Professor of Pharmacology & Toxicology Professor of Radiation Oncology Associate Director for Cancer Education(601) 984-1625
My research in personalized, molecularly-targeted chemotherapy focuses on “who, when and how” questions surrounding dysregulated Janus kinase (JAK) activity in cancers. The JAK/STAT/SOCS signaling axis is important in many cancers, and the therapeutic outcome of JAK-targeted therapy will depend upon the specific cancer subtype, the stage of cancer progression and the influence of JAK-interacting biomolecules in both the cancer and surrounding tissue. We therefore seek predictive biomarkers to distinguish patients who should receive such drugs from those who should avoid them. Our site-directed mutagenesis and enzymology studies reveal that JAK’s enzymatic properties and responses to inhibitors are highly dependent on its enzymatic activity state, which is normally controlled by covalent modifications such as phosphorylation and oxidation/reduction, as well as by mutations reported in human cancers. This information is vital for the rational design of effective next-generation JAK-targeted drugs.Our recent identification of a novel redox-sensor switch in JAK led us to examine the circumstances in which oxidative stress alters JAK signaling, and the medical consequences of this phenomenon. Given the importance of reactive oxygen species in radiotherapy, chronic inflammation and in other aspects of cancer, we are expanding our research into the nexus of redox regulation, signal transduction and energy metabolism. This will allow us to better anticipate how novel therapeutic agents, with targets ranging from JAK2 to 20-hydroxyeicosatetraenoic acid (20-HETE), can be effectively integrated into clinical cancer treatment modalities.