Yina H. Huang

DEPARTMENT OF Pathology & Immunology
Keywords: cancer, immune response, natural killer cells, inositol polyphosphates

Cancer therapies typically either enhance the immune response to transformed cells or directly target tumor growth. I am interested in investigating the ability of inositol polyphosphates to both enhance cytotoxicity by Natural Killer cells and alter tumor growth. My interests extend from my initial observations which identified a novel role for IP4 in T cells. IP4 is formed by ItpkBmediated phosphorylation of IP3, a second messenger critical for Ca2+ mobilization. Strikingly, soluble IP4 is structurally identical to the head group of the membrane lipid PIP3, which recruits Pleckstrin homology (PH) domain-containing proteins to the membrane. This similarity has led us to propose that IP4 serves as a soluble analog of PIP3. Indeed, we find that IP4 is a physiologically important second messenger with two main functions 1) to limit IP3 levels and 2) to bind PH domains in the cytosol and promote their recruitment to membrane PIP3. Using proteomics, our lab has identified many other IP4 binding proteins. An active area of investigation is determining how IP4 regulates normal activation and transformation.