The major focus of Thomas D. Hurley, PhD‘s research lab is to understand, at the molecular level, the processes involved in the recognition and binding of molecules that are directed to the active sites of enzymes. The main approaches utilized in this laboratory are X-ray crystallography, inhibitor screening, detailed enzyme kinetics and mass spectrometry.
R01DK27221-37 (Roach and Hurley, MPI)
Small Molecule Inhibition of Glycogen Storage as Therapy of Glycogenoses
1R01CA214567-01 (PI: Larson; Hurley- CoI)
Isozyme-selective ALDH Inhibitors for Sensitizing Ovarian Cancer Stem-like Cells to Chemotherapy
P01NS097197-01 Project #3: (Leader: P Roach/Hurley – Co-I)
Suppressing glycogen storage with small molecule inhibitors as a therapeutic approach to LD
Define the clinical biochemistry of LD mutations to provide a personalized diagnosis and establish therapeutic options to treat LD, ultimately resulting in a cure.
Chefetz I, Grimley E, Yang K., Hong L, Vinogradova EV, Suciu R, Kovalenko I, Karnak D, Morgan CA, Chtcherbinine M, Buchman C, Huddle B, Barraza S, Morgan M, Bernstein KA, Yoon ES, Lombard D, Bild A, Mehta G, Romero I, Chiang CY, Landen C, Cravatt B, Hurley TD, Larsen SD, and Buckanovich RJ. (2019) A Pan-ALDH1A Inhibitor Induces Necroptosis in Ovarian Cancer Stem-Like Cells. Cell Reports Mar 12;26(11):3061-3075.e6. doi: 10.1016/j.celrep.2019.02.032.
Sarvi, S., Crispin, R., Lu, Y., Zeng, L., Hurley, T.D., Houston, D.R., von Kriegsheim, A., Chen, C.-H., Mochly-Rosen, D., Ranzani, M., Mathers, M.E., Xu, X., Xu, W., Adams, D.J., Carragher, N.O., Fujita, M., Schuchter, L., Unciti-Broceta, A., Brunton, V.G. and Patton, E.J. (2018) ALDH1 bio-activates nifuroxazide to eradicate ALDH-High melanoma-initiating cells. Cell Chem Biol. 2018 Dec 20;25(12):1456-1469.e6. doi: 10.1016/j.chembiol.2018.09.005. Epub 2018 Oct 4. PMCID: PMC6309505
Huddle, B., Grimley, E., Buchman, C., Chtcherbinine, M., Debnath, B., Mehta, P., Yang, K., Morgan, C., Li, S., Felton, J., Sun, D., Metha, G., Neamati, N., Buckanovich, R., Hurley, T.D., Larsen, S. (2018) Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy Oct 11;61(19):8754-8773. doi: 10.1021/acs.jmedchem.8b00930. Epub 2018 Sep 28. PMCID – in process.
Mahalingan, K.K., Baskaran, S., DePaoli-Roach, A.A., Roach, P.J. and Hurley, T.D. (2017) Redox switch for the inhibited state of yeast glycogen synthase mimics regulation by phosphorylation. Biochemistry 56(1):179-188. doi: 10.1021/acs.biochem.6b00884. Epub 2016 Dec 20. PMCID: PMC5516924
Buchman, C.D. and Hurley, T.D. (2017) Inhibition of the Aldehyde Dehydrogenase 1/2 Family by Psoralen and Coumarin Derivatives. J. Med. Chem. (in press). PMCID: in process
Faculty Research Team
Additional Research Team Members
Other research team members in the Hurley Lab include Bruce Tang (PhD graduate student), Mikhail Chcterbinine (PhD graduate student), and Cyrus Takahashi (MD/PhD graduate student).