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Tumor biology, targeted therapy, biomarker, cell cycle and signal transduction
Our long-term goal is to understand the structural and molecular basis of cancer mediated by immune system and cellular growth machinery using structural biology. Our guiding philosophy is that the complex molecular events mediated by ErbB receptors and tumor necrosis factor receptor superfamily (TNFRSF) is responsible for growth, resistance and metastasis of several solid tumors including breast, ovarian, prostate, pancreas and lung. Antibody-based immunotherapy has revolutionized cancer therapy and autoimmune disorders. However, the antibodies are inadequate to address resistance, recurrence and metastasis of cancer. The evolving strategy for the treatment is a combination of drugs targeting multiple targets.
Structure-based drug discovery is one of the central problems in the field of structural biology. In particular, developing small molecular drugs targeting protein-protein/DNA complexes remains a challenging problem. Our interests are to study the biological effects of the receptor complexes through structural perturbation using pharmacological probes. Our structure-based drug discovery will complement the need in the cancer treatment.
We have been pursuing studies to understand the molecular basis of tumor necrosis factor receptor super family (TNFRSF) function, which plays a pivotal role in inflammation, autoimmunity and cancer. Over the years, using techniques from computational biology, X-ray crystallography and molecular biology, we developed small molecules including peptide mimics to disable the TNF, Fas, OPG/RANKL/TRAIL and ErbB receptors’ functions.
Currently, our studies are focused on the structural and molecular basis of OPG/RANKL/TRAIL and activated K-Ras/ErbB receptors' function in breast, lung and pancreatic cancers. Small molecule probes are used to study how members of TNFRSF regulate tumor growth and whether TNFRSF cooperatively functions with K-Ras/ErbB receptors. Furthermore, receptor-modifying peptidomimetics are also engineered for tumor detection and therapy.