFκB pathway remain unclear.
My project is to clarify how antigenic stimuli direct NFκB activation via the NFκB Essential Modulator protein (NEMO). NEMO is a critical adapter protein that regulates the kinases responsible for promoting translocation and activation of canonical NFκB molecules. For my project, I will take advantage of the many dynamic imaging techniques available in the lab, and will visualize the movement of fluorescently tagged NEMO mutants in activated T cells in real time. By using a panel of existing and custom-generated mutants, I will be able to study the localization of NEMO relative to the T-cell receptor (TCR), receptor-proximal signaling complexes, and scaffolds with documented roles in NFκB activation. Our preliminary data indicates that NEMO interacts directly with the TCR, and that this interaction requires the ability of NEMO to interact with specific ubiquitin polymers. The loss of TCR recruitment correlates with impairments of NFκB activation. My goal is to explore how poly-ubiquitination and phosphorylation cooperate to determine the localization of NEMO and the activity of the NEMO-associated IκB kinases. Ultimately, we intend to determine the biological significance of the recruitment of this complex to the TCR itself.
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