Imperial College London

ProfessorSunilShaunak

Faculty of MedicineDepartment of Infectious Disease

Emeritus Professor in Infectious Diseases
 
 
 
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Contact

 

s.shaunak Website

 
 
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Location

 

8.N15Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

103 results found

Monnery BD, Wright M, Cavill R, Hoogenboom R, Shaunak S, Steinke JHG, Thanou Met al., 2017, Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity, INTERNATIONAL JOURNAL OF PHARMACEUTICS, Vol: 521, Pages: 249-258, ISSN: 0378-5173

Journal article

Armstrong-James DPH, 2016, Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death, American Journal of Respiratory and Critical Care Medicine, Vol: 194, Pages: 1127-1139, ISSN: 1535-4970

Rationale: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis.Objectives: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants.Methods: We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies.Measurements and Main Results: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell–cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape.Conclusions: These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.

Journal article

Czaplewski L, Bax R, Clokie M, Dawson M, Fairhead H, Fischetti VA, Foster S, Gilmore BF, Hancock REW, Harper D, Henderson IR, Hilpert K, Jones BV, Kadioglu A, Knowles D, Olafsdottir S, Payne D, Projan S, Shaunak S, Silverman J, Thomas CM, Trust TJ, Warn P, Rex JHet al., 2016, Alternatives to antibiotics-a pipeline portfolio review, LANCET INFECTIOUS DISEASES, Vol: 16, Pages: 239-251, ISSN: 1473-3099

Journal article

Shaunak S, 2015, Perspective: Dendrimer drugs for infection and inflammation, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 468, Pages: 435-441, ISSN: 0006-291X

Journal article

Shah A, Kannambath S, Herbst S, Rogers A, Carby M, Reed A, Mostowy S, Shaunak S, Armstrong-James Det al., 2015, 'THE KISS OF DEATH' - CALCINEURIN INHIBITORS PREVENT ACTIN-DEPENDENT LATERAL TRANSFER OF ASPERGILLUS FUMIGATUS IN NECROPTOTIC HUMAN MACROPHAGES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A48-A48, ISSN: 0040-6376

Conference paper

Singanayagam A, Lamb L, Makinde JE, Teo I, Shaunak Set al., 2015, Systemic cytokine storm in severe eosinophilic dermatitis, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, Vol: 108, Pages: 907-908, ISSN: 1460-2725

Journal article

Islam D, Lombardini E, Ruamsap N, Imerbsin R, Khantapura P, Teo I, Neesanant P, Gonwong S, Yongvanitchit K, Swierczewski BE, Mason CJ, Shaunak Set al., 2015, Controlling the cytokine storm in severe bacterial diarrhoea with an oral Toll-like receptor 4 antagonist, Immunology, Vol: 147, Pages: 178-189, ISSN: 0019-2805

Shigella dysenteriae causes the most severe of all infectious diarrheas and colitis. We infected rhesus macaques orally and also treated them orally with a small and non-absorbable polypropyletherimine dendrimer glucosamine (DG) that is a Toll Like Receptor-4 antagonist. Antibiotics were not given for this life threatening infection. Six days later, the clinical score for diarrhea, mucus and blood was 54% lower, colon IL-8 and IL-6 were both 77% lower, and colon neutrophil infiltration was 75% less. Strikingly, vasculitis did not occur and tissue fibrin thrombi were reduced by 67%. There was no clinical toxicity or adverse effect of DG on systemic immunity. This is the first report in nonhuman primates of the therapeutic efficacy of a small and orally bioavailable TLR antagonist in severe infection. Our results show that an oral TLR4 antagonist can enable controlled resolution of the infection-related-inflammatory response and can also prevent neutrophil-mediated gut wall necrosis in severe infectious diarrheas.

Journal article

Shirkhani K, Teo I, Armstrong-James D, Shaunak Set al., 2015, Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis, NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, Vol: 11, Pages: 1217-1226, ISSN: 1549-9634

Journal article

Monnery BD, Shaunak S, Thanou M, Steinke JHGet al., 2015, Improved Synthesis of Linear Poly(ethylenimine) via Low-Temperature Polymerization of 2-Isopropyl-2-oxazoline in Chlorobenzene, MACROMOLECULES, Vol: 48, Pages: 3197-3206, ISSN: 0024-9297

Journal article

Shah A, Abdolrasouli A, Soresi S, Herbst S, Reed A, Carby M, Thornton CR, Drumright L, Shaunak S, Armstrong-James Det al., 2015, The Utility of Novel Multi-Stage Testing for the Diagnosis of Pulmonary Aspergillosis in a Cohort of Lung Transplant Recipients, 35th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation, Publisher: ELSEVIER SCIENCE INC, Pages: S306-S306, ISSN: 1053-2498

