个人简介

PhD, Brown University, Providence, RI MS, Duke University, Durham, NC AB, College of the Holy Cross, Worcester, MA

研究领域

Medicinal Chemistry and Chemical Technology

Prof. Pollastri’s primary research focus is on discovery of new therapeutics for neglected tropical diseases, using a “parachute” or “repurposing” approach. In this approach, he identifies parasitic targets of importance that have been previously biochemically validated, with a further focus on those targets with human homologs that have been pursued in human drug discovery. Prof. Pollastri’s lab then prepare known ligands previously reported against the human homolog for assessment against the parasite target, and then pursue an optimization program from that starting point. His lab’s first project is focused on trypanosomal phosphodiesterases, enzymes that have ~30% homology to human PDE4 and 5. Other projects focus on trypansomal TOR, Aurora kinases, dihydrofolate reductase, and HDACs. Prof. Pollastrli’s secondary area of focus is on chemical technologies. Projects in this category include diversification of lead compounds using reaction screening approaches, applications of flow chemistry, and Green Chemistry.

近期论文

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‡Ochiana, S.O.; Bland, N.D.; Settimo, L.; Campbell, R.K.; Pollastri, M.P. Repurposing human PDE4 inhibitors for neglected tropical diseases. Evaluation of analogs of the human PDE4 inhibitor GSK-256066 as inhibitors of PDEB1 of Trypanosoma brucei. Chemical Biology & Drug Design. In Press ‡Silva, L.; ‡Tanner, A.; Merritt, C.; Stuart, K.; Pollastri, M.P. Protein kinases as druggable targets in protozoan parasites. Chemical Reviews, In Press. Invited review. Diaz, R.; ºLuengo-Arratta, S.A.; ºSeixas, J.D.; ºAmata, E.; ‡Devine, W.; Cordon-Obras, C.; Rojas-Barros, D.I.; Jimenez, E.; Ortega, F.; Crouch, S.; Colmenarejo, G.; Fiandor, J.M.; Martin, J.J.; Berlanga, M.; Gonzalez, S.; Manzano, P.; Navarro, M.; Pollastri, M.P. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign. PLOS Neglected Tropical Diseases. In Press. Parks, A.J.; Pollastri, M.P.; Hahn, M.E.; Stanford, E.A.; Franks, D.G; Haigh, S.E.; Narasimhan, S.; ºAshton, T.D.; †Hopper, T.G.; Kozakov, D.; Beglov, D.; Vajda, S.; Schlezinger, J.J.; Sherr, D.H. In Silico Identification of an Aryl Hydrocarbon Receptor (AhR) Antagonist with Biological Activity In Vitro and In Vivo. Molecular Pharmacology. In press. ºAmata, E.; Bland, N.D.; †Hoyt, C.T.; Settimo, L.; Campbell, R.K.; Pollastri, M.P. Repurposing human PDE4 inhibitors for neglected tropical diseases: Design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors. Bioorganic and Medicinal Chemistry Letters. In press. Gaun, V.; Patchen, B.; Volovetz, J.; Zhen, A.W.; Andreev, A.; Pollastri, M.P.; Fraenkel, P.G. A chemical screen identifies small molecules that regulate hepcidin expression. Blood Cells, Molecules and Diseases 2014, In press. Galvin, B.D.; Li, Z.; Villemaine, E.; Poole, C.B.; Chapman, M.S.; Pollastri, M.P.; Wyatt, P.G.; Carlow, C.K.S. A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes. PLOS Neglected Tropical Diseases 2014, 8, e3145 Pollastri, M.P. Finding New Collaboration Models for Enabling Neglected Tropical Disease Drug Discovery. PLoS-Neglected Tropical Diseases 2014, 