Personal profile
Research Interests
The Hughes lab conducts drug design in collaboration with medicinal chemists. We also investigate how drugs alter the receptors they bind to using various biochemical and biophysical experimental methods, as well as molecular dynamics simulations. We connect these drug-induced biophysical changes with functional outcomes in cell culture (e.g., through measurement of transcription). Our primary methods are multidimensional protein NMR, fluorine NMR, computational simulations, isothermal titration calorimetry, time-resolved FRET, fluorescence polarization, cell culture, and transcriptome analysis. We focus on the nuclear hormone receptor family, which is the molecular target of more than 10% of FDA-approved drugs. Our work improves the biophysical understanding of how drugs produce effects in this family, which aids the development of new therapies with reduced undesired effects. Current work mainly focuses on one member of this family, PPARγ, which binds the prescription anti-diabetes drugs pioglitazone (Actos) and rosiglitazone (Avandia).
Teaching Experience
PHAR 329 (Microbes and Medicines)
BCH 294 (Biochemistry Seminar: Intro to Biochemistry Faculty Research)
BMED 615 (Molecular Pharmacology)
Education/Academic qualification
Bachelor, Physics, Brigham Young University
Master, Physics, Brigham Young University
Doctorate, Molecular, Cellular, and Developmental Biology, University of Colorado Boulder
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
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SDG 3 Good Health and Well-being
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Collaborations and top research areas from the last five years
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MDRepo-an open data warehouse for community-contributed molecular dynamics simulations of proteins
Roy, A., Ward, E., Choi, I., Cosi, M., Edgin, T., Hughes, T. S., Islam, M. S., Khan, A. M., Kolekar, A., Rayl, M., Robinson, I., Sarando, P., Skidmore, E., Swetnam, T. L., Wall, M., Xu, Z., Yung, M. L., Merchant, N. & Wheeler, T. J., Jan 6 2025, In: Nucleic Acids Research. 53, D1, p. D477-D486Research output: Contribution to journal › Article › peer-review
Open Access8 Scopus citations -
Agonists of the Nuclear Receptor PPARg Can Produce Biased Signaling
Rayl, M. L., Nemetchek, M. D., Voss, A. H. & Hughes, T. S., Dec 1 2024, In: Molecular Pharmacology. 106, 6, p. 309-318 10 p.Research output: Contribution to journal › Article › peer-review
Open Access2 Scopus citations -
International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily—Update 2023
Burris, T. P., de Vera, I. M. S., Cote, I., Flaveny, C. A., Wanninayake, U. S., Chatterjee, A., Walker, J. K., Steinauer, N., Zhang, J., Coons, L. A., Korach, K. S., Cain, D. W., Hollenberg, A. N., Webb, P., Forrest, D., Jetten, A. M., Edwards, D. P., Grimm, S. L., Hartig, S. & Lange, C. A. & 16 others, , Nov 1 2023, In: Pharmacological Reviews. 75, 6, p. 1233-1318 86 p.Research output: Contribution to journal › Article › peer-review
Open Access35 Scopus citations -
A structural mechanism of nuclear receptor biased agonism
Nemetchek, M. D., Chrisman, I. M., Rayl, M. L., Voss, A. H. & Hughes, T. S., Dec 13 2022, In: Proceedings of the National Academy of Sciences of the United States of America. 119, 50, e2215333119.Research output: Contribution to journal › Article › peer-review
Open Access23 Scopus citations -
Defining a Canonical Ligand-Binding Pocket in the Orphan Nuclear Receptor Nurr1
de Vera, I. M. S., Munoz-Tello, P., Zheng, J., Dharmarajan, V., Marciano, D. P., Matta-Camacho, E., Giri, P. K., Shang, J., Hughes, T. S., Rance, M., Griffin, P. R. & Kojetin, D. J., Jan 2 2019, In: Structure. 27, 1, p. 66-77.e5Research output: Contribution to journal › Article › peer-review
Open Access44 Scopus citations