Chemical Biology and Inorganic Chemistry: New chemical tools for imaging and proteomics in the brain and central nervous system; new molecular, biological, and materials catalysts for energy conversion and solar fuels
Research in our group spans the core disciplines of chemical biology, inorganic chemistry, organic chemistry, and molecular biology, focusing on the fundamental design and synthesis of new molecules and materials for targeted applications of interest. We create new chemical tools for molecular imaging and activity-based protein profiling to discover and study novel chemical signals in biology, with a particular focus on neuroscience. Our work in inorganic chemistry centers on development of catalysts for energy conversion and solar fuels, 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.
Chemical Biology: New Chemical Tools for Mapping Brain Activity. The distinctive role of the brain in forming the center of consciousness offers a grand challenge for achieving a molecular-level understanding of its unique functions, including learning and memory, as well as senses like sight, smell, and taste. As such, the brain also represents a frontier for developing new therapeutics for aging, stroke, and neurodegenerative diseases. We are creating new chemical tools to image and optically manipulate the underlying molecular signals that govern information transfer in neural circuits in live-cell culture and zebrafish and mouse models, ranging from ion channels to cellular messengers based on reactive oxygen and sulfur species.
Bioinorganic Chemistry: Metals in Neurobiology and Infectious Diseases. The specialized physiology of the brain relies on the existence of unique chemistry that is not found elsewhere in the body. For reasons that are not currently understood, the brain accumulates unexpected chemical elements at higher concentrations than any other organ or tissue, including redox-active metals like copper and iron, but these same elements are misregulated in neurological disorders such as Alzheimer's disease and autism. We are developing new fluorescent sensors for tracking dynamic metal ion pools in living cells and animals, as well as activity-based protein probes for identifying metal targets in stages of neural signaling and neurodegeneration. These tools are also being applied to cell, zebrafish, and mouse models of inflammation and infectious diseases like tuberculosis.
Organic Chemistry and Chemical Biology: Reaction-Based Imaging and Proteomics Probes for Studying Cell Signaling. 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 developing small-molecule fluorescent, MRI, and PET imaging probes that exploit selective, bioorthogonal chemistries to report on specific analytes in live cells and animals, with particular interest in reactive oxygen and sulfur species, carbon monoxide, and reversible post-translational modifications involving dynamic redox regulation.
Inorganic Chemistry: Energy Catalysis and Solar Fuels. 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 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 fuel chemistry.
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 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); Baekeland Award, ACS New Jersey Section (2013).