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Research Interests:
Our lab is interested in identifying functional small molecules from synthetic and endogenous chemical libraries and studying how these molecules regulate disease-related cell signaling. Other than traditional methods in chemical synthesis, molecular and cell biology and the emerging technique of high throughput screening, we also develop new techniques of tag-based biosynthesis and enzyme profiling, as well as small molecule array, to facilitate research. Currently, we are working on the following three projects:
1) Chemical approaches to probe Phosphatidylinositide-regulated cellular processes. Phosphatidylinositides (PIs) are a family of anchoring lipids with different combinations of phosphate groups around the inositol ring. Due to their functions of membrane recruitment and activation of downstream effector proteins, PIs are among the most versatile endogenous regulatory small molecules. Dys-regulation of PI signaling has been implicated in diseases such as Low syndrome, cancer, and myotubular myopathy. We are generating an array of natural and unnatural PIs to systematically identify PI-interacting proteins for novel drug target discovery and disease diagnosis. In addition, we are developing small molecules that inhibit enzymes that control PI metabolism.
2) Developing small molecule ARFGAP inhibitors to dissect cell signaling. GTPase-activating proteins for the ADP-ribosylation factors (ARFGAPs) play important roles in many biological processes, including vesicle trafficking and cytoskeleton reorganization. Recently, we identified a small molecule ARFGAP inhibitor from a high throughput chemical screen. We are exploring the functions and mode of actions of this molecule in membrane trafficking, cell migration, and neurite outgrowth.
3) Cellular epigenetic status controlled by DNA demethylation and histone methylation. Changes in Cellular epigenetic status are essential for cellular differentiation and reprogramming, and thus regenerative medicine. We are developing methods to profile DNA demethylation and develop small molecules that inhibit histone methyltransferases.

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Publications

1.      Yu, H.; Zhang, Q.; Huang, W. A Two-step Approach to 2-Polyfluoroalkyl Quinolines from N-aryl Polyfluoroalkyl Imidoyl Iodides. Chinese Journal of Chemistry 1997, 15, 278–282.

2.      Zhang, Q.; Lu, L. A Novel Synthetic Route to Ethyl 3-Substituted-trans-2,3-difluoro-2-acrylates and Their Reactions with Nucleophiles. Tetrahedron Letters 2000, 41, 8545–8548.

3.      Zhang, Q.; Luo, Z.; Curran, D. P. Separation of “Light Fluorous” Reagents and Catalysts by Fluorous Solid-Phase Extraction: Synthesis and Study of a Family of Triarylphosphines Bearing Linear and Branched Fluorous Tags. Journal of Organic Chemistry 2000, 65, 8866–8873.

4.      Luo, Z.; Zhang, Q.; Oderaotoshi, Y.; Curran, D. P. Fluorous Mixture Synthesis: A Fluorous-Tagging Strategy for the Synthesis and Separation of Mixtures of Organic Compounds. Science 2001, 291, 1766–1769.

5.      Zhang, Q.; Rivkin, A.; Curran, D. P. Quasiracemic Synthesis: Concepts and Implementation with a Fluorous Tagging Strategy to Make Both Enantiomers of Pyridovericin and Mappicine. Journal of the American Chemical Society 2002, 124, 5774–5781.

6.      Curran, D. P.; Zhang, Q. Microwave Heating Effects Rapid and Selective Decarboalkoxylation of Mono-Alkylated Malonates and -Ketoesters. Advanced Synthesis & Catalysis 2003, 345, 329–333.

7.      Vallin, K. S. A.; Zhang, Q.; Larhed, M.; Curran, D. P.; Hallberg, A. A New Regioselective Heck-Vinylation with Enamides: Synthesis and Investigation of Fluorous-Tagged Bidentate Ligands for Fast Separation. Journal of Organic Chemistry 2003, 68, 6639–6645.

8.      Chen, S.; Zhang, Q.; Wu, X.; Schultz, P. G.; Ding, S. Cellular Dedifferentiation of Lineage-Committed Myogenic Cells Induced by Reversine. Journal of the American Chemical Society 2004, 126, 410–411.

9.      Zhang, Q.; Lu, H.; Richard, C. R.; Curran, D. P. Synthesis of Sixteen Stereoisomers of Murisolin, Murisolin A and 16,19-cis-Murisolin by Fluorous Mixture Synthesis. Journal of the American Chemical Society 2004, 126, 36–37.

10.  Curran, D. P.; Wang, X.; Zhang, Q. Heavy, Medium and Light Fluorous Triarylphosphines Exhibit Comparable Reactivities to Triphenylphosphine in Typical Reactions of Triarylphosphines. Journal of Organic Chemistry 2005, 70, 3716–3719.

11.  Zhang, Q.; Curran, D. P. Quasienantiomers and Quasiracemates: New Tools for Identification, Analysis, Separation and Synthesis of Quasienantiomers.  Chemistry- A European Journal 2005, 11, 4866–4880.

12.  Curran, D. P.; Zhang, Q.; Lu, H.; Gudipati, V. On the Proof and Disproof of Natural Product Stereostructures: Characterization and Analysis of a Twenty-Eight Member Stereoisomer Library of Murisolins and Their Mosher Ester Derivatives. Journal of the American Chemical Society, 2006, 128, 9943–9956.

13.  Curran, D. P.; Zhang, Q.; Richard, C. R.; Lu, H.; Gudipati, V. Total Synthesis of a Twenty-eight Member Stereoisomer Library of Murisolins. Journal of the American Chemical Society, 2006, 128, 9561–9573.

14.  Chen, S.; Do, J.; Zhang, Q.; Yao, S.; Yan, F.; Scholer, H. Schultz, P. G.; Ding, S. Maintenance of human and mouse embryonic stem cells self-renewal by a small molecule. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103, 17266–17271.

15.  Zhang, Q.; Major, B.; Takanashi, S.; Camp, N. D.; Nishiya, N.; Peters, E. C.; Ginsberg, M.; Schultz, P. G.; Moon, R. T.; Ding, S. A Small Molecule Synergist of the Wnt/β-catenin Signaling Pathway. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104, 7444–7448.

16.  Chen, S.; Takanashi, S.; Zhang, Q.; Xiong, W.; Peters, E.C.; Ding, S.; Schultz, P.G. Reversine Induces Cellular Reprogramming of Lineage-Committed Mammalian Cells. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104, 10482-10487.

17.     Song, Z. and Zhang, Q. “Fluorous Aryl Diazirine Photoaffinity Labeling Reagents”, Organic Letters 2009, 11, 4882-4885.     

18.     Jones, C. A.; Nishiya, N.; London, N. R.; Zhu, W.; Sorensen, L. K.; Chan, A.; Lim, C. J.; Chen, H.; Zhang, Q.; Schultz, P. G.; Hayallah, A. M.; Thomas, K. R.; Famulok, M.; Zhang, K.; Ginsberg, M. H.; Li, D. Y. “Slit2-Robo4 Signaling Promotes Vascular Stability by Blocking Arf6 Activity”, Nature Cell Biology 2009, ASAP article.