Class of 1942 Chair
Professor of Chemistry
Professor of Molecular and Cell Biology
Investigator, Howard Hughes Medical Institute
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
Inorganic Chemistry and Chemical Biology: New chemical tools for imaging, proteomics, and optogenetics in neurobiology, metabolism, and cancer; new molecular, materials, and biological catalysts for solar-to-chemical conversion
Our laboratory focuses on fundamental design and synthesis of new molecules and materials to address specific problems of broader societal interest. Drawing from core disciplines of inorganic and organic chemistry and molecular biology, as well as emerging fields spanning chemical biology to materials and nanoscience, we develop new chemical tools for molecular imaging, chemoproteomics, and optogenetics to identify and study novel chemical signals in biology, with a particular focus on neuroscience, metabolism, and cancer. Our inorganic program centers on solar-to-chemical conversion, where we merge concepts and components of molecular inorganic chemistry with biology and materials science to synthesize catalysts that operate in environmentally-green, aqueous conditions.
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.
Biochemistry and Molecular Biology: Metals in Neurobiology. The unique biology of the brain as the center of consciousness, from learning and memory to senses like sight, smell, and taste, is underpinned by unique chemistry that remains insufficiently understood. In particular, we are interested in understanding why the brain accumulates unexpected chemical elements at higher concentrations than any other organ or tissue, including redox-active metals like copper and iron, where at the same time these elements are misregulated in neurological disorders such as Alzheimer's and Parkinson's diseases and autism. Using CRISPR, optogenetics, high-resolution mass spec imaging, and behavioral assays, we are developing and studying new zebrafish and mouse models to explore the roles of transition metals in neural signaling and neurodegeneration.
Chemical Biology: Redox Imaging, Proteomics, and Optogenetics. Traditional methods for sensing rely on static lock-and-key binding approaches, which are difficult to apply to reactive, transient small molecules in complex biological settings. We are synthesizing small-molecule fluorescent, MRI, and PET imaging probes that exploit chemoselective, bioorthogonal chemistries to report on specific analytes in living cells and animals, with particular interest in the redox biology of reactive oxygen, sulfur, and carbonyl species. We are also developing new bioconjugation reactions for chemoproteomics as well as small-molecule inhibitor and antibody-drug conjugate therapeutics. Finally, we are creating optogenetic tools for controlling redox signals that govern information transfer in neural circuits in live-cell culture and mouse models.
Inorganic and Materials Chemistry: Energy Catalysis and Solar-to-Chemical Conversion. New catalysts for carbon-neutral energy conversion processes are essential to addressing climate change and rising global energy demands. We are taking a unified approach to this small-molecule activation problem by developing molecular inorganic, biological, and materials catalysts for carbon dioxide reduction and water splitting that can be used in parallel under environmentally green, aqueous conditions. Biology and materials science provide concepts as well as components to develop new solar-to-chemical conversion processes. Molecular materials derived from metal-organic and covalent organic frameworks and related porous cages, along with molecular-nanoparticle composites, complement molecular inorganic catalyst designs.
Materials Biology. Our work at the materials biology interface is inspired by natural photosynthesis, which harnesses solar energy to convert carbon dioxide and water to the value-added products needed to sustain life; however, the chemical end products are limited to biomass, a complex mixture required to make the plant's food and body. We are developing a hybrid inorganic-biological approach that can go beyond natural photosynthesis by creating cyborg cells that are capable of synthesizing a specific complex chemical product from carbon dioxide and water with sustainable solar and/or electrical input, spanning fuels, foods, medicines, and materials. In the longer term, this materials biology platform has the potential to endow photosynthetic capabilities to any living cell or organism.
Professor; 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).