Maurizio Pellecchia's 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.
Maurizio Pellecchia's Bio
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 SBP 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.
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.
Placzek WJ, Wei J, Kitada S, Zhai D, Reed JC, Pellecchia M
Cell Death Dis 2010 May 6 ;1:e40
Yuan H, Johnson SL, Chen LH, Wei J, Pellecchia M
Chem Biol Drug Des 2010 Sep 1 ;76(3):263-8
NMR-based design and evaluation of novel bidentate inhibitors of the protein tyrosine phosphatase YopH.
Leone M, Barile E, Vazquez J, Mei A, Guiney D, Dahl R, Pellecchia M
Chem Biol Drug Des 2010 Jul ;76(1):10-6
Reduction of Circulating Cancer Cells and Metastases in Breast-Cancer Models by a Potent EphA2-Agonistic Peptide-Drug Conjugate.
Salem AF, Wang S, Billet S, Chen JF, Udompholkul P, Gambini L, Baggio C, Tseng HR, Posadas EM, Bhowmick NA, Pellecchia M
J Med Chem 2018 Mar 8 ;61(5):2052-2061
Wu B, De SK, Kulinich A, Salem AF, Koeppen J, Wang R, Barile E, Wang S, Zhang D, Ethell I, Pellecchia M
Cell Chem Biol 2017 Mar 16 ;24(3):293-305
Inhibition of radiation-induced glioblastoma invasion by genetic and pharmacological targeting of MDA-9/Syntenin.
Kegelman TP, Wu B, Das SK, Talukdar S, Beckta JM, Hu B, Emdad L, Valerie K, Sarkar D, Furnari FB, Cavenee WK, Wei J, Purves A, De SK, Pellecchia M, Fisher PB
Proc Natl Acad Sci U S A 2017 Jan 10 ;114(2):370-375
Nakanishi Y, Reina-Campos M, Nakanishi N, Llado V, Elmen L, Peterson S, Campos A, De SK, Leitges M, Ikeuchi H, Pellecchia M, Blumberg RS, Diaz-Meco MT, Moscat J
Cell Rep 2016 Sep 20 ;16(12):3297-3310
Baggio C, Barile E, Di Sorbo G, Kipps TJ, Pellecchia M
ChemMedChem 2016 May 19 ;11(10):1097-106
Novel therapy of prostate cancer employing a combination of viral-based immunotherapy and a small molecule BH3 mimetic.
Sarkar S, Pradhan A, Das SK, Emdad L, Sarkar D, Pellecchia M, Fisher PB
Oncoimmunology 2016 Mar ;5(3):e1078059