Print Version
MAURIZIO PELLECCHIA, PH.D.
Professor
Infectious Diseases
858.646.3159 (phone)
858.795-5225 (fax)
mpellecchia@burnham.org
RESEARCH FOCUS, BIOGRAPHY, PUBLICATIONS
Research Focus
Dr. Pellecchia’s research focuses on the characterization of intermolecular interactions, on the determination of protein structures and on the development of small molecule inhibitors of protein targets involved in cell-signaling, virulence factors and host-pathogens interactions. The resulting compounds are then used as molecular probes to provide further understanding on the mechanism of action of their respective targets. The overall goal of the laboratory is to successfully bring together basic sciences involving modern nuclear magnetic resonance spectroscopy (NMR) techniques, computer modeling and traditional medicinal chemistry to elucidate the molecular basis of disease and to develop novel therapeutic compounds. Amongst the several projects that Dr. Pellecchia’s laboratory have initiated in the past years, noteworthy are the discovery, characterization and further development of potential therapeutic compounds targeting proteins of the Bcl-2 family, such as Bcl-xL and Bcl-2 (cancer targets) as well as Bid (involved in neurodegenerative diseases) and protein kinases such as p38 and Jnk (inflammation and diabetes). In addition, other very active areas of research involve the development of antitoxin compounds targeting the Anthrax metalloproteinase LF and protein components of the type-III secretion system, common to many pathogens, including Yersinia pestis and Salmonella. Finally, an area in which Dr. Pellecchia remains particularly interested is the development of novel NMR-based techniques to aid the characterization of protein structure, protein-protein and protein-ligand interactions using NMR spectroscopy. The design and synthesis of several high affinity ligands, for example, was made possible by the SAR by ILOEs approach, a NMR-based method developed in Dr. Pellecchia’s laboratory that enables the identification of high affinity ligands for a given protein target.
Biography
Dr. Pellecchia is a medicinal chemist with a strong background in biophysics and NMR-based drug design. He trained at the University of Naples (Italy) where he obtained his Ph.D. in Pharmaceutical Sciences, at the ETH-Zurich (working with 2002 Nobel Laureate Prof. Dr. Kurt Wüthrich) and the University of Michigan. Prior to his recruitment at the Burnham Institute for Medical Research as Associate Professor, Dr. Pellecchia spent a few years in the pharmaceutical industry. Dr. Pellecchia was promoted to full Professor in June 2007. Dr. Pellecchia's laboratory is centered on the characterization of intermolecular interactions, protein structure and on the development of small molecule inhibitors in systems involved in cell-signaling and apoptosis for the treatment of several human diseases including cancer, neurodegeneration and infectious diseases.
Selected Publications
Vazquez J. Tautz L., Mustelin T., Vuori K. and Pellecchia M. Design, synthesis and characterization of novel spin-labeled probes for the development of tyrosine phosphatase inhibitors. J. Med. Chem. (2007), in press
Chen J, Zhang Z, Stebbins JL, Zhang X, Hoffman R, Moore A, Pellecchia M. A fragment-based approach for the discovery of isoform-specific p38alpha inhibitors. ACS Chem Biol. 2007 May 22;2(5):329-36. Epub 2007 Apr 27.
Becattini B, Culmsee C, Leone M, Zhai D, Zhang X, Crowell KJ, Rega MF, Landshamer S, Reed JC, Plesnila N, and Pellecchia M. SAR by ILOEs-based design and synthesis of anti-apoptotic compounds targeting Bid. PNAS (2006) 12602-12606.
Leone M, Crowell KJ, Chen J, Jung D, Chiang GG, Sareth S, Abraham RT, and Pellecchia M. The FRB domain of mTOR: NMR-solution structure and inhibitor design. Biochemistry (2006) 45: 10294-10302.
Leone M, Yu EC, Liddington R, and Pellecchia M. NMR assignment of the phosphotyrosine binding (PTB) domain of tensin. J Biological NMR (2006) 36 Suppl 1:40.
Johnson, SL, Pellecchia M. Structure- and Fragment-Based Approaches to Protease Inhibition. CTMC 2006, 6: 317-329.
Becattini B, Pellecchia M. SAR by ILOEs: An NMR-Based Approach to Reverse Chemical Genetics. Chemistry. 2006, 12: 2658-62.
Forino, M., Jung, D., Easton, J.B., Houghton, P.J., and Pellecchia, M. (2005). Virtual docking approaches to protein kinase B inhibition. J Med Chem 48, 2278-2281.
Reed, J.C., and Pellecchia, M. (2005). Apoptosis-based therapies for hematological malignancies. Blood. 106, 408-418.
Fattorusso, R., Jung, D., Crowell, K.J., Forino, M., and Pellecchia, M. (2005). Discovery of a novel class of reversible non-peptide caspase inhibitors via a structure-based approach. J Med Chem 48, 1649-1656.
Forino M, Johnson S, Wong TY, Rozanov DV, Savinov AY, Li W, Fattorusso R, Becattini B, Orry AJ, Jung D, Abagyan RA, Smith JW, Alibek K, Liddington RC, Strongin AY, Pellecchia M. (2005) Efficient synthetic inhibitors of anthrax lethal factor. Proc Natl Acad Sci U S A 102(27):9499-504. Epub 2005 Jun 27.
Pellecchia M. (2005) Solution Nuclear Magnetic Resonance Spectroscopy Techniques for Probing Intermolecular Interactions. Chem Biol 12(9):961-71.
List of Publications via PubMed
(NIH National Library of Medicine)
