Professor Stefan Marciniak

Subject: Medicine
Proteins must be folded properly to function. If this becomes defective, cells experience stress and respond by clearing away these misfolded proteins for destruction. My lab investigates how the response to this form a cellular stress is important in health and disease. Current projects in our group address a variety of lung diseases including mesothelioma, pulmonary hypertension, and pulmonary fibrosis.

My clinical research focuses on pneumothorax (punctured lungs) and how it can be caused by defective genes or by infections including COVID-19.

Director of Studies in Clinical Medicine
Professor of Respiratory Science; Director of the Cambridge MB/PhD Programme; Principal Investigator, Cambridge Institute for Medical Research (CIMR)

I studied medicine at the University of Cambridge as part of its MB/PhD Programme. After medical posts in Cambridge, London and Edinburgh, I undertook post-doctoral training in New York funded by the Wellcome Trust and as an MRC Clinician Scientist Fellow back in Cambridge. I established my own group in CIMR as an MRC Senior Clinical Research Fellow in 2012.  I am now Professor of Respiratory Science at the University of Cambridge and an Honorary Consultant Respiratory Physician at Addenbrooke’s and Royal Papworth Hospitals. My laboratory research focuses on the role of stress signalling in lung disease.  My clinical research focuses on pleural medicine, especially the genetics of pneumothorax. I am Director of the University of Cambridge MB/PhD Programme.

Selection from

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. Science Advances 2022; 8:eabm2094. doi: 10.1126/sciadv.abm2094. PMID: 35394846.

Pharmacological targeting of endoplasmic reticulum stress in disease. Marciniak SJ, Chambers JE, Ron D. Nature Review Drug Discovery. 2021 Oct 26. doi: 10.1038/s41573-021-00320-3. Online ahead of print. PMID: 34702991.

Combining clinical, radiological and genetic approaches to pneumothorax management. Grimes HL, Holden S, Babar J, Karia S, Wetscherek MT, Barker A, Herre J, Knolle MD, Maher ER; Genomics England Research Consortium, Marciniak SJ. Thorax. 2021 Jun 18:thoraxjnl-2021-217210. doi: 10.1136/thoraxjnl-2021-217210. Online ahead of print. PMID: 34145047

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. 2021 Sep 16;58(3):2100929. doi: 10.1183/13993003.00929-2021. Print 2021 Sep. 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

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.

An Optical Technique for Mapping Microviscosity Dynamics in Cellular Organelles. Chambers J.E., Kubankova M., Huber, R., López-Duart I, Avezov E., Bond P., Marciniak S.J.*, Kuimova, M.* (2018). ACS Nano. doi: 10.1021/acsnano.8b00177 [Epub ahead of print] *Joint senior authors

G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases.
Chen R, Rato C, Yan Y, Crespillo-Casado A, Clarke HJ, Harding HP, Marciniak SJ*, Read RJ*, Ron D*. Elife. 2015 Mar 16;4:e04871. doi: 10.7554/eLife.04871. PMID: 25774600 Free PMC article. *Joint corresponding authors

Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation. Chambers JE, Dalton LE, Clarke HJ, Malzer E, Dominicus CS, Patel V, Moorhead G, Ron D, Marciniak SJ. Elife. 2015 Mar 16;4:e04872. doi: 10.7554/eLife.04872. PMID: 25774599

An Optical Technique for Mapping Microviscosity Dynamics in Cellular Organelles. Chambers J.E., Kubankova M., Huber, R., López-Duart I, Avezov E., Bond P., Marciniak S.J.*, Kuimova, M.* (2018) ACS Nano 12:4398-4407. *Joint senior authors

The integrated stress response regulates BMP signalling through effects on translation. Malzer E., Dominicus C.S., Chambers J.E., Dickens J.A., Mookerjee S., Marciniak S.J. (2018). BMC Biology 16:34

Familial pneumothorax – towards precision medicine. Scott R.M., Henske E.P., Raby B., Boone P.M., Rusk R.A., Marciniak S.J. (2018). Thorax 73:270-276.

The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-α1-antitrypsin. Dickens J.A., Ordóñez A., Chambers J.E., Beckett A.J., Patel V., Malzer E., Dominicus C.S., Bradley J., Peden A.A., Prior I.A., Lomas D.A., Marciniak S.J. (2016). FASEB J 30: 4083-4097.

Spontaneous pneumothorax can be associated with TGFBR2 mutation. Chambers J.E., Dalton L.E., Subramanian D.N., Gooptu B., Balan A., Park S-P., Holden S., Marciniak S.J. (2015). Eur. Respir. J. 46: 1832-1835.

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 regulating 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

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 *Joint senior authors

Honorary Consultant Physician, Cambridge University Hospitals
Honorary Consultant Physician, Royal Papworth Hospital
Director of the NHS England Rare Disease Collaborative Network (RDCN) in Familial Pneumothorax
Lead for Familial Pneumothorax, Respiratory Genomics England Clinical Interpretation Partnership (GeCIP)
Chair, Mesothelioma UK’s Research and Audit Scientific Committee
Fellow of the Royal College of Physicians