Thomas W. Bell

Summary

Thomas W. Bell is a Professor of Chemistry at the University of Nevada, Reno. He obtained a B.S. degree with honors from California Institute of Technology in 1974 then received his Ph.D. in Organic Chemistry from University College, London in 1980, having conducted his thesis research with Franz Sondheimer (UCL) and Donald J. Cram (UCLA). He worked with Jerrold Meinwald as an NIH Postdoctoral Fellow at Cornell University, then he joined the State University of New York at Stony Brook as an Assistant Professor in 1982. There, he reached the rank of Professor in 1991, then moved to his current position at the University of Nevada, Reno in 1995. He has been Fellow of the American Association of the Advancement of Science since 1994. In 1990 and 1996 he was a Visiting Professor at Université Louis Pasteur in Strasbourg, France, and for the 2015-2016 academic year he was a Visiting Professor at the University of Leuven (KU Leuven) in Belgium. He won the University of Nevada, Reno's Foundation Established Innovator award in 2018 and the Outstanding Researcher award in 2021.

Bell’s research interests over his entire academic career have included supramolecular chemistry, chemosensors, advanced materials, nanoscale molecular assemblies and devices, and medicinal chemistry. His current research interests in synthetic organic and medicinal chemistry center on developing drugs that recognize nascent proteins and cause their intracellular degradation. Nascent protein degraders bind the signal peptides or first transmembrane domains of target proteins and inhibit their expression by decreasing their translocation across the ER membrane through the Sec61 channel. The Bell research group is collaborating with many research groups in the USA and around the world to validate this novel drug target by designing and testing drugs for treating cancer, viral infections (HIV, SARS-CoV-2, dengue, zika, and hepatitis B), malaria, Graves’ disease, neurodegenerative diseases (Alzheimers, opioid use disorder), rheumatoid arthritis, neurodegenerative diseases and preterm labor.

He currently has more than 130 publications in scientific journals and is inventor or co-inventor on 11 patents. His recreational interests include hiking, backpacking, rock climbing, mountain biking, skiing, snowboarding and Scuba diving.

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.

Honors and awards

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

News features

• Moving closer to “one protein, one drug"

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

• Xu, X.; Bell, T.; Le, T.; Zhao, I.; Walker, E.; Wang, Y.; Xu, N.; Soleimanpour, S. A.; Russ, H. A.; Qi, L.; Tsai, B.; Liu, M.; Arvan, P. Role of Sec61a2 Translocon in Insulin Biosynthesis. Diabetes 2024, 73, 2034-2044.
• Intasiri, A.; Illa, S. E.; Prertprawnon, S.; Wang, S.; Li, L.; Bell, T. W.; Li, D. Comparison of in vitro membrane permeabilities of diverse environmental chemicals with in silico predictions. Science of the Total Environment 2024, 933, 173244.
• Smith, J. D.; Brawley, J.; Bordenave, K. C.; Olsen, R. K.; Intasiri, A.; Cremo, C. R.; Bell, T. W. Isoform selectivities of novel 4-hydroxycoumarin imines as inhibitors of myosin II. J. Med. Chem. 2023, 247, 115008.
• Sicking, M.; Živná, M.; Bhadra, P.; Barešová, V.; Tirinsci, A.; Hadzibeganovic, D.; Hodaňová, K.; Vyleťal, P.; Sovová, J.; Jedličkova, I.; Jung, M.; Bell, T. W.; Helms, V.; Bleyer, A. J.; Kmoch, S.; Cavalié, A.; Lang, S. Phenylbutyrate Rescues the Transport Defect of the Sec61α Mutations V67G and T185A for Renin. Life Science Alliance 2022, 5,
• Berger, K.; Pauwels, E.; Parkinson, G.; Landberg, G.; Le, T.; Demillo, V. G.; Lumangtad, L. A.; Jones, D. E.; Islam, M. A.; Olsen, R.; Kapri, T.; Intasiri, A.; Vermeire, K.; Rhost, S.; Bell, T. W. Reduction of Progranulin-Induced Breast Cancer Stem Cell Propagation by Sortilin-Targeting Cyclotrazadisulfonamide (CADA) Compounds. Med. Chem. 2021, 64, 12865-12876.
• Lumangtad, L. A.; Claeys, E.; Hamal, S.; Intasiri, A.; Basrai, C.; Yen-Pon, E.; Beenfeldt, D.; Vermeire, K.; Bell, T. W. Syntheses and Anti-HIV and Human Cluster of Differentiation 4 (CD4) Down-modulating Potencies of Pyridine-fused Cyclotriazadisulfonamide (CADA) Compounds. Med. Chem. 2020, 115816.
• Brawley, J.; Etter, E.; Heredia, D.; Intaasiri, A.; Nennecker, K.; Smith, J.; Welcome, B. M.; Brizendine, R. K.; Gould, T. W.; Bell, T. W.; Cremo, C. Synthesis and Evaluation of 4-Hydroxycoumarin Imines as Inhibitors of Class II Myosins. Med. Chem. 2020, 63, 11131-11148.
• Lumangtad, L.; Bell, T. W. The Signal Peptide as a New Target for Drug Design. Med. Chem. Lett. 2020, 30, 127115.