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)
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Synthetic and Biological Chemistry A Study Section (SBCA)
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Fabian, Miles
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University of California Berkeley
Schools of Arts and Sciences
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Lin, Vivian S; Chen, Wei; Xian, Ming et al. (2015) Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems. Chem Soc Rev 44:4596-618
Huang, Carlos P; Fofana, Mariama; Chan, Jefferson et al. (2014) Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin. Metallomics 6:654-61
Yang, Ming; Haase, Astrid D; Huang, Fang-Ke et al. (2014) Dephosphorylation of tyrosine 393 in argonaute 2 by protein tyrosine phosphatase 1B regulates gene silencing in oncogenic RAS-induced senescence. Mol Cell 55:782-90
Basu, Subhasree; Rajakaruna, Suren; Dickinson, Bryan C et al. (2014) Endogenous hydrogen peroxide production in the epithelium of the developing embryonic lens. Mol Vis 20:458-67
Banerjee, Jaideep; Das Ghatak, Piya; Roy, Sashwati et al. (2014) Improvement of human keratinocyte migration by a redox active bioelectric dressing. PLoS One 9:e89239
Polishchuk, Elena V; Concilli, Mafalda; Iacobacci, Simona et al. (2014) Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. Dev Cell 29:686-700
Kashyap, Des Raj; Rompca, Annemarie; Gaballa, Ahmed et al. (2014) Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress. PLoS Pathog 10:e1004280
Carroll, Valerie; Michel, Brian W; Blecha, Joseph et al. (2014) A boronate-caged [ยน?F]FLT probe for hydrogen peroxide detection using positron emission tomography. J Am Chem Soc 136:14742-5
Hong-Hermesdorf, Anne; Miethke, Marcus; Gallaher, Sean D et al. (2014) Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas. Nat Chem Biol 10:1034-42
Van de Bittner, Genevieve C; Bertozzi, Carolyn R; Chang, Christopher J (2013) Strategy for dual-analyte luciferin imaging: in vivo bioluminescence detection of hydrogen peroxide and caspase activity in a murine model of acute inflammation. J Am Chem Soc 135:1783-95

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