Harjot Singh
Research Mentor(s): Erin Janssen
Mentor Department: Pediatrics
Authors: Harjot Singh, Amy Pichardo De Leon, Andrew Livingston, Maria Beamer, Erin Janssen
Session: Session 1 (9:00am – 9:50am)
Presentation Type: Poster 120
Abstract
DOCK8 and STAT5B are two important signaling proteins that play a role in immune cell regulation. Patients with DOCK8 deficiency develop food allergies, severe atopic dermatitis, and are prone to severe viral and bacterial infections. DOCK8 activates CDC42, and via CDC42 activation, DOCK8 has important roles in regulating the actin cytoskeleton, cell migration, and cell-cell interactions. Our lab has also shown that DOCK8 plays a role in STAT5B activation downstream of IL-2 signaling and may therefore have important functions in cytokine signaling. IL-2 is important for proliferation of T lymphocytes as well as regulatory T cell (Treg) maintenance and function, and patients with STAT5B deficiency have severe immune dysregulation. We propose that DOCK8 through the activation of the CDC42-regulated kinase, PAK2, DOCK8 regulates the phosphorylation and thereby activation of STAT5B. To investigate this hypothesis, we will employ a multi-faceted approach, including mouse models of DOCK8 deficiency, cell lines overexpressing DOCK8, STAT5B, and related signaling proteins, and cell-free protein expression systems to explore direct protein-protein interactions through co-immunoprecipitation. Our preliminary data demonstrated the presence of a DOCK8, STAT5, PAK2 complex in T cells. Currently, we are investigating the possible interaction of STAT5B with SHP2 phosphatase. Through co-immunoprecipitation, we will determine how a mutation in STAT5B (mimicking PAK2 phosphorylation) affects the binding of SHP2. These results will provide a foundation for understanding how alterations in these interactions in the DOCK8-deficiency lead to immune dysregulation. This research has broad implications for therapeutic development, as it sheds light on potential targets for treating immune-related disorders.
