University of California, Riverside

School of Medicine

Faculty Biographies

Maurizio Pellecchia

Daniel Hays Endowed Chair in Cancer Research
Professor of Biomedical Sciences

Maurizio Pellecchia

University of California, Riverside
Riverside, CA 92521

Tel: (951) 827-7829
Office: 0317 School of Medicine Research Building

Education and Training

  • Fellowship, University of Michigan, Ann Arbor, Michigan
  • Fellowship, European Molecular Biology Organization, ETH Zürich (Swiss Federal Institute of Technology), Zurich, Switzerland
  • Ph.D., Pharmaceutical Chemistry, University of Naples Federico II, Naples, Italy
  • M.S., Organic Chemistry, University of Naples Federico II, Naples, Italy

Research Summary

Our laboratory focuses on the design, synthesis and evaluation of novel pharmacological tools in the areas of cancer, neurodegeneration, and potentially other disease areas, using innovative drug discovery approaches. The overall goal of the laboratory is to bring together basic sciences including modern nuclear magnetic resonance spectroscopy (NMR) techniques, x-ray crystallography, computer modeling, traditional medicinal synthetic chemistry, and cell-biology to elucidate the molecular basis of disease and to design novel pharmacological tools that serve for target validation and to develop novel therapeutic agents. A central theme of our laboratory is the development of novel methodologies to tackle protein-protein interactions (PPIs) as targets for drug discovery, and to further advance our most promising agents into potential therapeutics.

Examples of our most recent and exciting studies can be summarized as follows:

  1. We developed several powerful approaches and strategies to ligand design that seem particularly suited for tackling challenging drug targets, such as those involved in protein-protein interactions. 
  2. Using our approaches, we discovered, optimized and characterized several potential therapeutic compounds targeting proteins of the Bcl-2 family, such as Mcl-1, Bfl-1, and Bcl-2. These agents are potentially very useful in overcoming cancer resistance to radiation or chemotherapy. We are investigating their efficacy to treat CLL (Chronic Lymphocytic Leukemia), melanoma, prostate, breast, pancreatic, and lung cancers.
  3. We are developing novel agents that aim at inhibiting cancer metastases by targeting a number of genes that are involved in migration and adhesion of cancer cells to other tissues (EphA2, SIAH, MDA-9/syntenin, PEX domain of MT1-MMP, CD44, Tcl-1, ROR1, etc.). These agents are being developed and tested in models of melanoma, CLL, prostate and pancreatic cancers.
  4. We developed innovative targeted delivery approaches based on the EphA2 receptor. Conjugation of these delivery agents with chemotherapeutic drugs selectively deliver the cytotoxic agents to cancer cells, while sparing normal cells. In mice xenograft models, this approach increases the efficacy and reduces side effects (increase the therapeutic window) of chemotherapy.  The approach is being developed with various chemotherapeutic drugs currently in use as first line treatment (taxol, gemcitabine, fluradarabine, doxorubicine, etc.) against pancreatic cancer, prostate cancer, breast cancer, renal carcinoma, melanoma, CLL, and potentially other tumors.
  5. We developed novel and potent agents targeting the EphA4 receptor. These agents can find therapeutic utility in certain type of cancers (stomach cancer), in spinal cord injury, and neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s Disease. Our agent is currently being developed into a potential therapeutic against ALS by Iron Horse Therapeutics, Inc.

Awards, Honors and Service

  • Adjunct professor, Sanford-Burnham-Prebys Medical Discovery Institute, 2015-present.
  • Associate editor: Frontiers in Cancer Molecular Targets and Therapeutics, 2008-present.
  • Adjunct professor, University of California, San Diego, CA 92037, Dept. of Pathology, School of Medicine, 2007-present.
  • Associate editor: AACR, Molecular Cancer Therapeutics, 2007-present.
  • Permanent member, NCI Drug Discovery and Molecular Pharmacology review panel, 2012-2016.
  • Scientific Founder, Iron Horse Therapeutics, Inc., 2015.
  • Associate director of translational research, NCI-designated Cancer Center, Sanford-Burnham-Prebys Medical Discovery Institute, 2015.
  • Distinguished lecturer, University of Hawaii, NCI-designated Cancer Center, 2015.
  • Teacher of the Year Award, Graduate School of Biomedical Sciences, Sanford-Burnham-Prebys Medical Discovery Institute, 2014.
  • Associate dean for curriculum and member of the executive committee, Graduate Program of Biomedical Sciences, Sanford-Burnham Medical Research Institute, 2006-2014.
  • Keynote speaker, Fragment-Based Ligand Design (FBLD) conferences, 2011 & 2012.
  • Founder, AnCoreX Therapeutics, 2011.
  • NIH High-End Instrument Grant award, 2008.
  • William R. Hearst Foundation Award, 2003.
  • Fellow, European Molecular Biology Organization(EMBO), 1996-1998.

