BIOINORGANIC CHEMISTRY

TRANSITION METAL SIGNALING

The traditional view of metals in biology is that redox-inactive alkali and alkaline metals like sodium, potassium, and calcium are broadly used for cell signaling, whereas redox-active transition metals like copper and iron are solely metabolic cofactors that must be buried and tightly-bound within protein active sites to protect the cell from potential oxidative stress and damage. Our work breaks this narrow mold by establishing a new paradigm of transition metal signaling, where these essential nutrients can also serve as dynamic cellular messengers. We are developing fluorescent, bioluminescent, and PET probes to image transition metal pools, chemoproteomics probes to identify and characterize new metalloprotein targets, and optogenetic constructs to manipulate transition metal signals in cell, tissue, and zebrafish and mouse models. These chemical tools are being applied to study the contributions of transition metal signaling to fat metabolism in obesity, diabetes, and cancer along with neural circuitry.


REVIEWS

Chang, C. J. "Bioinorganic Life and Neural Activity: Toward a Chemistry of Consciousness?", Acc. Chem. Res. 2017, 50, 535-538. [html] [pdf]




Ackerman, C. M.; Lee, S.; Chang, C. J. "Analytical Methods for Imaging Metals in Biology: From Transition Metal Metabolism to Transition Metal Signaling", Anal. Chem. 2017, 89, 22-41. [html] [pdf]




Chang, C. J. "Searching for Harmony in Transition-Metal Signaling", Nat. Chem. Biol. 2015, 111, 744-747. [html] [pdf]




Aron, A. T.; Ramos-Torres, K. M.; Cotruvo, Jr., J. A.; Chang, C. J. "Recognition- and Reactivity-Based Fluorescent Probes for Studying Transition Metal Signaling in Living Systems", Acc. Chem. Res. 2015, 48, 2434-2442. [pdf]





REPRESENTATIVE PAPERS

Heffern, M. C.; Park, H. M.; Au-Yeung, H. Y.; Van de Bittner, G. C.; Ackerman, C. M.; Stahl, A. Chang, C. J. "In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease", Proc. Natl. Acad. Sci. USA 2016, 113, 14219-14224. [html] [pdf]




Lee, S.; Barin, G.; Ackerman, C. M.; Muchenditsi, A.; Xu, J.; Reimer, J. A.; Lutsenko, S.; Long, J. R.; Chang, C. J. "Copper Capture in a Thioether-Functionalized Porous Polymer Applied to the Detection of Wilson's Disease", J. Am. Chem. Soc. 2016, 138, 7603-7609. [html] [pdf]




Krishnamoorthy, L.; Cotruvo, Jr., J. A.; Chan, J.; Kaluarachchi, H.; Muchenditsi, A.; Pendyala, V. S.; Jia, S.; Aron, A. T.; Ackerman, C. M.; Vander Wal, M. N.; Guan, T.; Smaga, L. P.; Farhi, S. L.; New, E. J.; Lutsenko, S.; Chang, C. J. "Copper regulates cyclic-AMP-dependent lipolysis", Nat. Chem. Biol. 2016, 12, 586-592. [html] [pdf] [UC Science Today Segment] [PictureFit YouTube video] [LBNL News Story] [UC Berkeley News Story] [Daily Mail News Story] [Genetic Engineering and Biotechnology News Story] [Dr Oz Reviews Story] [Men's Fitness Story] [Deccan Herald News Story] [Fitness First Mag Story] [Indo Asian News Service Story] [Health Canal News Story] [First Post News Story] [Business Standard News Story] [The Health Site News Story] [Hindustan Times News Story] [Can-India News Story] [Natural Science News Story] [Times of India News Story] [Money Control News Story] [American Council on Science and Health News Story] [China Topix News Story] [MSN News Story] [Press Liberal News Story] [Headlines News Story] [The Sentinel News Story] [Brief Report News Story] [Engine News Story] [3 Novices News Story] [HT Syndication News Story] [New York Indian News Story]




Dodani, S. C.; Firl, A.; Chan, J.; Nam, C. I.; Aron, A. T.; Onak, C. S.; Ramos-Torres, K. M.; Paek, J.; Webster, C. W.; Feller, M. B.; Chang, C. J. "Copper is an endogenous modulator of neural circuit spontaneous activity", Proc. Natl. Acad. Sci. USA 2014, 111, 16280-16285. [html] [pdf]




Hong-Hermesdorf, A.; Miethke, M.; Gallaher, S. D.; Kropat, J.; Dodani, S. C.; Chan, J.; Barupala, D.; Domaille, D. W.; Shirasaki, S. I.; Loo, J. A.; Weber, P. K.; Pett-Ridge, J.; Stemmler, T. L.; Chang, C. J.; Merchant, S. S. "Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas", Nat. Chem. Biol. 2014, 10, 1034-1042. [html] [pdf]




Au-Yeung, H. Y.; Chan, J.; Chantarojsiri, T.; Chang, C. J. "Molecular Imaging of Labile Iron(II) Pools in Living Cells with a Turn-On Fluorescent Probe", J. Am. Chem. Soc. 2013, 135, 15165-15173. [html] [pdf]




Hirayama, T.; Van de Bittner, G. C.; Gray, L. W.; Lutsenko, S.; Chang, C. J. "Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model", Proc. Natl. Acad. Sci. USA 2012, 109, 2228-2233. [pdf] [html]







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Updated 2 Jun 2017