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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2022 Papers

Z-⍺1-antitrypsin polymers impose molecular filtration in the endoplasmic reticulum after undergoing phase transition to a solid state. Chambers JE, Zubkov N, Kubánková M, Nixon-Abell J, Mela I, Abreu S, Schwiening M, Lavarda G, López-Duarte I, Dickens JA, Torres T., Kaminski CF, Holt LJ, Avezov E., Huntington JA, St George Hyslop P, Kuimova MK, Marciniak SJ. (2022). Science Advances 8:eabm2094. doi: 10.1126/sciadv.abm2094. PMID: 35394846.

Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant. Dickens JA, Rutherford E, Abreu S, Chambers JE, Ellis M, van Schadewijk A, Hiemstra P, Marciniak SJ (2022). Eur Respir J. 59: 2100267; doi: 10.1183/13993003.00267-2021. PMID: 34049951

Pharmacological targeting of endoplasmic reticulum stress in disease. Marciniak SJ, Chambers JE, Ron D (2022). Pharmacological targeting of endoplasmic reticulum stress in disease. Nat Rev Drug Discov. 21: 115-140. doi: 10.1038/s41573-021-00320-3. PMID: 34702991

Different cytokine patterns in BMPR2-mutation positive patients and pulmonary arterial hypertension patients without mutations and their influence on survival. Schwiening M, Swietlik E, Pandya D, Burling K, Barker P, Feng O, Treacy C, Abreu S, Wort S, Pepke-Zaba J, Gräf S, Marciniak SJ, Morrell N, Soon E (2022). Chest Jan 18:S0012-3692(22)00058-7. doi: 10.1016/j.chest.2022.01.019. [online ahead of print]. PMID: 35063447

Seventh BHD international symposium: recent scientific and clinical advancement. Woodford MR, Andreou A, Baba M, van de Beek I, Malta CD, Glykofridis I, Grimes H, Henske EP, Iliopoulos O, Kurihara M, Lazor R, Linehan WM, Matsumoto K, Marciniak SJ, Namba Y, Pause A, Rajan N, Ray A, Schmidt LS, Shi W, Steinlein OK, Thierauf J, Zoncu R, Webb A, Mollapour M. (2022) Oncotarget. 2022 13:173-181. doi: 10.18632/oncotarget.28176. eCollection 2022. PMID: 35070081

Combining clinical, radiological and genetic approaches to pneumothorax management. Grimes HL, Holden S, Babar J, Karia S, Wetscherek MTA, Barker A, Herre J, Knolle M, Maher ER, Genomics England Research Consortium and Marciniak SJ (2022). Combining clinical, radiological and genetic approaches to pneumothorax management. Thorax. 77(2):196-198. doi: thoraxjnl-2021-217210. PMID: 34145047

Meta-analysis of the association between emphysematous change on thoracic computerised tomography scan and recurrent pneumothorax. Girish M, Pharoah PD, Marciniak SJ (2022). Meta-analysis of the association between emphysematous change on thoracic computerised tomography scan and recurrent pneumothorax. QJM 115:215-221. doi: 10.1093/qjmed/hcab020. PMID: 33538832

2021 Papers

Catamenial pneumothorax. Kardaman N, Nizami M, Marciniak S, Hogan J, Aresu G (2021). Ann R Coll Surg Engl. 2021 Nov 26. doi: 10.1308/rcsann.2021.0164. [online ahead of print]. PMID: 34825583

Ambulatory thoracoscopic pleurodesis combined with indwelling pleural catheter in malignant pleural effusion. Foo CT, Pulimood T, Knolle M, Marciniak SJ, Herre J (2021). Front Surg. doi: 10.3389/fsurg.2021.738719. PMID: 34760917

A systematic review assessing the existence of pneumothorax-only variants of FLCN. Implications for lifelong surveillance of renal tumours. Matsumoto K, Lim D, Pharoah P, Maher E, Marciniak SJ (2021). Eur J Hum Genet 29(11):1595-1600. doi: 10.1038/s41431-021-00921-x. PMID: 34267338

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.  Evans RA, McAuley H, Harrison EM, Shikotra A, Singapuri A, Sereno M, Elneima O, Docherty AB, Lone NI, Leavy OC, Daines L, Baillie JK, Brown JS, Chalder T, De Soyza A, Diar Bakerly N, Easom N, Geddes JR, Greening NJ, Hart N, Heaney LG, Heller S, Howard L, Hurst JR, Jacob J, Jenkins RG, Jolley C, Kerr S, Kon OM, Lewis K, Lord JM, McCann GP, Neubauer S, Openshaw PJM, Parekh D, Pfeffer P, Rahman NM, Raman B, Richardson M, Rowland M, Semple MG, Shah AM, Singh SJ, Sheikh A, Thomas D, Toshner M, Chalmers JD, Ho LP, Horsley A, Marks M, Poinasamy K, Wain LV, Brightling CE; PHOSP-COVID Collaborative Group#. (2021). Lancet Respir Med. 9(11):1275-1287. doi: 10.1016/S2213-2600(21)00383-0. #Includes Marciniak S. PMID: 34627560

The Role of Unfolded Proteins in Lung Disease. Bradley KL, Stokes CA, Marciniak SJ*, Parker LC*, Condliffe AM* (2021). Thorax 76(1):92-99. doi: 10.1136/thoraxjnl-2019-213738. *Joint senior