8, e2866. ºSeixas, J.D.; ºLuengo-Arratta, S.A.; Diaz, R.; Saldivia, M.; Rojas-Barros, D.I.; Manzano, P.; Gonzalez, S.; Berlanga, M.; Smith, T.K.; Navarro, M.; Pollastri, M.P. Establishment of a structure-activity relationship of the NVP-BEZ235 chemotype as a lead for African sleeping sickness. Journal of Medicinal Chemistry 2014, 57, 4834-4848. ºPatel, G.; Roncal, N.E.; Lee, P.J.; Leed, S.E.; Erath, J.; Rodriguez, A.; Sciotti, R.J.; Pollastri, M.P. Repurposing human Aurora kinase inhibitors as leads for anti-protozoan drug discovery. MedChemComm 2014, 5, 655 – 658. Lowe, M.M.; Mold, J.E.; Kanwar, B.; Huang, Y.; Louie, A.; Hahn, M.E.; Pollastri, M.P.; ºWang, C.; ºPatel, G.; Frank, D.G.; Schlezinger, J.; Sherr, D.; Silverstone, A.E.; McCune, J.M. Identification of an Endogenous Aryl Hydrocarbon Receptor Ligand That Drives Th22 Differentiation. PLoS One 2014, 9, e87877. Woodring, J.L.; Bland, N.D.; Ochiana, S.O.; Campbell, R.K.; Pollastri, M.P. Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1). Bioorg. Med. Chem. Lett.2013, 23, 5971 Patel, G.; Karver, C.E.; Behera, R.; Guyett, P.; Edwards, P.; Roncal, N.E.; Mensa-Wilmot, K.; Pollastri, M.P. Kinase scaffold repurposing for neglected disease drug discovery: Discovery of an efficacious, lapatanib-derived lead compound for trypanosomiasis. J. Med. Chem.2013 http://pubs.acs.org/doi/abs/10.1021/jm400349k Andriani, G.; Amata, E.; Beatty, J.; Clements, Z.; Coffey, B.J.; Courtemanche, G.; Devine, W.; Erath, J.; Juda, C.E.; Wawrzak, Z.; Wood, J.; Lepesheva, G.I.; Rodriguez, A.; Pollastri, M.P. Antitrypanosomal lead discovery: Identification of a ligand-efficient inhibitor of Trypanosoma cruzi CYP51 and parasite growth. J. Med Chem. 2013, 56, 2556 http://dx.doi.org/10.1021/jm400012e Katiyar, S.; Kufareva, I.; Behera, R.; Ogata, Y.; Pollastri, M.P.; Abagyan, R;. Mensa-Wilmot, K. Lapatinib-binding Protein Kinases in the African Trypanosome: A General Method for Identification of Targets for Kinase-Directed Drugs in a Cell. PloS One, 2013, 8, e56150. Ochiana, S.O.; Pandarinath, V.; Wang, Z.; Kapoor, R.; Ondrechen, M.J.; Ruben, L.; Pollastri, M.P. The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing. Eur. J. Med. Chem. 2013, 62, 777-784. Wang, C.; Ashton, T.D.; Gustafson, A.; Bland, N.D.; Ochiana, S.O.; Campbell, R.K.; Pollastri, M.P. Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 1. Sildenafil analogs. Bioorg. Med. Chem. Lett. 2012. http://dx.doi.org/10.1016/j.bmcl.2012.01.119 Ochiana, S.O.; Gustafson, A.; Bland, N.D.; Wang, C.; Russo, M.J.; Campbell, R.K.; Pollastri, M.P. Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs. Bioorg. Med. Chem. Lett. 2012. http://dx.doi.org/10.1016/j.bmcl.2012.01.118 Bland, N. D.; Wang, C.; Tallman, C.; Gustafson, A. E.; Wang, Z.; Ashton, T. D.; Ochiana, S. O.; McAllister, G.; Cotter, K.; Fang, A. P.; Gechijian, G.; Garceau, N.; Gangurde, R.; Ortenberg, R.; Ondrechen, M. J.; Campbell, R. K.; Pollastri, M. P. Pharmacological Validation of Trypanosoma brucei Phosphodiesterases B1 and B2 as Druggable Targets for African Sleeping Sickness. J. Med. Chem. 2011 54, 8188-8194. Diaz-Gonzalez, R.; Kuhlmann, F.M.; Galan-Rodriguez, C.; Madeira da Silva,L.; Karver, C.E.; Beverley, S.M.; Rodriguez, A.; Navarro, M; Pollastri, M.P. “The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing.” PLoS-Neglected Tropical Diseases 2011, 5, e1297