Tumor Immunobiology, Drug Discovery, Targeted Therapy, Biomarker and Signal Transduction
The long-term goal of the Murali Laboratory is to understand the structural and molecular basis of cancer mediated by immune system and cellular growth machinery using structural biology. The Murali Lab’s guiding philosophy is that the complex molecular events mediated by ErbB receptors and some members of the tumor necrosis factor receptor superfamily (TNFRSF) are responsible for tumor growth, resistance and metastasis of several solid tumors including those of breast, prostate, pancreas and lung cancer. Antibody-based immunotherapy has revolutionized cancer therapy and autoimmune disorders. However, the antibodies are inadequate to address resistance, recurrence and metastasis of cancer, which requires a combination of drugs aimed at 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. The Murali Lab studies the biological effects of protein complexes through structural perturbation using pharmacological probes. The lab’s structure-based drug discovery will complement needed therapies in cancer treatment.
The Murali Laboratory has been pursuing studies to understand the molecular basis of 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, the lab has developed small molecules including peptide mimics to disable the TNF, Fas, OPG/RANKL/TRAIL and ErbB receptors’ functions.
Currently, the Murali Laboratory has extended our studies to target constitutively activated transcription factors responsible for resistance to therapy and metastasis of cancer. Our efforts are focused on developing small molecule probes to disable functions of transcription factors relevant for breast, brain and prostate cancers. These small molecules are being explored as a therapeutic strategy for tumor metastasis.