The research lab of Thomas D. Hurley is working 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 the laboratory are X-ray crystallography, inhibitor screening, detailed enzyme kinetics and mass spectrometry.
1R21CA198409-01 (Hurley and Matei, MPI)
Targeting Ovarian Cancer Stem Cells through Selective Inhibition of ALDH1A1
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
Maile, C.A., Hingst, J. R., Mahalingan, K. K., O’Reilly, A. O., Cleasby, M. E., Mickelson, J. R., McCue, M. E., Anderson, S. M., Hurley, T. D., Wojtaszewski, J. F. P., Piercy, R. J. (2016) A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase. Biochim Biophys Acta. 2017 Jan;1861(1 Pt A):3388-3398. doi: 10.1016/j.bbagen.2016.08.021. PMCID: PMC5148651
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
Li, J., Condello, S., Thomas-Pepin, J., Ma, X., Xia, Y., Hurley, T.D., Matei, D. and Cheng, J.-X. (2017) Lipid desaturation is a metabolic marker and therapeutic target of cancer stem cells. Cell Stem Cell, http://dx.doi.org/10.1016/j.stem.2016.11.004. PMCID: PMC5337165
Morgan, CA and Hurley, TD. (2015) Characterization of two distinct structural classes of selective aldehyde dehydrogenase 1A1 inhibitors. J. Med. Chem. 58(4):1964-75. doi: 10.1021/jm501900s. Epub 2015 Feb 10. PMCID: PMC4344389.
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).