Paul Carlier

Professor

Organic and Medicinal Chemistry

Research Interests:
Medicinal Chemistry and Chemistry for Global Health. Malaria is a scourge in the developing world, affecting 200 million people and killing nearly 450,000 annually. We are taking a two-pronged strategy to reduce malaria transmission and mortality. Firstly, new antimalarial drugs are urgently needed to treat infected individuals, and we are working with Prof. Dan Slade (Biochemistry), Prof. Cassera (Univ. Georgia), and Dr. Totrov (Molsoft LLC) to develop a new class of antimalarial drug that targets isoprenoid biosynthesis in the parasite. A second aspect of our research involves development of new human safe insecticides to reduce disease transmission by Malaria mosquitoes.

Enantioselective Synthetic Methods. Organolithium and organomagnesium reagents are ubiquitous in organic synthesis. We are interested in developing new stereoselective reactions of group 1 and 2 organometallics and enolates, and in using computation and kinetic methods spectroscopy to determine structures and reaction pathways. The methods we develop aim to provide drug-like molecules in enantiomerically pure form. Our overall goal is to provide medicinal chemists with new tools to advance drug discovery.

  1. “Crystal structure of the G119S mutant acetylcholinesterase of the malaria vector An. gambiae reveals the basis of insecticide resistance” Jonah Cheung*, Arshod Mahmood, Ravi Kalathur, Lixuan Liu, Paul R. Carlier, Structure 2018126, 130-136, PMID: 29276037, DOI:10.1016/j.str.2017.11.021
  2. Select β- and 𝛾-branched 1-alkylpyrazol-4-yl methylcarbamates exhibit high selectivity for inhibition of Anopheles gambiae versushuman acetylcholinesterase. Paul R. Carlier*, Qiao-Hong Chen, Astha Verma, Dawn M. Wong, James M. Mutunga, Jasmin Müller, Alex M. Shimozono, Rafique Islam, Fan Tong,Jianyong Li, Max Totrov,Jeffrey R. Bloomquist, Pesticide Biochemistry and Physiology, 2018, in press, https://doi.org/10.1016/j.pestbp.2018.02.003
  3. Biological studies and target-engagement of the 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD)-targeting antimalarial agent (1R,3S)-MMV008138 and analogs. Maryam Ghavami, Emilio F. Merino, Zhong-Ke Yao, Rubayat Elahi, Morgan E. Simpson, Maria L. Fernandez-Murga, Joshua H. Butler, Michael A. Casasanta, Priscilla M. Krai, Maxim M. Totrov, Daniel J. Slade, Paul R. Carlier*, and Maria Belen Cassera*, ACS Infectious Diseases 20184, 549-559. PMID: 29072835, 
    DOI: 10.1021/acsinfecdis.7b00159
  4. Discovery of Species-selective and Resistance-breeaking Anticholinesterase Insecticides for the Malaria Mosquito. Paul R. Carlier*, Jeffrey R. Bloomquist, Max Totrov, and Jianyong Li, invited review, Current Medicinal Chemistry 2017, 24, 2946–2958. DOI: 10.2174/0929867324666170206130024
  5. N'-Mono- and N,N'-diacyl derivatives of benzyl and arylhydrazines as contact insecticides against adult Anopheles gambiae. Joseph S. Celements II, Fan Tong, Baonan Sun, Aaron d. Gross, Rafique Islam, Jeffrey R. Bloomquistb, Paul R. Carlier*, Pesticide Biochemistry and Physiology 2017, 143, 33–38, DOI: 10.1016/j.pestbp.2017.10.001
  6. Parallel inhibition of amino acid efflux and parasite growth of erythrocytic Plasmodium falciparum by mefloquine and non-piperidine analogs: implications for the mechanism of antimalarial action Maryam Ghavami, Christine Dapper, Seema Dalal, Kristina Holzschneider, Michael Klemba, and Paul R. Carlier*, Bioorganic & Medicinal Chemistry Letters 2016, 26, 4846-4850, DOI: 10.1016/j.bmcl.2016.08.005
  • North America Regional Editor, Current Topics in Medicinal Chemistry, 2015–present
  • Member, International Advisory Board, Cholinergic Mechanisms Meeting, 2013 to present
  • Jimmy Viers Teaching Award, Department of Chemistry, Virginia Tech, 2017
  • Scholar of the Week, June 2013, Office of the VP for Research, Virginia Tech
  • Cook Faculty Research Award, VT Chemistry, 2006
  • Hamilton College Alumni Achievement Medal, 2005
  • B.S. Hamilton College, 1983
  • Ph.D. Massachusetts Institute of Technology, 1988
  • Scientist, Polaroid Corporation, 1988–1991
  • Assistant to Associate Professor of Chemistry, Hong Kong University of Science of Technology, 1991–2000
  • Associate Professor of Chemistry, 2000–2007
  • Professor of Chemistry, Virginia Teh, 2007–present
  • Deputy Director, Virginia Tech Center for Drug Discovery
  • Executive Committe Member, Virginia Drug Discovery Consortium
Professor Paul Carlier

Contact

Email: pcarlier@vt.edu
Office: 3103 Hahn Hall South
Phone: 540-231-9219
Group Website: http://www.carlierlab.com

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