A solution scan of societal options to reduce transmission and spread of respiratory viruses: SARS-CoV-2 as a case study. Sutherland WJ, Taylor NG, Aldridge DC, Martin P, Rhodes C, Shackelford G, Beard S, Belfield H, Bladon AJ, Brick C, Christie AP, Dobson AP, Downey H, Hood ASC, Hua F, Hughes AC, Jarvis RM, MacFarlane D, Morgan WH, Mupepele AC, Marciniak SJ, Nelson C, Ó hÉigeartaigh S, Rios Rojas C, Sainsbury KA, Smith RK, Sundaram LS, Thornton A, Watkins J, White TB, Willott K, Petrovan SO. J Biosaf Biosecur. 2021 Dec;3(2):84-90. doi: 10.1016/j.jobb.2021.08.003. Epub 2021 Sep 15. PMID: 34541465

Biological basis for novel mesothelioma therapies. Obacz J, Yung H, Shamseddin M, Linnane E, Liu X, Azad AA, Rassl DM, Fairen-Jimenez D, Rintoul RC, Nikolić MZ, Marciniak SJ. Br J Cancer. 2021 Oct;125(8):1039-1055. doi: 10.1038/s41416-021-01462-2. Epub 2021 Jul 5. PMID: 34226685

COVID-19 pneumothorax in the UK: a prospective observational study using the ISARIC WHO clinical characterisation protocol. Marciniak SJ, Farrell J, Rostron A, Smith I, Openshaw PJM, Baillie JK, Docherty A, Semple MG. Eur Respir J. 58:2100929 doi: 10.1183/13993003.00929-2021. PMID: 34083401

Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant. Dickens JA, Rutherford EN, Abreu S, Chambers JE, Ellis MO, van Schadewijk A, Hiemstra PS, Marciniak SJ. Eur Respir J. 2021 May 28:2100267. doi: 10.1183/13993003.00267-2021. Online ahead of print. PMID: 34049951

Development of a small molecule that corrects misfolding and increases secretion of Z α₁ -antitrypsin. Lomas DA, Irving JA, Arico-Muendel C, Belyanskaya S, Brewster A, Brown M, Chung CW, Dave H, Denis A, Dodic N, Dossang A, Eddershaw P, Klimaszewska D, Haq I, Holmes DS, Hutchinson JP, Jagger AM, Jakhria T, Jigorel E, Liddle J, Lind K, Marciniak SJ, Messer J, Neu M, Olszewski A, Ordonez A, Ronzoni R, Rowedder J, Rüdiger M, Skinner S, Smith KJ, Terry R, Trottet L, Uings I, Wilson S, Zhu Z, Pearce AC. EMBO Mol Med e13167 https://doi.org/10.15252/emmm.202013167. PMID: 33512066

2020 Papers

Role of unfolded proteins in lung disease. Bradley KL, Stokes CA, Marciniak SJ, Parker LC, Condliffe AM. Thorax. 2021 Jan;76(1):92-99. doi: 10.1136/thoraxjnl-2019-213738. Epub 2020 Oct 19. PMID: 33077618 Free PMC article.

The integrated stress response in pulmonary disease.Emanuelli G, Nassehzadeh-Tabriz N, Morrell NW, Marciniak SJ. Eur Respir Rev. 2020 Oct 1;29(157):200184. doi: 10.1183/16000617.0184-2020. Print 2020 Sep 30. PMID: 33004527 Free PMC article.

COVID-19 and pneumothorax: a multicentre retrospective case series. Martinelli AW, Ingle T, Newman J, Nadeem I, Jackson K, Lane ND, Melhorn J, Davies HE, Rostron AJ, Adeni A, Conroy K, Woznitza N, Matson M, Brill SE, Murray J, Shah A, Naran R, Hare SS, Collas O, Bigham S, Spiro M, Huang MM, Iqbal B, Trenfield S, Ledot S, Desai S, Standing L, Babar J, Mahroof R, Smith I, Lee K, Tchrakian N, Uys S, Ricketts W, Patel ARC, Aujayeb A, Kokosi M, Wilkinson AJK, Marciniak SJ. Eur Respir J. 2020 Nov 19;56(5):2002697. doi: 10.1183/13993003.02697-2020. Print 2020 Nov. PMID: 32907891.

Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma. Dell'Anno I, Barone E, Mutti L, Rassl DM, Marciniak SJ, Silvestri R, Landi S, Gemignani F. J Transl Med. 2020 Sep 4;18(1):341. doi: 10.1186/s12967-020-02487-6. PMID: 32887638.

HaloFlippers: A General Tool for the Fluorescence Imaging of Precisely Localized Membrane Tension Changes in Living Cells. Straková K, López-Andarias J, Jiménez-Rojo N, Chambers JE, Marciniak SJ, Riezman H, Sakai N, Matile S. ACS Cent Sci. 2020 Aug 26;6(8):1376-1385. doi: 10.1021/acscentsci.0c00666. Epub 2020 Jul 20. PMID: 32875078.

Pneumothorax and the biology of Birt-Hogg-Dubé syndrome.Marciniak SJ, Johnson SR. Thorax. 2020 Jun;75(6):442-443. doi: 10.1136/thoraxjnl-2020-214861. PMID: 32414881.

Susceptibility to cellular stress in PS1 mutant N2a cells is associated with mitochondrial defects and altered calcium homeostasis. Rojas-Charry L, Calero-Martinez S, Morganti C, Morciano G, Park K, Hagel C, Marciniak SJ, Glatzel M, Pinton P, Sepulveda-Falla D. Sci Rep. 2020 Apr 15;10(1):6455. doi: 10.1038/s41598-020-63254-7. PMID: 32296078.

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