Endoplasmic reticulum stress in disease

Proteins destined for secretion or for insertion into the cell membrane are first folded within the endoplasmic reticulum.  The process of protein folding can become defective in many disease states such as hypoxia, malignancy and some forms of diabetes.  When the level of misfolded proteins within the endoplasmic reticulum increases, the cell is said to experience “endoplasmic reticulum stress”.

We wish to understand the cellular consequences of endoplasmic reticulum stress; in particular its effects on tissue growth and cell survival.  In doing so, we hope to identify targets for the development of novel therapies.

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Selected References

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2015 Papers


Virulence factors of Pseudomonas aeruginosa induce both the unfolded protein and integrated stress responses in airway epithelial cells.

van ‘t Wout E.F.A., van Schadewijk A., van Boxtel R., Dalton L.E., Clarke H.J., Tommassen J., Marciniak S.J.*, Hiemstra P.S.* (2015). ­­PLoS Pathogens 11(6): e1004946. doi:10.1371/journal.ppat.1004946

*Joint senior authors

Actin dynamics tune the integrated stress response by regulatins eukaryotic initiation factor 2α dephosphorylation.

Chambers, J.E., Dalton, L.E., Clarke, H.J., Malzer, E., Dominicus, C.S., Patel, V., Moorhead, G.B.G., Ron, D., and Marciniak, S.J. (2015). eLIFE doi.org/10.7554/eLife.04872.

G-actin provides substrate-specificity to eukaryotic initiation factor 2a holophosphatase.

Chen, R., Rato, C., Yan, Y., Crespillo-Casado, A., Clarke, H.J., Harding, H.P., Marciniak, S.J. *, Read, R.J. *, and Ron, D*. (2015). eLIFE doi.org/10.7554/eLife.04871.

*Joint senior authors

Non-interventional statistical comparison of BTS and CHEST guidelines for size and severity in primary pneumothorax.

Nikolic M.Z., Lok L.S.C., Mattishent K., Barth S., Yung B., Cummings N., Wade D., Vali Y., Chong K., Wilkinson A., Mikolasch T., Brij S., Jenkins H.S., Kamath A., Pasteur M., Hopkins T., Wason J., Marciniak S.J. (2015) Eur. Respir. J. 45: 1731-4.

A single-chain variable fragment intrabody prevents intracellular polymerisation of Z alpha1-antitrypsin while allowing its antiproteinase activity.

Ordóñez A., Pérez J., Tan L., Dickens J.A., Motamedi-Shad N., Irving J.A., Haq I., Ekeowa U., Marciniak S.J., Miranda E., Lomas D.A. (2015) FASEB J. 29:2667-78.

Characterising the association of latency with α(1)-antitrypsin polymerisation using a novel monoclonal antibody.

Tan L., Perez J., Mela M., Miranda E., Burling K.A., Rouhani F.N., DeMeo D.L., Haq I., Irving J.A., Ordonez A., Dickens J.A., Brantly M., Marciniak S.J., Alexander G., Gooptu B., Lomas D.A., (2015) Int J Biochem Cell Biol. 58:81-91.

Function of monocytes and monocyte-derived macrophages in α1-antitrypsin deficiency.

van ‘t Wout E.F.A., van Schadewijk A., Lomas D.A., Stolk J, Marciniak S.J., Hiemstra P.S. (2015). Eur. Respir. J. 45: 3654-376.


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