Research Synopsis

Developing novel chemical probes and technologies to study lipid signaling pathways that are involved in development and diseases.

Profile

The Zhang lab studies lipid signaling pathways that are involved in development and diseases by developing novel chemical probes and technologies. As key components of cellular membranes, lipids also serve as signaling molecules and modify functions of proteins through either covalent or non-covalent interactions. Dys-regulation of lipid signaling has been correlated with various diseases including cancer, diabetes, and neurodegenerative diseases. Consequently, many lipid-related proteins or processes have been used as therapeutic targets. However, lipids are dynamically metabolized and transported, making it difficult to illustrate the roles of lipids in development and diseases with limited availability of probes and technologies for lipid studies.

The active projects in the lab include

1. developing novel technologies to synthesize complex lipids, particularly phosphatidylinositides, and to identify their interacting proteins in live cells;
2. developing new small-molecule sensors and inhibitors for lipid metabolic enzymes such as PI3K and PLC; and
3. investigating cellular functions of lipids on different processes, particularly those regulated by small GTPases.

Recent Publications

1. Design, synthesis, and incorporation of fluorous 5-methylcytosines into oligonucleotides. Song Z, Zhang Q. J Org Chem. 2011 Dec 16;76(24):10263-8. Epub 2011 Nov 22. PMID: 22082055 [PubMed - in process]

2. High-Throughput Fluorescence Polarization Assay for the Enzymatic Activity of GTPase-Activating Protein of ADP-Ribosylation Factor (ARFGAP). Sun W, Vanhooke JL, Sondek J, Zhang Q. J Biomol Screen. 2011 Aug;16(7):717-23. Epub 2011 May 18.
PMID: 21593484

3. Kinetic analysis of PI3K reactions with fluorescent PIP(2) derivatives. Huang W, Jiang D, Wang X, Wang K, Sims CE, Allbritton NL, Zhang Q. Anal Bioanal Chem. 2011, 410, 1881-8. Epub 2011 Jul 26.
PMID: 21789487

4. A fluorogenic, small molecule reporter for mammalian phospholipase C isozymes. Huang W, Hicks SN, Sondek J, Zhang Q. ACS Chem Biol. 2011 Mar 18;6(3):223-8. Epub 2011 Jan 10.
PMID: 21158426

5. Chemoenzymatic design of heparan sulfate oligosaccharides. Liu R, Xu Y, Chen M, Weïwer M, Zhou X, Bridges AS, DeAngelis PL, Zhang Q, Linhardt RJ, Liu J. J Biol Chem. 2010 Oct 29;285(44):34240-9. Epub 2010 Aug 21. PMID: 20729556

6. Fluorous aryldiazirine photoaffinity labeling reagents. Song Z, Zhang Q. Org Lett. 2009 Nov 5;11(21):4882-5. PMID: 19807115

7. Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity. Jones CA, Nishiya N, London NR, Zhu W, Sorensen LK, Chan AC, Lim CJ, Chen H, Zhang Q, Schultz PG, Hayallah AM, Thomas KR, Famulok M, Zhang K, Ginsberg MH, Li DY. Nat Cell Biol. 2009 Nov;11(11):1325-31. Epub 2009 Oct 18. PMID: 19855388

8. Reversine increases the plasticity of lineage-committed mammalian cells. Chen S, Takanashi S, Zhang Q, Xiong W, Zhu S, Peters EC, Ding S, Schultz PG. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10482-7. Epub 2007 Jun 12. PMID: 17566101

9. Small-molecule synergist of the Wnt/beta-catenin signaling pathway. Zhang Q, Major MB, Takanashi S, Camp ND, Nishiya N, Peters EC, Ginsberg MH, Jian X, Randazzo PA, Schultz PG, Moon RT, Ding S. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7444-8. Epub 2007 Apr 25
PMID: 17460038

10. Self-renewal of embryonic stem cells by a small molecule. Chen S, Do JT, Zhang Q, Yao S, Yan F, Scholer H, Schultz PG, Ding S. Proc Natl Acad Sci U S A. 2006, Nov 14; 103(46): 17266–17271. Epub 2006 Nov 6. PMID: 17088537