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Ramachandran Murali, PhD
Director, Molecular Therapeutics Core, Immunology Research
Research Scientist, Biomedical Imaging Research Institute
|Associate Professor, Biomedical Sciences|
Awards and Activities
|CDMRP Breast Cancer (DOD)||2012|
|Molecular Cancer Therapeutics||Current|
|International Union for Crystallography||1996|
Molecular basis of cancer metastasis and identification of new therapeutic strategies to limit resistance, recurrence of cancer. Studies are focused on role of the tumor necrosis factor receptors and the epidermal growth factor receptors in breast, lung and pancreatic cancers. Employ structural biology for drug discovery and develop molecular probes for tumor imaging and drug delivery.
Developed small peptidomimetics of Herceptin and small molecule probes to tumor necrosis factor receptors. The small molecular probes are being engineered for cancer diagnosis, and treatment of breast cancer and autoimmunity pathologies. Developed a novel drug discovery platform, "cavity-induced allosteric modification" for a new class of allosteric inhibitors of protein complexes.
Current investigations include:
Co-regulation of ErbB and RANK, RANKL , osteoprotegrin (OPG) and TRAIL receptor complexes in breast, lung and pancreatic cancers. Small molecular probes have been developed targeting these receptor complexes using structural biology techniques, and the current investigations include developing therapeutics and strategies for tumor imaging and nanoparticles for tumor-specific drug delivery.
- Takasaki W, Kajino Y, Kajino K, Murali R, Greene MI: Structure-based design and characterization of exocyclic peptidomimetics that inhibit TNF alpha binding to its receptor. Nat. Biotechnol., 15(12): 1266-70, 1997
- Park BW, Zhang HT, Wu C, Berezov A, Zhang X, Dua R, Wang Q, Kao G, O'Rourke DM, Greene MI, Murali R: Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo. Nat. Biotechnol., 18(2): 194-8, 2000
- Cheng X, Kinosaki M, Takami M, Choi Y, Zhang H, Murali R: Disabling of receptor activator of nuclear factor-kappaB (RANK) receptor complex by novel osteoprotegerin-like peptidomimetics restores bone loss in vivo. J. Biol. Chem., 279(9): 8269-77, 2003
- Murali R, Cheng X, Berezov A, Du X, Schön A, Freire E, Xu X, Chen YH, Greene MI: Disabling TNF receptor signaling by induced conformational perturbation of tryptophan-107. Proc. Natl. Acad. Sci. U.S.A., 102(31): 10970-5, 2005
- Levine DH, Ghoroghchian PP, Freudenberg J, Zhang G, Therien MJ, Greene MI, Hammer DA, Murali R: Polymersomes: a new multi-functional tool for cancer diagnosis and therapy. Methods, 46(1): 25-32, 2008
- Ponde DE, Su Z, Berezov A, Zhang H, Alavi A, Greene MI, Murali R: Development of anti-EGF receptor peptidomimetics (AERP) as tumor imaging agent. Bioorg. Med. Chem. Lett., 21(8): 2550-3, 2011