publications

2022

1. Molecular dynamics and functional characterization of I37R-CFTR lasso mutation provide insights into channel gating activity

   Wong, Sharon L., Awatade, Nikhil T., Astore, Miro A., Allan, Katelin M., Carnell, Michael J., Slapetova, Iveta, Chen, Po-chia, Capraro, Alexander, Fawcett, Laura K., Whan, Renee M., Griffith, Renate, Ooi, Chee Y., Kuyucak, Serdar, Jaffe, Adam, and Waters, Shafagh A.

   iScience Jan 2022
2. Tracking Policy Implications and Impacts of the COVID-19 Pandemic and Related Executive Actions on a Sampling of Foreign-born Early Career Researchers in the U.S.

   Jorgensen, Christian, Vedachalam, Sridhar, Astore, Miro Alexander, Mughal, Amreen, Lay, Maiko Le, Bankston, Adriana, and Singh, Harinder

   Jan 2022

2021

1. Molecular dynamics and theratyping in airway and gut organoids reveal R352Q-CFTR conductance defect

   Wong, Sharon L., Awatade, Nikhil T., Astore, Miro A., Allan, Katelin M., Carnell, Michael J., Slapetova, Iveta, Chen, Po-chia, Setiadi, Jeffry, Pandzic, Elvis, Fawcett, Laura K., Widger, John R., Whan, Renee M., Griffith, Renate, Ooi, Chee Y., Kuyucak, Serdar, Jaffe, Adam, and Waters, Shafagh A.

   bioRxiv Aug 2021

   Abs

   A significant challenge to making targeted CFTR modulator therapies accessible to all individuals with cystic fibrosis (CF) are many mutations in the CFTR gene that can cause CF, most of which remain uncharacterized. Here, we characterized the structural and functional defects of the rare CFTR mutation R352Q – with potential role contributing to intrapore chloride ion permeation – in patient-derived cell models of the airway and gut. CFTR function in differentiated nasal epithelial cultures and matched intestinal organoids was assessed using ion transport assay and forskolin-induced swelling (FIS) assay respectively. Two CFTR potentiators (VX-770, GLPG1837) and a corrector (VX-809) were tested. Data from R352Q-CFTR were compared to that of participants with mutations with known impact on CFTR function. R352Q-CFTR has residual CFTR function which was restored to functional CFTR activity by CFTR potentiators but not the corrector. Molecular dynamics (MD) simulations of R352Q-CFTR were carried out which indicated the presence of a chloride conductance defect, with little evidence supporting a gating defect. The combination approach of in vitro patient-derived cell models and in silico MD simulations to characterize rare CFTR mutations can improve the specificity and sensitivity of modulator response predictions and aid in their translational use for CF precision medicine. ### Competing Interest Statement SAW is the recipient of a Vertex Innovation Grant (2018) and a TSANZ/Vertex Research Award (2020). Both are unrelated and outside of the submitted manuscript. AJ has received consulting fees from Vertex on projects unrelated to this study. CYO has acted as consultant and on advisory boards for Vertex pharmaceuticals. These works are unrelated to this project and manuscript. All other authors declare no conflict of interest.

2019

1. Global redox proteome and phosphoproteome analysis reveals redox switch in Akt

   Su, Zhiduan, Burchfield, James G., Yang, Pengyi, Humphrey, Sean J., Yang, Guang, Francis, Deanne, Yasmin, Sabina, Shin, Sung Young, Norris, Dougall M., Kearney, Alison L., Astore, Miro A., Scavuzzo, Jonathan, Fisher-Wellman, Kelsey H., Wang, Qiao Ping, Parker, Benjamin L., Neely, G. Gregory, Vafaee, Fatemeh, Chiu, Joyce, Yeo, Reichelle, Hogg, Philip J., Fazakerley, Daniel J., Nguyen, Lan K., Kuyucak, Serdar, and James, David E.

   Nature Communications Dec 2019

   Abs Bib

   Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases.

   @article{Su2019a,
     bibtex_show = {true},
     author = {Su, Zhiduan and Burchfield, James G. and Yang, Pengyi and Humphrey, Sean J. and Yang, Guang and Francis, Deanne and Yasmin, Sabina and Shin, Sung Young and Norris, Dougall M. and Kearney, Alison L. and Astore, Miro A. and Scavuzzo, Jonathan and Fisher-Wellman, Kelsey H. and Wang, Qiao Ping and Parker, Benjamin L. and Neely, G. Gregory and Vafaee, Fatemeh and Chiu, Joyce and Yeo, Reichelle and Hogg, Philip J. and Fazakerley, Daniel J. and Nguyen, Lan K. and Kuyucak, Serdar and James, David E.},
     doi = {10.1038/s41467-019-13114-4},
     file = {:home/miro/.local/share/data/Mendeley Ltd./Mendeley Desktop/Downloaded/Su et al. - 2019 - Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.pdf:pdf},
     issn = {20411723},
     journal = {Nature Communications},
     keywords = {Insulin signalling,Post,Proteomics,translational modifications},
     month = dec,
     number = {1},
     pages = {1--18},
     pmid = {31792197},
     publisher = {Nature Publishing Group},
     title = {{Global redox proteome and phosphoproteome analysis reveals redox switch in Akt}},
     url = {https://www.nature.com/articles/s41467-019-13114-4},
     volume = {10},
     year = {2019}
   }