Christopher J. Chang

Chris Chang

Class of 1942 Chair
Professor of Chemistry
Professor of Molecular and Cell Biology
Member, Helen Wills Neuroscience Institute
Adjunct Professor, UCSF

chrischang@berkeley.edu
office: 532A Latimer
lab: 401, 437 Latimer and 572, 574, and 584 Tan
phone: (510) 642-4704
fax: (510) 642-7301
lab phone: (510) 643-4160, (510) 643-9522

Research Group URL
Recent Publications


Research Interests

Chemical Biology and Inorganic Chemistry; Bioinorganic Chemistry

Our laboratory studies the chemistry of biology and energy, where we advance new concepts in imaging, proteomics, drug discovery, and catalysis. Our work draws from core disciplines of inorganic, organic, and biological chemistry and features a diverse range of elements across the periodic table of life. We have developed activity-based sensing (ABS) as a general platform for biology and medicine, enabling broad applications of this technology to imaging, proteomics, and drug discovery. These chemical tools have identified copper, hydrogen peroxide, and formaldehyde as signals for allosteric regulation of protein function to open new fields of transition metal signaling, metalloallostery, and single-atom signaling, impacting areas of health and disease spanning neural activity and neurodegeneration to cancer, obesity, and metabolic diseases. Our work in artificial photosynthesis uses design concepts from biology to develop new molecular and hybrid catalysts for sustainable electrosynthesis applied to global challenges in carbon dioxide capture and conversion and nitrogen/phosphorus cycles. Representative project areas are summarized below.

Transition Metal Signaling: From Metalloallostery to Metalloplasia 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 signaling messengers to regulate protein function beyond their traditional roles as static active site cofactors. We develop activity-based sensing fluorescent probes for imaging mobile transition metal pools and activity-based proteomics probes for discovery and characterization of enzymes regulated by metalloallostery. These chemical tools enable us to decipher complex biology such as sleep behavior and fat metabolism at a molecular and systems level. Working across cell, zebrafish, and mouse models, we identify disease vulnerabilities to metal nutrients to develop new modalities for drug discovery, such as targeting metalloplasias that rely on metal-dependent cell proliferation in cancer, neurodegenerative diseases, and metabolic liver diseases.

Activity-Based Sensing: Imaging Redox and One-Carbon Signaling. We are advancing the field of activity-based sensing, which exploits molecular reactivity, rather than molecular recognition with conventional lock-and-key binding, to design chemical sensors for biological discovery that achieve high specificity and spatiotemporal resolution. We create activity-based sensing probes to visualize fluxes of transient reactive oxygen species and one-carbon metabolites using fluorescence and other imaging modalities. We apply these chemical tools in profiling assays at the single-cell, tissue, and animal level to identify and elucidate principles of redox and one-carbon biology, including sources and scavengers of reactive molecular signals.

Activity-Based Proteomics: From Single-Atom Signaling to Redox Drug Discovery. We are advancing the concept of single-atom signaling, deciphering how site-specific allosteric modification of a protein with just a single element can regulate its function. We focus on the reversible redox cycling between methionine and methionine sulfoxide and the writers and erasers that install and remove these one-oxygen post-translational modifications. We develop synthetic methods for bioconjugation to native amino acids for use from proteins to proteomes, enabling platforms such as activity-based protein profiling to find novel sites for allosteric protein regulation. In turn, we translate our findings to target these newly-discovered druggable hotspots in cancer and other diseases using small-molecule covalent ligand libraries, antibody-drug conjugates, and related therapeutic modalities.

Artificial Photosynthesis: Catalyzing Sustainable Electrosynthesis. We develop 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 capture and conversion as well as nitrogen/phosphorus cycling that draw on design principles from molecular, materials, and biological catalysis and operate in water.

Biography

  • Born 1974
  • B.S./M.S. California Institute of Technology (1997)
  • Fulbright Fellow Université Louis Pasteur (1997-1998)
  • Ph.D. Massachusetts Institute of Technology (2002)
  • NSF Predoctoral Fellow (1998-2001)
  • MIT/Merck Foundation Predoctoral Fellow (2001-2002)
  • Jane Coffin Childs Postdoctoral Fellow, MIT (2002-2004)
  • Davison Thesis Prize (MIT, 2003)
  • Dreyfus New Faculty Award (2004)
  • Beckman Young Investigator Award (2005)
  • American Federation for Aging Research Award (2005)
  • NSF CAREER Award (2006)
  • Packard Fellowship (2006)
  • Sloan Fellowship (2007)
  • Saltman Award, Metals in Biology GRC (2008)
  • Amgen Young Investigator Award (2008)
  • Hellman Faculty Award (2008)
  • Bau Family Award in Inorganic Chemistry (2008)
  • Technology Review TR35 Young Innovator Award (2008)
  • Howard Hughes Medical Institute Investigator (2008)
  • Astra Zeneca Excellence in Chemistry Award (2009)
  • Novartis Early Career Award (2009)
  • ACS Cope Scholar Award (2010)
  • SBIC Early Career Award (2011)
  • Wilson Prize, Harvard University (2011)
  • Miller Research Professor (2011-2012)
  • ACS Eli Lilly Award in Biological Chemistry (2012)
  • RSC Award in Transition Metal Chemistry (2012)
  • ACS Nobel Laureate Signature Award in Graduate Education (2013)
  • Noyce Prize for Excellence in Undergraduate Teaching (2013)
  • ACS Baekeland Award (2013)
  • Sackler Professor, UC Berkeley/UCSF (2014-2015)
  • Fellow, Royal Society of Chemistry (2015)
  • Blavatnik Award in Chemistry (2015)
  • Cruickshank Award, Gordon Research Conferences (2016)
  • Member, American Academy of Arts and Sciences (2017)
  • RSC Jeremy Knowles Award (2018)
  • Sackler Prize in Chemistry (2019)
  • Humboldt Research Award (2020)
  • Guggenheim Fellowship (2021)