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Research: Rho GTPases, Dbl-family RhoGEFs, Phospholipase C isozymes, Drug discovery

Professor of Pharmacology, UNC-CH
Joint Appointment in Biochemistry and Biophysics
PhD – Johns Hopkins University

Trained Faculty Mentor endorsed by Office of Graduate Ed UNC Chapel Hill


  • 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



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.


Link to all Pubs


Dynamics of allosteric regulation of the phospholipase C-γ isozymes upon recruitment to membranes.
Siraliev-Perez E, Stariha JTB, Hoffmann RM, Temple BRS, Zhang Q, Hajicek N, Jenkins ML, Burke JE, Sondek J. Elife. 2022 Jun 16;11:e77809. doi: 10.7554/eLife.77809. PMID: 35708309 Free PMC article.

Designer proteins that competitively inhibit Gαq by targeting its effector site.
Hussain M, Cummins MC, Endo-Streeter S, Sondek J, Kuhlman B. J Biol Chem. 2021 Dec;297(6):101348. doi: 10.1016/j.jbc.2021.101348. Epub 2021 Oct 27. PMID: 34715131 Free PMC article.

Fluorogenic XY-69 in Lipid Vesicles for Measuring Activity of Phospholipase C Isozymes.
Carr AJ, Siraliev-Perez E, Huang W, Sondek J, Zhang Q. Methods Mol Biol. 2021;2251:225-236. doi: 10.1007/978-1-0716-1142-5_17. PMID: 33481244 Free PMC article.

A High-Throughput Assay to Identify Allosteric Inhibitors of the PLC-γ Isozymes Operating at Membranes.
Huang W, Carr AJ, Hajicek N, Sokolovski M, Siraliev-Perez E, Hardy PB, Pearce KH, Sondek J, Zhang Q. Biochemistry. 2020 Oct 20;59(41):4029-4038. doi: 10.1021/acs.biochem.0c00511. Epub 2020 Oct 7. PMID: 33028071 Free PMC article.

Multiplexed GTPase and GEF biosensor imaging enables network connectivity analysis.
Marston DJ, Vilela M, Huh J, Ren J, Azoitei ML, Glekas G, Danuser G, Sondek J, Hahn KM. Nat Chem Biol. 2020 Aug;16(8):826-833. doi: 10.1038/s41589-020-0542-9. Epub 2020 May 18. PMID: 32424303 Free PMC article.

Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations.
Hajicek N, Keith NC, Siraliev-Perez E, Temple BR, Huang W, Zhang Q, Harden TK, Sondek J. Elife. 2019 Dec 31;8:e51700. doi: 10.7554/eLife.51700. PMID: 31889510 Free PMC article.

Spatiotemporal dynamics of GEF-H1 activation controlled by microtubule- and Src-mediated pathways.
Azoitei ML, Noh J, Marston DJ, Roudot P, Marshall CB, Daugird TA, Lisanza SL, Sandí MJ, Ikura M, Sondek J, Rottapel R, Hahn KM, Danuser G. J Cell Biol. 2019 Sep 2;218(9):3077-3097. doi: 10.1083/jcb.201812073. Epub 2019 Aug 16. PMID: 31420453 Free PMC article.

Calcium-induced structural rearrangements release autoinhibition in the Rap-GEF CalDAG-GEFI.
Cook AA, Deng W, Ren J, Li R, Sondek J, Bergmeier W. J Biol Chem. 2018 Jun 1;293(22):8521-8529. doi: 10.1074/jbc.RA118.002712. Epub 2018 Apr 5. PMID: 29622678 Free PMC article.

A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes.
Huang W, Wang X, Endo-Streeter S, Barrett M, Waybright J, Wohlfeld C, Hajicek N, Harden TK, Sondek J, Zhang Q. J Biol Chem. 2018 Feb 2;293(5):1728-1735. doi: 10.1074/jbc.RA117.000926. Epub 2017 Dec 20. PMID: 29263090 Free PMC article.

TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death in Arabidopsis.
Nishimura MT, Anderson RG, Cherkis KA, Law TF, Liu QL, Machius M, Nimchuk ZL, Yang L, Chung EH, El Kasmi F, Hyunh M, Osborne Nishimura E, Sondek JE, Dangl JL. Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):E2053-E2062. doi: 10.1073/pnas.1620973114. Epub 2017 Jan 30. PMID: 28137883 Free PMC article.

Lab Contact:

Lab Rooms: 4060 Genetic Medicine

Lab Fax: 919-966-5640

John Sondek
  • Phone Number

    919-966-7530 (Office Phone)

  • Address

    120 Mason Farm Road, CB# 7260

    4060 Genetic Medicine

    Chapel Hill, NC 27599-7260