Photo of Thomas Bell holding a chemical model.

Thomas W. Bell

Professor

Summary

Research interests

The Bell research group specializes in medicinal chemistry using tools including organic synthesis, molecular modeling, analytical chemistry and molecular biology. Our recent and current projects include muscle myosin inhibitors, male contraceptives, and nascent protein degraders. The last project, which is our major research effort, began in the 1990s with our synthesis of CADA and discovery of its anti-HIV activity. It inhibits entry of HIV into human cells by decreasing expression of CD4, the cell-surface receptor required for infection. CADA targets the nascent CD4 protein chain during translation and diverts it for degradation. We recently found that different CADA analogs selectively degrade other proteins of medicinal interest, leading to our current studies on developing drugs for treating cancer, Graves’ disease, substance use disorder, preterm labor, malaria, and infections by viruses including SARS CoV-2, hepatitis B, dengue, and zika.

Awards

  • National Institutes of Health Postdoctoral Fellow (1980-1982)
  • Fellow of the American Association for the Advancement of Science (1995-present)
  • Plaque of Appreciation from the Korean Chemical Society (2002)
  • College of Science Senior Scholar Mentor, University of Nevada, Reno (2006)
  • College of Science Westfall Scholar Mentor, , University of Nevada, Reno (2016)
  • Foundation Established Innovator Award, University of Nevada, Reno (2018)
  • Outstanding Researcher Award, University of Nevada, Reno (2021)

Education

  • NIH Postdoctoral Fellow, Cornell University (J. Meinwald), 1980-1982
  • Ph.D., University College, University of London (F. Sondheimer), 1980
  • B.S., California Institute of Technology, 1974

