Anna Constance Vind

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My PhD research focused on a cellular signaling pathway called the ribotoxic stress response (RSR). The RSR surveys the structural and functional integrity of ribosomes, and when triggered it activates the MAP3 kinase ZAK leading to activation of MAP kinases p38 and JNK, and a subsequent pro-inflammatory response.    

I have been striving to uncover the mechanism underlying activation of RSR, and ZAKs role in it. Our current hypothesis is that ZAK surveils ribosome integrity by binding directly to ribosomal RNA loops. Here, we believe ZAK acts as a molecular ruler that measures the distance between the loops to detect ribosome stalling, upon which, ZAK auto-activates and initiate the MAP kinase signaling cascade.

In the clinic, ribotoxic stress occurs upon infection with the Shiga-like toxin-producing enterohemorrhagic Escherichia coli (EHEC). Infections with EHEC may result in severe disease such as hemolytic uremic syndrome, which can be fatal. We speculate that ZAK-mediated RSR signaling contributes to these detrimental clinical outcomes of EHEC infection. To investigate this, I currently reside in Boston, where I am evaluating the therapeutic potential of ZAK and RSR inhibition in treatment of EHEC infection in mice.