Academic Appointments

  • Basic Life Science Research Associate, Biology

All Publications

  • SETD5-Coordinated Chromatin Reprogramming Regulates Adaptive Resistance to Targeted Pancreatic Cancer Therapy. Cancer cell Wang, Z., Hausmann, S., Lyu, R., Li, T. M., Lofgren, S. M., Flores, N. M., Fuentes, M. E., Caporicci, M., Yang, Z., Meiners, M. J., Cheek, M. A., Howard, S. A., Zhang, L., Elias, J. E., Kim, M. P., Maitra, A., Wang, H., Bassik, M. C., Keogh, M. C., Sage, J., Gozani, O., Mazur, P. K. 2020


    Molecular mechanisms underlying adaptive targeted therapy resistance in pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Here, we identify SETD5 as a major driver of PDAC resistance to MEK1/2 inhibition (MEKi). SETD5 is induced by MEKi resistance and its deletion restores refractory PDAC vulnerability to MEKi therapy in mouse models and patient-derived xenografts. SETD5 lacks histone methyltransferase activity but scaffolds a co-repressor complex, including HDAC3 and G9a. Gene silencing by the SETD5 complex regulates known drug resistance pathways to reprogram cellular responses to MEKi. Pharmacological co-targeting of MEK1/2, HDAC3, and G9a sustains PDAC tumor growth inhibition in vivo. Our work uncovers SETD5 as a key mediator of acquired MEKi therapy resistance in PDAC and suggests a context for advancing MEKi use in the clinic.

    View details for DOI 10.1016/j.ccell.2020.04.014

    View details for PubMedID 32442403

  • SnapShot: Lysine Methylation beyond Histones MOLECULAR CELL Biggar, K. K., Wang, Z., Li, S. 2017; 68 (5): 1016-+


    Lysine methylation is a prevalent post-translational modification (PTM) used by the cell to reversibly regulate protein function. Although it has been extensively studied in the context of histones and the associated chromatin, the remaining methyllysine proteome remains largely unexplored. This SnapShot provides an overview of the current state of lysine methylation research and its emergence as a dynamic PTM occurring on histone and non-histone proteins.

    View details for PubMedID 29220647