Cell stress in lung 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

2023 Papers

BAP1 loss is associated with higher ASS1 expression in epithelioid mesothelioma: implications for therapeutic stratification. Barnett SE, Kenyani J, Tripari M, Butt Z, Grosman R, Querques F, Shaw L, Silva LC, Goate Z, Marciniak SJ, Rassl DM, Jackson R, Lian L-Y, Szlosarek PW, Sacco JJ, Coulson JM (2023). Mol Cancer Res doi: 10.1158/1541-7786.MCR-22-0635 [online ahead of print]. PMID: 36669126

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study. Jackson C, Stewart ID, Plekhanova T, Cunningham PS, Hazel AL, Al-Sheklly B, Aul R, Bolton CE, Chalder T, Chalmers JD, Chaudhuri N, Docherty AB, Donaldson G, Edwardson CL, Elneima O, Greening NJ, Hanley NA, Harris VC, Harrison EM, Ho LP, Houchen-Wolloff L, Howard LS, Jolley CJ, Jones MG, Leavy OC, Lewis KE, Lone NI, Marks M, McAuley HJC, McNarry MA, Patel BV, Piper-Hanley K, Poinasamy K, Raman B, Richardson M, Rivera-Ortega P, Rowland-Jones SL, Rowlands AV, Saunders RM, Scott JT, Sereno M, Shah AM, Shikotra A, Singapuri A, Stanel SC, Thorpe M, Wootton DG, Yates T, Gisli Jenkins R, Singh SJ, Man WD, Brightling CE, Wain LV, Porter JC, Thompson AAR, Horsley A, Molyneaux PL, Evans RA, Jones SE, Rutter MK, Blaikley JF; PHOSP-COVID Study Collaborative Group^#. (2023). Lancet Respir Med. 2023 Apr 14:S2213-2600(23)00124-8. doi: 10.1016/S2213-2600(23)00124-8. [online ahead of print]. ^#Includes Marciniak S PMID: 37072018

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study. McAuley HJC, Evans RA, Bolton CE, Brightling CE, Chalmers JD, Docherty AB, Elneima O, Greenhaff PL, Gupta A, Harris VC, Harrison EM, Ho LP, Horsley A, Houchen-Wolloff L, Jolley CJ, Leavy OC, Lone NI, Man WD, Marks M, Parekh D, Poinasamy K, Quint JK, Raman B, Richardson M, Saunders RM, Sereno M, Shikotra A, Singapuri A, Singh SJ, Steiner M, Tan AL, Wain LV, Welch C, Whitney J, Witham MD, Lord J, Greening NJ; PHOSP-COVID Study Collaborative Group^#. (2023). EClinicalMedicine. 2023 Mar 11;57:101896. doi: 10.1016/j.eclinm.2023.101896. eCollection 2023 Mar. ^#Includes Marciniak S. PMID: 36936404

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination. Liew F, Talwar S, Cross A, Willett BJ, Scott S, Logan N, Siggins MK, Swieboda D, Sidhu JK, Efstathiou C, Moore SC, Davis C, Mohamed N, Nunag J, King C, Thompson AAR, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho LP, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton DG, Dunachie S, Quint JK, Evans RA, Wain LV, Fontanella S, de Silva TI, Ho A, Harrison E, Baillie JK, Semple MG, Brightling C, Thwaites RS, Turtle L, Openshaw PJM; ISARIC4C Investigators; PHOSP-COVID collaborative group^# (2023). EBioMedicine. 2023 Jan;87:104402. doi: 10.1016/j.ebiom.2022.104402. Epub 2022 Dec 19. ^#Includes Marciniak S. PMID: 36543718

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

Catamenial pneumothorax. Kardaman N, Nizami M, Marciniak S, Hogan J, Aresu G (2021). Ann R Coll Surg Engl. 104(4):e109-e112. doi: 10.1308/rcsann.2021.0164. PMID: 34825583

The role of impulse oscillometry in the management of asthma when forced expiratory maneuvers are contraindicated: case series and literature review. Jordon LH, Gore RB, Rusk RA, Knox-Brown B, Marciniak SJ. J Asthma 59:1577-1583. doi: 10.1080/02770903.2021.1941088. PMID: 34112043

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. PHOSP-COVID Collaborative Group^#. (2022) Lancet Respir Med. 10:761-775. doi: 10.1016/S2213-2600(22)00127-8. ^#Includes Marciniak S. PMID: 35472304.

Large scale clinical trials - lessons from the COVID-19 pandemic. Horsley A, Pearmain L, Knight S, Schindler N, Wang R, Bennett M, Robey RC, Davies JC, Djukanovic R, Heaney LG, Hussell T, Marciniak SJ, McGarvey L, Porter JC, Wilkinson T, Brightling C, Ho L-P (2022). BMJ Open Respiratory Research 2022;9:doi: 10.1136/bmjresp-2022-001226 PMID: 35701071

Full-length antithrombim frameshift variant with aberrant C-terminus causes endoplasmic reticulum retention with a dominant-negative effect. Bravo-Pérez C, Toderici M, Chambers JE, Martínez-Menárguez JA, Garrido-Rodriguez P, Pérez-Sanchez H, Morena-Barrio B, Padilla J, Miñano A, Cifuentes-Riquelme R, Vicente V, Lozano ML, Marciniak SJ, de la Morena-Barrio ME, Corral J (2022). JCI Insight 7(19):e161430. doi: 10.1172/jci.insight.161430. PMID: 36214221

2021 Papers

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

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

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