Aline Sandouk

Nuclear GRB2 as a Transcriptional Regulator and Functional Modulator of T Cells Biography

Growth factor receptor-bound protein 2 (GRB2) is a cytoplasmic adaptor protein present in all human cells whose aberrant function is linked to a multitude of cancers and chronic diseases. In human T cells, GRB2 regulates the formation of signaling complexes at the plasma membrane. GRB2 deficiency in T cells inhibits clustering of key signaling components following T cell receptor (TCR) activation, leading to downstream inhibition of calcium influx and cytokine production critical for effector activity. Although GRB2 is traditionally considered a protein of predominant cytoplasmic importance, emerging evidence reports the presence of GRB2 in the nucleus of various cell types. Preliminary data from our laboratory has shown that GRB2-deficient T cells exhibit little to no expression of IFN-γ protein or mRNA, which could not be reversed using agents that bypass early TCR signaling to induce activation. This suggests that an inability to express IFN-γ is not due to defects in membrane signaling but to events further upstream, at the level of the nucleus. However, no studies to date have investigated the nuclear function of GRB2. To this end, we seek to determine the mechanisms underlying nuclear translocation, regulation, and function of GRB2 as a driver of transcriptional regulation and functional modulation of T cells. A better understanding of this unexplored nuclear role of GRB2 may uncover novel disease mechanisms and empower us to develop novel interventions for lethal and life-limiting disorders associated with abnormal GRB2.

Aline Sandouk
Fairfax, VA
BS, Chemistry, George Mason University
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375 Newton Road
Iowa City, IA 52242
United States

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