Joint Appointment in Biochemistry and Biophysics
ACCEPTING STUDENTS
HONORS
- 2013 Winner, GlaxoSmithKline Discovery Fast Track Competition
- 2011 Chair, Gordon Research Conference
- 2008 Keynote Lecture, SER-CAT symposium
- 1999 Pew Scholar in the Biomedical Sciences
RESEARCH
Summary:
We are focused on understanding signal transduction cascades controlled by heterotrimeric G proteins (Gabg) and small GTPases related to Ras. We primarily use biophysical techniques to dissect these cascades at atomic and molecular resolution in order to understand and manipulate cellular processes. Among other work, we are currently using these studies to guide rational drug design and develop high throughput screens to identify modulators of key signaling components and to produce biosensors to monitor these cascades in real-time in cells.
REPRESENTATIVE PUBLICATIONS
(click for Full Publication List)
- Charpentier, T.H., Waldo, G.L., Barrett, M.O., Huang, W., Zhang, Q., Harden, T.K. and Sondek, J. (2014). Membrane-induced allosteric control of phospholipase C-b isozymes. J. Biol. Chem. 289, 29545-29557. PMCID: PMC4207972.
- Hajicek, N., Charpentier, T.H., Rush, J.R., Harden, T.K. and Sondek, J. (2013). Autoinhibition and phosphorylation-induced activation of phospholipase C- g isozymes. Biochemistry 52, 4810-4819. PMCID: PMC3844103.
- Huang, W., Barrett, M., Hajicek, N., Hicks, S., Harden, T. K., Sondek, J., and Zhang, Q. (2013). Small molecule inhibitors of phospholipase C from a novel high-throughput screen. J. Biol. Chem. 288, 5840-5848. PMCID: PMC3581404.
- Wang, X., Barrett, M., Sondek, J. Harden, T.K. and Zhang, Q. (2012). Fluorescent phosphatidylinositol 4,5-bisphosphate derivatives with modified 6-hydroxy group as novel substrates for phospholipase C. Biochemistry. 51, 5300-5306. PMCID: PMC3603374
- Waldo, G.L., Ricks, T.K., Hicks, S.N., Cheever, M.L., Kawano, T., Tzuboi, K., Wang, X., Montell, C., Kozasa, T., Sondek, J. and Harden, T.K. (2010) Kinetic Scaffolding Mediated by a Phospholipase C-β and Gq Signaling Complex. Science 330: 974-980.
- Gresset A, Hicks SN, Harden TK and Sondek J. (2010) Mechanism of Phosphorylation-induced Activation of Phospholipase C-g Isozymes. J Biol Chem. 285(46):35836-35847.
Lab Contact:
Lab Rooms: 4060 Genetic Medicine
Lab Fax: 919-966-5640