Amnon Altman, Ph.D.

I have a long, ~30-year record of studying T cell activation and signal transduction, including the use of preclinical mouse models of inflammatory/autoimmune and malignant diseases. My group was the first (in parallel with another group) to report the essential role of early tyrosine phosphorylation in T cell activation (Science, 1990). Work in my laboratory led to the discovery of several novel signaling molecules (PKC-theta in 1993, PICOT in 2000, and SLAT in 2003) and several novel protein-protein interactions (14-3-3 with PI3-K, Cbl with PKC-theta; Syk with Vav1 and 3BP2; and PKC-theta with SPAK kinase and CD28). We were the first to report a discrete biological activity (i.e., NFAT activation) of the oncogenic form of the Cbl E3 ligase, (J. Biol. Chem., 1997). Of note, we recently defined the molecular basis for the highly selective recruitment of PKC-theta to the central region of the Teff cell immunological synapse via its physical association with CD28, and demonstrated that this localization is critical for PKC-theta-mediated signaling (Nat. Immunol. 2011). In 2013, my laboratory published a comprehensive review article on PKC-theta and its therapeutic implications in Advances in Pharmacology. In the course of our work, my laboratory has generated many retroviral, mammalian and bacterial expression vectors for multiple mutated and chimeric forms of PKC-theta, including GFP-tagged versions. More recently, we identified PKC-eta as being critical for certain (contact-dependent) suppressive pathways mediated by regulatory T cells (Treg) via its physical interaction with CTLA-4, a prominent target for cancer immunotherapy, and elucidated, in part, the underlying mechanism (Nat. Immunol. 2014, J. Clin. Invest. 2017).