Reactive oxygen species (ROS) are a class of small molecules that play important roles in human health, aging, and disease. Imbalances in the production and consumption of ROS cause oxidative stress and damage of proteins, lipids, and nucleic acids, which can in turn lead to functional decline of tissues and organs over time and contribute to major diseases ranging from cancer to cardiovascular disorders to neurodegenerative diseases. At the same time, emerging data shows that one particular ROS, hydrogen peroxide (H2O2), can also be produced for physiological signaling purposes to mediate processes, from wound healing to neurotransmission, by regulating cell growth, differentiation, and migration pathways in a manner akin to the canonical small-molecule signal nitric oxide (NO). We are developing and applying new chemical tools for molecular imaging of H2O2 with the long-term goal of understanding how and in what context this oxygen metabolite contributes to normal physiology, aging, and disease.
Specific aims for this competitive renewal submission include developing new probes that will allow chemoselective imaging of H2O2 with subcellular resolution, creating new imaging agents that can be used to monitor H2O2 fluxes in living organisms by near-IR fluorescence or bioluminescence modalities, and applying these and related chemical tools for elucidating the contributions of H2O2 production to signaling and stress pathways in neural stem cells and neurons.

Public Health Relevance

Hydrogen peroxide and related reactive oxygen species can cause oxidative stress and damage of tissues and organs during aging and in age-related diseases ranging from cancer to heart disease to neurodegenerative disorders, but these molecules can also be produced on demand for beneficial processes like wound healing, neurotransmission, and sensing pain. We are developing and applying new chemical tools for molecular imaging of hydrogen peroxide with the long-term goal of understanding how and in what context this small molecule messenger contributes to normal physiology, aging, and disease.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
Schools of Arts and Sciences
United States
Zip Code
Burgos-Barragan, Guillermo; Wit, Niek; Meiser, Johannes et al. (2017) Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature 548:549-554
Ladomersky, Erik; Khan, Aslam; Shanbhag, Vinit et al. (2017) Host and Pathogen Copper-Transporting P-Type ATPases Function Antagonistically during Salmonella Infection. Infect Immun 85:
Lin, Shixian; Yang, Xiaoyu; Jia, Shang et al. (2017) Redox-based reagents for chemoselective methionine bioconjugation. Science 355:597-602
Brewer, Thomas F; Burgos-Barragan, Guillermo; Wit, Niek et al. (2017) A 2-aza-Cope reactivity-based platform for ratiometric fluorescence imaging of formaldehyde in living cells. Chem Sci 8:4073-4081
Camarena, Vladimir; Sant, David W; Huff, Tyler C et al. (2017) cAMP signaling regulates DNA hydroxymethylation by augmenting the intracellular labile ferrous iron pool. Elife 6:
Heffern, Marie C; Park, Hyo Min; Au-Yeung, Ho Yu et al. (2016) In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A 113:14219-14224
Krishnamoorthy, Lakshmi; Cotruvo Jr, Joseph A; Chan, Jefferson et al. (2016) Copper regulates cyclic-AMP-dependent lipolysis. Nat Chem Biol 12:586-92
Rodella, Umberto; Scorzeto, Michele; Duregotti, Elisa et al. (2016) An animal model of Miller Fisher syndrome: Mitochondrial hydrogen peroxide is produced by the autoimmune attack of nerve terminals and activates Schwann cells. Neurobiol Dis 96:95-104
Tomalin, Lewis Elwood; Day, Alison Michelle; Underwood, Zoe Elizabeth et al. (2016) Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed. Free Radic Biol Med 95:333-48
Akassoglou, Katerina; Agalliu, Dritan; Chang, Christopher J et al. (2016) Neurovascular and Immuno-Imaging: From Mechanisms to Therapies. Proceedings of the Inaugural Symposium. Front Neurosci 10:46

Showing the most recent 10 out of 82 publications