Our Research
1 Cryptic Cysteines, Redox Signaling, & Protein Structure Dynamics
We are interested how redox signaling depends on regulation of protein structure and cysteine solvent accessibility. We've shown this specifies redox signaling networks and think it has implications for understanding protein structure dynamics more broadly.
1 Cryptic Cysteines, Redox Signaling, & Protein Structure Dynamics
We are interested how redox signaling depends on regulation of protein structure and cysteine solvent accessibility. We've shown this specifies redox signaling networks and think it has implications for understanding protein structure dynamics more broadly.
Behring JB, van der Post S, Mooradian AD, Egan MJ, Zimmerman MI, Clements JL, Bowman GR, Held JM. Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation. Sci Signal. 2020 PMID: 31964804; PMCID: PMC7263378
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van der Post S, Birchenough GMH, Held JM. NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation. Cell Reports. 2021. PMID: 33826887.
Highlights
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2 Cancer Biology
We are using genetic and chemical approaches to investigate the specific source(s) of cellular reactive oxygen species (ROS) in cancer cells and tumors. We are also applying cysteine redox proteomics to identify specific molecular targets involved in cancer biology. In many ways this is analogous to the discovery of kinases and phosphorylated substrates many decades ago. We are also interested in metabolism and patient-derived xenografts (PDXs).
We are using genetic and chemical approaches to investigate the specific source(s) of cellular reactive oxygen species (ROS) in cancer cells and tumors. We are also applying cysteine redox proteomics to identify specific molecular targets involved in cancer biology. In many ways this is analogous to the discovery of kinases and phosphorylated substrates many decades ago. We are also interested in metabolism and patient-derived xenografts (PDXs).
Wang X, Mooradian AD, Erdmann-Gilmore P, Zhang Q, Viner R, Davies SR, Huang KL, Bomgarden R, Van Tine BA, Shao J, Ding L, Li S, Ellis MJ, Rogers JC, Townsend RR, Fenyo D, Held JM. Breast tumors educate the proteome of stromal tissue in an individualized but coordinated manner. Science Signaling. 2017. PMCID: PMC5712229.
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3 Computational biology & Bioinformatics
We develop software tools like ProteoClade and ProteoSushi to mine large datasets and integrate multiple 'omics data types.
We develop software tools like ProteoClade and ProteoSushi to mine large datasets and integrate multiple 'omics data types.
4 Chemical Biology
We are interested in developing and applying chemical biology tools like PBZyn to investigate cysteine oxidation and redox processes in a physiologically-relevant context.
We are interested in developing and applying chemical biology tools like PBZyn to investigate cysteine oxidation and redox processes in a physiologically-relevant context.
Clements J, Pohl F, Muthupandi P, Rogers S, Mao J, Doctor A, Birman VB, Held, JM. A clickable probe for versatile characterization of S-nitrosothiols. Redox Biology. 2020 (PDF).
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5 Proteostasis and stress response
Oxidative stress is frequently hypothesized to be a major determinant of aging and disease. However, studies in numerous biological models have demonstrated that redox processes are essential for increased lifespan and healthspan. We are utilizing optogenetic and chemical approaches to decipher the redox signaling pathways involved in stress response pathways in C. elegans.
Oxidative stress is frequently hypothesized to be a major determinant of aging and disease. However, studies in numerous biological models have demonstrated that redox processes are essential for increased lifespan and healthspan. We are utilizing optogenetic and chemical approaches to decipher the redox signaling pathways involved in stress response pathways in C. elegans.