Faculty Research Page
Class of 1942 Chair and Professor of Biochemistry, Biophysics and Structural Biology*
*And of Chemistry
Chemical Biology: Chemical Approaches to Decipher Metal and Redox Biology
Our laboratory works at the chemistry/biology interface, where we study metals in biology and energy by pursuing new concepts in sensing and catalysis. We have developed activity-based sensing (ABS) as a general technology platform to enable biological applications and innovate imaging and diagnostics, proteomics, and drug discovery. These new chemical tools have identified copper, hydrogen peroxide, and formaldehyde as signals for regulating processes spanning neural activity and neurodegeneration to cancer and fat metabolism, opening a field of transition metal signaling. We are advancing artificial photosynthesis through the development of molecular catalysts for sustainable electrosynthesis that mimic enzyme biocatalysts or heterogeneous materials catalysts, as well as hybrid catalysts that merge design concepts from molecular, materials, and biological catalysts. Representative project areas are summarized below.
The Chang Lab, 2020
Transition Metal Signaling: Metalloallostery in the Brain and Beyond. We are advancing a new paradigm of transition metal signaling, where essential nutrients like copper and iron can serve as dynamic signals for biology by binding to metalloallosteric sites to regulate protein function beyond traditional active sites. We are developing activity-based sensing (ABS) probes for fluorescence and bioluminescence imaging of dynamic transition metal pools, chemoproteomic identification and biochemical characterization of new metalloprotein targets, and drug discovery to treat disease within the lens of metalloplasias. We work across cell, zebrafish, and mouse models to study transition metal signaling in cancer, obesity and fatty liver disease, and neurodegenerative diseases.
Activity-Based Sensing: Redox and One-Carbon Signaling. We are developing the concept of activity-based sensing (ABS), which is an emerging field that utilizes chemical reactivity rather than conventional lock-and-key binding to probe and manipulate biological systems. We are creating activity-based probes for fluorescence and bioluminescence imaging of reactive oxygen species and one-carbon units, as well as bioconjugation chemistry, chemoproteomics, and drug discovery to identify and drug new targets of redox and one-carbon signaling and metabolism in cell and animal models.
Artificial Photosynthesis: Catalyzing Sustainable Electrosynthesis. We are developing catalysts for sustainable electrosynthesis to address changing climate and rising global energy demands. Inspired by natural photosynthesis, which catalyzes conversion of the abundant chemical resources of light, water, and carbon dioxide to produce the value-added products needed to sustain life, we are taking a unified approach to this small-molecule activation problem by creating molecular electrocatalysts for carbon dioxide reduction and nitrogen/phosphorus cycling that draw on design principles from molecular, materials, and biological catalysis and operate in water.
1. "Searching for Harmony in Transition-Metal Signaling", Chang, C. J. Nature Chem. Biol. 2015, 111, 744-747.
2. "Copper regulates cyclic-AMP-dependent lipolysis", Krishnamoorthy, L.; Cotruvo Jr., J. A.; Chan, J.; Kaluarachchi, H.; Muchenditsi, A.; Pendyala, V. S.; Jia, S.; Aron, A. T.; Ackerman, C. M.; Wander Wal, M. N.; Guan, T.; Smaga, L. P.; Farhi, S. L.; New, E. J.; Lutsenko, S.; Chang, C. J. Nature Chem. Biol. 2016, 12, 586-593.
3. "In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease", Heffern, M. C.; Park, H. M.; Au-Yeung, H. Y.; Van de Bittner, G. C.; Ackerman, C. M.; Stahl, A. Chang, C. J. Proc. Natl. Acad. Sci. USA 2016, 113, 14219-14224.
4. "Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system", Xiao, T.; Ackerman, C. M.; Carroll, E. C.; Jia, S.; Hoagland, A.; Chan, J.; Thai. B.; Liu, C. S.; Isacoff, E. Y.; Chang, C. J. Nature Chem. Biol. 2018, 14, 655-663.
5. "Activity-based ratiometric FRET probe reveals oncogene-driven changes in labile copper pools induced by altered glutathione metabolism", Chung, C. Y.; Posimo, J. M.; Lee, S.;, Tsang, T.; Davis, J. M.; Brady, D. C.; Chang, C. J. Proc. Natl. Acad. Sci. USA 2019, 116, 18285-18294.
6. "Redox-based reagents for chemoselective methionine bioconjugation", Lin, S.; Yang, X.; Jia, S.; Weeks, A. M.; Hornsby, M.; Lee, P. S.; Nichiporuk, R. V.; Iavarone, A. T.; Wells, J. A.; Toste, F. D.; Chang, C. J. Science 2017, 355, 597-602.
Last Updated 2020-03-11