Selected Publications

  • Wu B, Wang S, De SK, Barile E, Quinn BA, Zharkikh I, Purves A, Stebbins JL, Oshima RG, Fisher PB, Pellecchia M. Design and Characterization of Novel EphA2 Agonists for Targeted Delivery of Chemotherapy to Cancer Cells. Chem & Biol. 2015 Jul 23;22(7):876-87. doi: 10.1016/j.chembiol.2015.06.011. PMID:26165155
  • Barile E, Pellecchia M. NMR-based approaches for the identification and optimization of inhibitors of protein-protein interactions. Chemical reviews. 2014;114(9):4749-63. PMCID: 4027952
  • Wu B, Zhang Z, Noberini R, Barile E, Giulianotti M, Pinilla C, Houghten RA, Pasquale EB, Pellecchia M. HTS by NMR of combinatorial libraries: a fragment-based approach to ligand discovery. Chem &  Biol. 2013;20(1):19-33. doi: 10.1016/j.chembiol.2012.10.015. PubMed PMID: 23352136; PMCID: 3966493.
  • Wang S, Noberini R, Stebbins JL, Das S, Zhang Z, Wu B, Mitra S, Billet S,Fernandez A, Bhowmick NA, Kitada S, Pasquale EB, Fisher PB, Pellecchia M. Targeted delivery of paclitaxel to EphA2-expressing cancer cells. Clinical cancer research. 2013;19(1):128-37. doi: 10.1158/1078-0432.CCR-12-2654. PubMed PMID: 23155185; PMCID: 3537892.
  • Stebbins JL, Santelli E, Feng Y, De SK, Purves A, Motamedchaboki K, Wu B, Ronai ZA, Liddington RC, Pellecchia M. Structure-based design of covalent Siah inhibitors. Chem & Biol. 2013;20(8):973-82. doi: 10.1016/j.chembiol.2013.06.008. PubMed PMID: 23891150; PMCID: 3763817.
  • Rega MF, Wu B, Wei J, Zhang Z, Cellitti JF, Pellecchia M. SAR by interligand nuclear overhauser effects (ILOEs) based discovery of acylsulfonamide compounds active against Bcl-x(L) and Mcl-1. Journal of medicinal chemistry. 2011;54(17):6000-13. doi: 10.1021/jm200826s. PubMed PMID: 21797225; PMCID:3165075.
  • Placzek WJ, Wei J, Kitada S, Zhai D, Reed JC, Pellecchia M. A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy. Cell death & disease. 2010;1:e40. doi: 10.1038/cddis.2010.18. PubMed PMID: 21364647; PMCID: 3032312.
  • Stebbins JL, De SK, Machleidt T, Becattini B, Vazquez J, Kuntzen C, Chen LH, Cellitti JF, Riel-Mehan M, Emdadi A, Solinas G, Karin M, Pellecchia M. Identification of a new JNK inhibitor targeting the JNK-JIP interaction site. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(43):16809-13. doi: 10.1073/pnas.0805677105. PubMed PMID: 18922779; PMCID: 2567907.
  • Pellecchia M, Bertini I, Cowburn D, Dalvit C, Giralt E, Jahnke W, James TL, Homans SW, Kessler H, Luchinat C, Meyer B, Oschkinat H, Peng J, Schwalbe H, Siegal G. Perspectives on NMR in drug discovery: a technique comes of age. Nature reviews Drug discovery. 2008;7(9):738-45. doi: 10.1038/nrd2606. PubMed PMID: 19172689; PMCID: 2891904.
  • Becattini B, Culmsee C, Leone M, Zhai D, Zhang X, Crowell KJ, Rega MF, Landshamer S, Reed JC, Plesnila N, Pellecchia M. Structure-activity relationships by interligand NOE-based design and synthesis of anti-apoptotic compounds targeting Bid. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(33):12602-6. doi: 10.1073/pnas.0603460103. PubMed PMID: 16891420; PMCID: 1567925.
  • Becattini B, Kitada S, Leone M, Monosov E, Chandler S, Zhai D, Kipps TJ, Reed JC, Pellecchia M. Rational design and real time, in-cell detection of the proapoptotic activity of a novel compound targeting Bcl-X(L). Chem. & biol. 2004;11(3):389-95. doi: 10.1016/j.chembiol.2004.02.020. PubMed PMID: 15123268.
  • Pellecchia M, Sem DS, Wuthrich K. NMR in drug discovery. Nature reviews Drug discovery. 2002;1(3):211-9. doi: 10.1038/nrd748. PubMed PMID: 12120505.

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