研究领域
Photoacoustic Imaging
Photoacoustic (PA) imaging is an emerging modality that is based on the detection of acoustic waves generated by optically excited chromophores. Owing to the low scattering of sound in biological tissues, PA is ideal for non-invasive, deep-tissue bioimaging of live animals and human organs. Our group will develop novel approaches and chemical probes to detect biologically relevant analytes and molecular signaling events using PA imaging. These tools will be applied to explore cancer biology, diagnosis, and treatment.
Infectious Diseases
锘縄nfectious diseases are responsible for more deaths worldwide than any other single cause. For instance, nearly two million people die each year from tuberculosis (TB) infections. However, current TB tests are slow and existing drugs are often ineffective. Drawing from our expertise in mechanistic enzymology, synthetic chemistry, and molecular imaging, we will exploit pathogen-specific enzymatic activities to develop rapid point-of-care diagnostics and targeted therapeutics for TB, as well as for other infectious diseases.
Neurological Disorders
锘� Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by a decline in cognitive abilities that result from neuronal cell death. It is believed that hypoxia, oxidative stress, metal ion signaling, and neurotransmission all play a role in the neuropathology of AD; however, their interplay is inadequately studied, especially in the context of in vivo biological systems. Our group is currently developing chemical and protein-based probes to discover the mechanisms underlying this medical condition
近期论文
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Chan J, Tang A, Bennet AJ. Transition-state structure for the hydronium ion-promoted hydrolysis of 伪-D-glucopyranosyl fluoride. Can J Chem 2014, Just-IN.
Dodani SC,* Firl A,* Chan J,* Nam CI, Aron AT, Onak CS, Ramos-Torres KM, Paek J, Webster CM, Feller MB, Chang CJ. Copper is an endogenous modulator of neural circuit spontaneous activity. PNAS 2014, 111, 16280-1625. [* = equal contribution]
Hong-Hermesdorf A, Miethke M, Gallaher SD, Kropat J, Dodani SC, Chan J, Barupala D, Domaille DW, Shirasaki DI, Loo JA, Weber PK, Pett-Ridge J, Stemmler TL, Chang CJ, Merchant SS. Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas. Nature Chem. Biol. 2014, 10, 1034-1042.
Chan J, Sannikova N, Tang A, Bennet J. Transition-state structure for the quintessential SN2 reaction of a carbohydrate: Reaction of α-glucopyranosyl fluoride with azide ion in water. J. Am. Chem. Soc. 2014, 136, 12225-12228.
Kashyap DR, Rompca A, Gaballa A, Helmann JD, Chan J, Chang CJ, Gupta D, Dziarski R. Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress. PLoS Pathog. 2014, 10, 1-17.
Polishchuk EV, Concilli M, Iacobacci S, Chesi G, Pastore N, Piccolo P, Paladino S, Baldantoni D, van IJzendoorn SCD, Chan J, Chang CJ, Amoresano A, Pane F, Pucci P, Tarallo A, Parenti G, Brunetti-pierri N, Settembre C, Ballabio A, Polishchuck RS. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. Dev. Cell. 2014, 29, 686-700.
Chan J, Chang CJ. Making light of stress. Nature Biotechnol. 2014, 32, 337-338.
Huang CP, Fofana M, Chan J, Chang CJ, Howell SB. Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin. Metallomics 2014, 6, 654-661.
Hao Z, Lou H, Zhu R, Zhu J, Zhang D, Zhao BS, Zeng S, Chen X, Chan J, He C, Chen PR. The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli. Nature Chem. Biol. 2014, 10, 21-28.
Au-Yeung HY, Chan J, Chantarojsiri T, Chang CJ. Molecular imaging of labile iron(II) pools in living cells with a turn-on fluorescent probe. J. Am. Chem. Soc. 2013, 135, 15165-15173.
Chan J, Dodani SC, Chang CJ. Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nature Chem. 2012, 2, 973-984.
Macauley MS, Chan J, Zandberg W, He Y, Whitworth GA, Stubbs KA, Yuzwa SA, Bennet AJ, Varki A, Davies GJ, Vocadlo DJ. Metabolism of vertebrate amino sugars with N-glycolyl groups: Intracellular O-GlcNGc, UDP-GlcNGc, and the biochemical and structural rationale for the substrate tolerance of O-GlcNAcase. J. Biol. Chem. 2012, 287, 28882-28897.
Chan J, Lewis AR, Indurugalla D, Schur M, Wakarchuk W, Bennet AJ. Transition state analysis of Vibrio cholerae sialidase-catalyzed hydrolyses of natural substrate analogues. J. Am. Chem. Soc. 2012, 134, 3748-3757.
Chan J, Tang A, Bennet AJ. A stepwise solvent-promoted SNi reaction of 伪-d-glucopyranosyl fluoride: mechanistic implications for retaining glycosyltransferases. J. Am. Chem. Soc. 2012, 134, 1212-1220.
Chan J, Watson JN, Lu A, Borgford TJ, Bennet AJ. Bacterial and viral sialidases: Contribution of the conserved active site glutamate to catalysis. Biochemistry 2012, 51, 433-441.
Chan J, Bennet AJ. "Enzymology of influenza virus sialidase" in Influenza Virus Sialidase - A Drug Discovery Target, M. Von Itzstein (ed); Springer: New York, 2012, 47-66.
Chan J, Sandhu G, Bennet AJ. A mechanistic study of sialic acid mutarotation: Implications for mutarotase enzymes. Org. Biomol. Chem. 2011, 9, 4818-4822.
Chan J, Lu A, Bennet AJ. Turnover is rate-limited by deglycosylation for Micromonospora viridifaciens sialidase-catalyzed hydrolyses: Conformational implications for the Michaelis complex. J. Am. Chem. Soc. 2011, 133, 2989-2997.
Telford JC, Yeung JHF, Xu G, Kiefel MJ, Watts AG, Hader S, Chan J, Bennet AJ, Moore MM, Taylor GL. The Aspergillus fumigatus sialidase is a 3-deoxy-d-glycero-d-galacto-2-nonulosonic acid hydrolase (KDNase): Structural and mechanistic insights. J. Biol. Chem. 2011, 286, 10783-10792.
Chan J, Lewis AR, Gilbert M, Karwaski M-F, Bennet AJ. A direct NMR method for the measurement of competitive kinetic isotope effects. Nature Chem. Biol. 2010, 6, 405-407.
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