Conference paper

Herbst S, Shah A, Moya MM, Marzola V, Jensen B, Reed A, Birrell MA, Saijo S, Mostowy S, Shaunak S, Armstrong-James Det al., 2015, Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus, EMBO Molecular Medicine, Vol: 7, Pages: 240-258, ISSN: 1757-4676

Transplant recipients on calcineurin inhibitors are at high risk of invasive fungal infection. Understanding how calcineurin inhibitors impair fungal immunity is a key priority for defining risk of infection. Here, we show that the calcineurin inhibitor tacrolimus impairs clearance of the major mould pathogen Aspergillus fumigatus from the airway, by inhibiting macrophage inflammatory responses. This leads to defective early neutrophil recruitment and fungal clearance. We confirm these findings in zebrafish, showing an evolutionarily conserved role for calcineurin signalling in neutrophil recruitment during inflammation. We find that calcineurin–NFAT activation is phagocytosis dependent and collaborates with NF‐κB for TNF‐α production. For yeast zymosan particles, activation of macrophage calcineurin–NFAT occurs via the phagocytic Dectin‐1–spleen tyrosine kinase pathway, but for A. fumigatus, activation occurs via a phagosomal TLR9‐dependent and Bruton's tyrosine kinase‐dependent signalling pathway that is independent of MyD88. We confirm the collaboration between NFAT and NF‐κB for TNF‐α production in primary alveolar macrophages. These observations identify inhibition of a newly discovered macrophage TLR9–BTK–calcineurin–NFAT signalling pathway as a key immune defect that leads to organ transplant‐related invasive aspergillosis.

Journal article

Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppinen A, Cotsapas C, Shah TS, Spencer C, Booth D, Goris A, Oturai A, Saarela J, Fontaine B, Hemmer B, Martin C, Zipp F, D'Alfonso S, Martinelli-Boneschi F, Taylor B, Harbo HF, Kockum I, Hillert J, Olsson T, Ban M, Oksenberg JR, Hintzen R, Barcellos LF, Agliardi C, Alfredsson L, Alizadeh M, Anderson C, Andrews R, Sondergaard HB, Baker A, Band G, Baranzini SE, Barizzone N, Barrett J, Bellenguez C, Bergamaschi L, Bernardinelli L, Berthele A, Biberacher V, Binder TMC, Blackburn H, Bomfim IL, Brambilla P, Broadley S, Brochet B, Brundin L, Buck D, Butzkueven H, Caillier SJ, Camu W, Carpentier W, Cavalla P, Celius EG, Coman I, Comi G, Corrado L, Cosemans L, Cournu-Rebeix I, Cree BAC, Cusi D, Damotte V, Defer G, Delgado SR, Deloukas P, di Sapio A, Dilthey AT, Donnelly P, Dubois B, Duddy M, Edkins S, Elovaara I, Esposito F, Evangelou N, Fiddes B, Field J, Franke A, Freeman C, Frohlich IY, Galimberti D, Gieger C, Gourraud P-A, Graetz C, Graham A, Grummel V, Guaschino C, Hadjixenofontos A, Hakonarson H, Halfpenny C, Hall G, Hall P, Hamsten A, Harley J, Harrower T, Hawkins C, Hellenthal G, Hillier C, Hobart J, Hoshi M, Hunt SE, Jagodic M, Jelcic I, Jochim A, Kendall B, Kermode A, Kilpatrick T, Koivisto K, Konidari I, Korn T, Kronsbein H, Langford C, Larsson M, Lathrop M, Lebrun-Frenay C, Lechner-Scott J, Lee MH, Leone MA, Leppa V, Liberatore G, Lie BA, Lill CM, Linden M, Link J, Luessi F, Lycke J, Macciardi F, Mannisto S, Manrique CP, Martin R, Martinelli V, Mason D, Mazibrada G, McCabe C, Mero I-L, Mescheriakova J, Moutsianas L, Myhr K-M, Nagels G, Nicholas R, Nilsson P, Piehl F, Pirinen M, Price SE, Quach H, Reunanen M, Robberecht W, Robertson NP, Rodegher M, Rog D, Salvetti M, Schnetz-Boutaud NC, Sellebjerg F, Selter RC, Schaefer C, Shaunak S, Shen L, Shields S, Siffrin V, Slee M, Sorensen PS, Sorosina M, Sospedra M, Spurkland A, Strange A, Sundqvist E, Thijs V, Thorpe J, Ticca A, Tienari P, van Duijn C, Visser EM, Vucic Set al., 2013, Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis, NATURE GENETICS, Vol: 45, Pages: 1353-+, ISSN: 1061-4036

