Cancer Institute

  • Roy J. Duhé

    Professor of Pharmacology & Toxicology; Professor of Radiation Oncology
    Associate Director for Cancer Education
    Molecular Cancer Therapeutics Program
    PhD, Biochemistry, 1989, University of Wisconsin, Madison, WI
    Senior Fellow, 1990-93, University of Washington, Seattle, WA
    Scientist, 1993-99, National Cancer Institute - FCRDC; Frederick, MD

    Contact information
    2500 N State St, Room R406
    Jackson, MS 39216
    Phone: (601) 984-1625
    E-mail: rduhe@umc.edu

    duhe_roy.jpg

    Research interests

    • Regulation of enzymatic properties and functional roles of JAKs in cancers and other diseases
    • Interrelationships between redox regulation, energy metabolism and signal transduction pathways
    • Cancer education 

    Research synopsis

    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.

    Recent accomplishments and honors

    • 2011 - St. George National Award, American Cancer Society
    • 2007 - Diagnosis and Treatment of Cancer Award, Mississippi Partnership for Comprehensive Cancer Control
    • 2006 - Field Editor for Drug Design, Encyclopedia of Cancer, 2nd Edition, Manfred Schwab, editor

    Selected publications

    • Kundrapu K et al. Activation Loop Tyrosines Allow the JAK2(V617F) Mutant to Attain Hyperactivation. Cell Biochemistry and Biophysics 52, 103-112, 2008
    • Mamoon N et al. Multiple Cysteine Residues Are Implicated In Janus Kinase 2-Mediated Catalysis. Biochemistry 46, 14810-14818, 2007.
    • Lee S and Duhé RJ. Kinase Activity and Subcellular Distribution of a Chimeric Green Fluorescence Protein-Tagged Janus Kinase 2. Journal of Biomedical Science 13, 773-786, 2006.
    • Chatti K et al. Tyrosine phosphorylation of the JAK2 activation loop is essential for a high activity catalytic state, but dispensable for a basal catalytic state. Biochemistry 43, 4272-4283, 2004.
    • Smith JK et al. Emerging roles of targeted protein-tyrosine kinase inhibitors in cancer therapy. Oncology Research/Incorporating Anti-Cancer Drug Design 14, 175-225, 2004.