Selected publications

  • “Isoform Selectivities of Novel 4-Hydroxycoumarin Imines as Inhibitors of Myosin II” J.D. Smith, J. Brawley, K.C. Bordenave, R.K. Olsen, A. Intasiri, C.R. Cremo, T.W. Bell, Eur. J. Med. Chem. 2023, 247, 115008.
  • “Phenylbutyrate Rescues the Transport Defect of the Sec61α Mutations V67G and T185A for Renin” M. Sicking, M, Živná, P. Bhadra, V. Barešová, A. Tirincsi, D. Hadzibeganovic, K. Hodaňová, P. Vyleťal, J. Sovová, I. Jedličkova, M. Jung, T.W. Bell, V. Helms, Bleyer, A.J, S. Kmoch, A.  Cavalié, S. Lang, Life Science Alliance 2022, 5, e202101150.
  • “Reduction of Progranulin-Induced Breast Cancer Stem Cell Propagation by Sortilin-Targeting Cyclotriazadisulfonamide (CADA) Compounds” K. Berger, E. Pauwels, G. Parkinson, G. Landberg, T. Le, V.G. Demillo, L.A. Lumangtad, D.E. Jones, M.A. Islam, R. Olsen, T. Kapri, A. Intasiri, K. Vermeire, S. Rhost, T.W. Bell, J. Med. Chem. 2021, 64, 12865−12876.
  •  “Syntheses and Anti-HIV and Human Cluster of Differentiation 4 (CD4) Down-modulating Potencies of Pyridine-fused Cyclotriazadisulfonamide (CADA) Compounds” L.A. Lumangtad, E. Claeys, S. Hamal, A. Intasiri, C. Basrai, E. Yen-Pon, D. Beenfeldt, K. Vermeire, T.W. Bell, Bioorg. Med. Chem. 2020, 115816.
  • “Synthesis and Evaluation of 4‐Hydroxycoumarin Imines as Inhibitors of Class II Myosins” J. Brawley, E. Etter, D, Heredia, A. Intasiri, K. Nennecker, J. Smith, B.M. Welcome, R.K. Brizendine, T.W. Gould, T.W. Bell, C. Cremo, J. Med. Chem. 2020, 63, 11131-11148.
  • “The Signal Peptide as a New Target for Drug Design” L. Lumangtad and T.W. Bell, Bioorg. Med. Chem. Lett. 2020, 30, 127115.
  • “Preprotein Signature for Full Susceptibility to the Co-translational Translocation Inhibitor Cyclotriazadisulfonamide”  V. Van Puyenbroeck, E. Pauwels, B. Provinciael, T.W. Bell, D. Schols, K.U. Kalies, E. Hartmann, K. Vermeire, Traffic (Copenhagen, Denmark), 2019, 1-15.
  • “Tsuji-Trost Macrocyclization of Disulfonamides; Synthesis of 12-Membered, 11-Membered, and Pyridine-fused Macrocyclic Triamines” R. Ali, S. Anugu, R. Chawla, V.G. Demillo, F. Goulinet-Mateo, S. Gyawali, S. Hamal, D.E. Jones, K. Lamprecht, T. Le, L.A. Lumangtad, N.C. Pflug, A. Sama, E.D. Scarbrough, and T.W. Bell, ACS Omega 2019, 4, 1254-1264.
  • “A Proteomic Survey Indicates Sortilin as a Secondary Suubstrate of the ER Translocation Inhibitor Cyclotriazadisulfonamide (CADA), V. Van Puyenbroeck, E. Claeys, D. Schols, T.W. Bell, and K. Vermeire, Mol. Cell. Proteomics 2017, 16, 157-167.
  • “Tuning Side Arm Electronics in Unsymmetrical Cyclotriazadisulfonamide (CADA) Endoplasmic Reticulum (ER) Translocation Inhibitors to Improve their Human Cluster of Differentiation 4 (CD4) Receptor Down-Modulating Potencies,” R. Chawla, V. Van Puyenbroeck, N.C. Pflug, A. Sama, R. Ali, D. Schols, K. Vermeire, and T.W. Bell. J. Med. Chem. 2016, 59, 2633-2647.
  • “Metal complexes of pyridine-fused macrocyclic polyamines targeting the chemokine receptor CXCR4,” S. Hamal, T. D’huys, W.F. Rowley, K. Vermeire, S. Aquaro, B.J. Frost, D. Schols, and T.W. Bell, Org. Biomol. Chem. 2015, 13, 10517-10526.
  • “Signal Peptide-Binding Drug as a Selective Inhibitor of Co-Translational Protein Translocation,” K.Vermeire, T.W. Bell,V. Van Puyenbroeck, A. Giraut, S. Noppen, S. Liekens, D. Schols, E. Hartmann, K.-U. Kalies, and M. Marsh, PLOS Biology, 2014.
  • “Improving Potencies and Properties of CD4 Down-Modulating CADA analogs,” T.W. Bell, Expert Opin. Drug Design 2012, 7, 39-48.
  • “Unsymmetrical Cyclotriazadisulfonamide (CADA) Compounds as Human CD4 Receptor Down-Modulating Agents,” V.G. Demillo, F. Goulinet-Mateo, J. Kim, D. Schols, K. Vermeire, and T.W. Bell, J. Med. Chem. 2011, 54, 5712-5721.
  • “Differential Activity of Candidate Microbicides Against Early Steps of HIV-1 Infection upon Complement Virus Opsonization,” M.-A. Jenabian, H. Saïdi, C. Charpentier, H. Bouhlal, D. Schols, J. Balzarini, T. W. Bell, G. Vanham, and L. Bélec, AIDS Research and Therapy 2010, 7, 16-23.
  • “Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility,” K. Vermeire, K. Van Laethem, W. Janssens, T.W. Bell, and D. Schols, J. Virology 2009, 83, 9577-9583.
  • “CADA, a Potential Anti-HIV Microbicide that Specifically Targets the Cellular CD4 Receptor,” K. Vermeire, J. Brouwers, Y. Van Herrewege, R. Le Grand, G. Vanham, P. Augustijns, T. W. Bell, and D. Schols, Current HIV Research 2008, 6, 246-256.
  • “Design and Cellular Kinetics of Dansyl-Labeled CADA Derivatives with Anti-HIV and CD4 Receptor Down-Modulating Activity,” K. Vermeire, A. Lisco, J.C. Grivel, E. Scarbrough, K. Dey, N. Duffy, L. Margolis, T.W. Bell, and D. Schols, Biochemical Pharmacology, 2007, 74, 566-578.
  • “CD4-Targeted HIV Inhibitors,” K. Vermeire, D. Schols, and T.W. Bell, Curr. Med. Chem.,” 2006, 13, 731-743.
  • “Synthesis and Structure-Activity Relationship Studies of CD4 Down-Modulating Cyclotriazadisulfonamide (CADA) Analogs,” T.W. Bell, S. Anugu, P. Bailey, V.J. Catalano, K. Dey, M.G.B. Drew, N.H. Duffy, Q. Jin, M.F. Samala, A. Sodoma, W.H. Welch, D. Schols, and K. Vermeire, J. Med. Chem. 2006, 49, 1291-1312.
  • “CADA, a Novel CD4-Targeted HIV Inhibitor, is Synergistic with Various Anti-HIV Drugs In Vitro,” K. Vermeire, K. Princen, S. Hatse, E. De Clercq,  K. Dey, T.W. Bell and D. Schols, AIDS, 2004, 18, 2115-2125.
  • “CD4 Down-Modulating Compounds with Potent Anti-HIV Activity,” K. Vermeire, D. Schols, and T.W. Bell, Curr. Pharmaceut. Design, 2004, 10, 1795-1803.
  • “The Anti-HIV Potency of CADA Analogues is Directly Correlated with Their Ability to Down-Modulate the CD4 Receptor,” K. Vermeire, T.W. Bell, H.-J. Choi, Q. Jin, M.F. Samala, A. Sodoma, E. de Clercq, and D. Schols, Mol. Pharmacol. 2003, 63, 203-210.
  • “CADA Inhibits Human Immunodeficiency Virus and Human Herpesvirus 7 Replication by Down-modulation of the Cellular CD4 Receptor,” K. Vermeire, Y. Zhang, K. Princen, S. Hatse, M. Samala, K. Dey, H.-J. Choi, Y. Ahn, A. Sodoma, R. Snoeck, G. Andrei, E. de Clercq, T.W. Bell, and D. Schols, Virology 2002, 302, 342-353.