Christopher Chang
Contact:
Christopher J. Chang
Edward and Virginia Taylor Professor of Bioorganic Chemistry
[email protected]
Frick Laboratory, 187
609-258-8819
Faculty Assistant:
Lisa Piscatelli
Faculty / Grants Assistant
[email protected]
Frick Laboratory, 228
609-258-6843
Research Focus
Research Focus
Our laboratory studies the chemistry and biology of the elements. We advance new concepts in imaging, proteomics, drug discovery, and catalysis by drawing from core disciplines of inorganic, organic, and biological chemistry. For example, we have developed activity-based sensing as a general platform to identify transition metals, reactive oxygen species, and one-carbon units as new classes of single-atom signals for allosteric regulation of protein function. These chemical tools also reveal unique metal and redox disease vulnerabilities as targets for innovative drug discovery efforts to treat neurodegeneration, cancer, and metabolic disorders. Representative project areas are summarized below.
Transition Metal Signaling: Bioinorganic Chemistry of the Brain and Body. We are advancing a new paradigm of transition metal signaling, where nutrients like copper and iron serve as dynamic signals to regulate protein function by metalloallostery beyond their traditional roles as active site cofactors. We develop activity-based sensing probes for imaging mobile transition metal pools and activity-based proteomics probes for identifying allosteric metal sites in proteins. These chemical tools enable us to decipher the complex biology of sleep, cognition, and obesity in cell, zebrafish, mouse, and non-human primate models. We also develop medicines to target cuproplasia and cuproptosis, newly recognized forms of copper-dependent cell proliferation and cell death, respectively, as metal-dependent disease vulnerabilities in cancer, neurodegeneration, and metabolic liver disorders.
Activity-Based Sensing: Illuminating One- and Two-Carbon Signaling. We have pioneered the field of activity-based sensing by developing chemical sensors for biological analytes that achieve high selectivity using reaction chemistry rather than conventional lock-and-key binding approaches. Building upon our previous work on selective reactive oxygen and sulfur species detection, we are imaging one- and two-carbon metabolites in organelles, cells, tissues, and animals to elucidate principles of how these signals influence genetic and epigenetic control of cancer metabolism, neurodegeneration, and immune response.
Activity-Based Proteomics: Decoding and Drugging Single-Atom Signaling. We are establishing a field of single-atom signaling, focusing on understanding how reversible addition or removal of a single oxygen atom on proteins can influence their function. We develop activity-based proteomics probes to identify new targets of methionine oxidation as well as writers and erasers that regulate their single-atom biology. Our broader work on protein bioconjugation methods reveal new ligandable hotspots for undruggable protein targets to accelerate the development of next-generation precision medicines that target redox disease vulnerabilities in cancer and neurodegeneration.
Honors
Honors
2024 – ACS Bader Award in Bioorganic or Bioinorganic Chemistry,
2022 – Ivano Bertini Award, International Conference on Copper Biology
2021 – Guggenheim Fellowship
2020 – Humboldt Award
2019 – Sackler Prize in Chemistry
2018 – RSC Jeremy Knowles Award
2017 – Elected Fellow, American Academy of Arts and Sciences
2016 – Cruickshank Award, Gordon Research Conferences
2015 – Fellow, Royal Society of Chemistry
2015 – Blavatnik National Award in Chemistry
2014 – Sackler Professor, UC Berkeley/UCSF
2013 – Baekeland Award, ACS New Jersey Section
2013 – Noyce Prize for Excellence in Undergraduate Teaching, UC Berkeley
2013 – ACS Nobel Laureate Signature Award in Graduate Education
2012 – RSC Chemistry of Transition Metals Award
2012 – ACS Eli Lilly Award in Biological Chemistry
2011 – Wilson Prize, Harvard University
2011 – Miller Institute Professor, UC Berkeley
2011 – Society for Biological Inorganic Chemistry Early Career Award
2010 – ACS Cope Scholar Award
2009 – Novartis Early Career Award
2009 – Astra Zeneca Excellence in Chemistry Award
2008 – Howard Hughes Medical Institute Investigator
2008 – Technology Review TR35 Young Innovator
2008 – Bau Award in Inorganic Chemistry
2008 – Hellman Faculty Award
2008 – Amgen Young Investigator Award
2008 – Paul Saltman Award, Metals in Biology Gordon Research Conference
2007 – Sloan Fellowship
2006 – Packard Fellowship
2006 – NSF CAREER Award
2005 – Beckman Young Investigator
2005 – American Federation for Aging Research Award
2004 – Dreyfus New Faculty Award
Selected Publications
“Oxidative cyclization reagents reveal tryptophan cation-pi interactions”, Xie, X.; Moon, P. J.; Crossley, S. W. M.; Bischoff, A. J.; He, D.; Li, G.; Dao, N.; Gonzalez-Valero, A.; Reeves, A. G.; McKenna, J. M.; Elledge, S. K.; Wells, J. A.; Toste, F. D.*; Chang, C. J.* Nature 2024, 627, 680-687.
“Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism”, Pham, V. N.; Bruemmer, K. J.; Toh, J. D.; Ge, E. J.; Tenney, L.; Ward, C. C.; Dingler, F. A.; Millington, C. L.; Garcia-Prieto, C. A.; Pulos-Homes, M. C.; Ingolia, N. T.; Bontel, L. B.; Esteller, M.; Patel, K. J.; Nomura, D. K.; Chang, C. J.* Science 2023, 382, 1-10.
“Oxidation state-specific fluorescent copper sensors reveal oncogene-driven redox changes that regulate labile copper(II) pools”, Pezacki, A. T.; Matier, C. D.; Gu, X,; Kummelstedt, E.; Bond, S. E.; Torrente, L; Jordan-Sciutto, K. L.; DeNicola, G. M.; Su, T. A.; Brady, D. C.; Chang, C. J.* Proc. Natl. Acad. Sci. USA 2022, 119, e2202736119.
“A tandem activity-based sensing and labeling strategy enables imaging of transcellular hydrogen peroxide signaling”, Iwashita, H.; Castillo, E.; Messina, M. S.; Swanson, R.A.; Chang, C. J.* Proc. Natl. Acad. Sci. USA 2021, 118, e2018513118.
“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.
“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.
“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.
“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.
“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.
“A Molecular MoS2 Edge Site Mimic for Catalytic Hydrogen Generation”, Karunadasa, H. I.; Montalvo, E.; Sun, Y.; Majda, M.; Long, J. R.; Chang, C. J.* Science 2012, 335, 698-702.
“Calcium-dependent copper redistributions in neuronal cells revealed by a fluorescent copper sensor and X-ray fluorescence microscopy”, Dodani, S. C.; Domaille, D. W.; Nam, C. I.; Miller, E. W.; Finney, L. A.; Vogt, S.; Chang, C. J.* Proc. Natl. Acad. Sci. USA 2011, 108, 5980-5985.
“Aquaporin-3 Mediates Hydrogen Peroxide Uptake to Regulate Downstream Intracellular Signaling”, Miller, E. W.; Dickinson, B. C.; Chang, C. J.* “Proc. Natl. Acad. Sci. USA 2010, 107, 15681-15686.
“Molecular Imaging of Hydrogen Peroxide Produced for Cell Signaling”, Miller, E. W.; Tulyathan, O.; Isacoff, E. Y.; Chang, C. J.* Nature Chem. Biol. 2007, 3, 263-267.
“A Selective, Cell-Permeable Optical Probe for Hydrogen Peroxide in Living Cells”, Chang, M. C. Y.; Pralle, A.; Isacoff, E. Y.; Chang, C. J.* J. Am. Chem. Soc. 2004, 126, 15392-15393.
Selected Reviews
“Metalloallostery and Transition Metal Signalling: Bioinorganic Copper Chemistry Beyond Active Sites”, Pham, V. N.; Chang, C. J.* Angew. Chem. Int. Ed. 2023, 62, e202213644.
“Connecting copper and cancer: from transition metal signalling to metalloplasia”, Ge, E. J.; Bush, A. I.; Casini, A.; Cobine, P. A.; Cross, J. R.; DeNicola, G. M.; Dou, Q. P.; Franz, K. J.; Gohil, V. M.; Gupta, S.; Kaler, S. G.; Lutsenko, S.; Mittal, V.; Petris, M. J.; Polishchuk, R.; Ralle, M.; Schilsky, M. L.; Tonks, N. K.; Vahdat, L. T.; Aelst, L. V.; Xi, D.; Yuan, P.; Brady, D. C.; Chang, C. J.* Nature Rev. Cancer. 2022, 22, 102–113.
“Activity-Based Sensing: A Synthetic Methods Approach for Selective Molecular Imaging and Beyond”, Bruemmer, K. J.; Crossley, S. W. M.; Chang, C. J.* Angew. Chem. Int. Ed. 2020, 59, 13734–13762.
“Hybrid Catalysts for Artificial Photosynthesis: Merging Approaches from Molecular, Materials, and Biological Catalysis”, Smith, P. T,; Nichols, E. M.; Cao, Z.; Chang, C. J.* Acc. Chem. Res. 2020, 53, 575–587.
“Searching for Harmony in Transition-Metal Signaling”, Chang, C. J.* Nature Chem. Biol. 2015, 111, 744-747.
“Reaction-based small-molecule fluorescent probes for chemoselective bioimaging”, Chan, J.; Dodani, S. C.; Chang, C. J.* Nat. Chem. 2012, 4, 973-984.
“Boronate Oxidation as a Bioorthogonal Reaction Approach for Studying the Chemistry of Hydrogen Peroxide in Living Systems”, Lippert, A. R.; Van de Bittner, G. C.; Chang, C. J.* Acc. Chem. Res. 2011, 44, 793-804.
“Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging”, Que, E. L.; Domaille, D. W.; Chang, C. J.* Chem. Rev. 2008, 108, 1517-1549.
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