Journal article

Shah A, Herbst S, Kannambath S, Carby M, Shaunak S, Armstrong-James Det al., 2013, CALCINEURIN INHIBITORS IMPAIR THE HOST INNATE IMMUNE RESPONSE TO INVASIVE ASPERGILLOSIS LIKELY DUE TO A CALCINEURIN-DEPENDANT DEFECT IN FUNGAL KILLING IN ALVEOLAR MACROPHAGES, JOURNAL OF INFECTION, Vol: 67, Pages: 343-344, ISSN: 0163-4453

Journal article

Herbst S, Shah A, Carby M, Chusney G, Kikkeri N, Dorling A, Bignell E, Shaunak S, Armstrong-James Det al., 2013, A new and clinically relevant murine model of solid-organ transplant aspergillosis, DISEASE MODELS & MECHANISMS, Vol: 6, Pages: 643-651, ISSN: 1754-8403

Journal article

Armstrong-James D, Teo I, Herbst S, Petrou M, Shiu KY, McLean A, Taube D, Dorling A, Shaunak Set al., 2012, Renal Allograft Recipients Fail to Increase Interferon-gamma During Invasive Fungal Diseases, AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 12, Pages: 3437-3440, ISSN: 1600-6135

Journal article

Teo I, Toms SM, Marteyn B, Barata TS, Simpson P, Johnston KA, Schnupf P, Puhar A, Bell T, Tang C, Zloh M, Matthews S, Rendle PM, Sansonetti PJ, Shaunak Set al., 2012, Preventing acute gut wall damage in infectious diarrhoeas with glycosylated dendrimers, EMBO MOLECULAR MEDICINE, Vol: 4, Pages: 866-881, ISSN: 1757-4676

Journal article

Morris TC, Moore LSP, Shaunak S, 2012, MOBILE PHONES: UNHELPFUL APPS Doctors taking a pulse using their mobile phone can spread MRSA, BRITISH MEDICAL JOURNAL, Vol: 344, ISSN: 0959-535X

Journal article

Barata T, Teo I, Lalwani S, Simanek E, Zloh M, Shaunak Set al., 2011, Computational design principles for bioactive dendrimer based constructs as antagonists of the TLR4-MD-2-LPS complex, BIOMATERIALS, Vol: 32, Pages: 8702-8711, ISSN: 0142-9612

Journal article

Corware K, Harris D, Teo I, Rogers M, Naresh K, Mueller I, Shaunak Set al., 2011, Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid, BIOMATERIALS, Vol: 32, Pages: 8029-8039, ISSN: 0142-9612

Journal article

Barata TS, Brocchini S, Teo I, Shaunak S, Zloh Met al., 2011, From sequence to 3D structure of hyperbranched molecules: application to surface modified PAMAM dendrimers, JOURNAL OF MOLECULAR MODELING, Vol: 17, Pages: 2741-2749, ISSN: 1610-2940

Journal article

Monnery B, Shaunak S, Thanou M, Steinke JHGet al., 2011, Monodisperse 1-PEI: A route to the optimum polymer transfectant?, Publisher: MARY ANN LIEBERT INC, Pages: A90-A91, ISSN: 1043-0342

Conference paper

Barata TS, Shaunak S, Teo I, Zloh M, Brocchini Set al., 2011, Structural studies of biologically active glycosylated polyamidoamine (PAMAM) dendrimers, JOURNAL OF MOLECULAR MODELING, Vol: 17, Pages: 2051-2060, ISSN: 1610-2940

Journal article

Barata TS, Teo I, Brocchini S, Zloh M, Shaunak Set al., 2011, Partially Glycosylated Dendrimers Block MD-2 and Prevent TLR4-MD-2-LPS Complex Mediated Cytokine Responses, PLOS COMPUTATIONAL BIOLOGY, Vol: 7, ISSN: 1553-734X

Journal article

Karina C, Matthew R, Ian T, Naresh K, Ingrid M, Sunil Set al., 2010, A COST-EFFECTIVE CURE FOR CUTANEOUS LEISHMANIASIS, JOURNAL OF INFECTION, Vol: 61, Pages: 522-523, ISSN: 0163-4453

Journal article

Corware KD, Rogers M, Teo I, Muller I, Shaunak Set al., 2010, An amphotericin B-based drug for treating experimental Leishmania major infection, Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 104, Pages: 749-750

There is an urgent need for a non-toxic and low-cost treatment for cutaneous leishmaniasis. We synthesised and tested in vivo an amphotericin B-poly(methacrylic acid) drug (AmB-PMA) that had previously shown in-vitro activity against Leishmania major and L. donovani parasites. Efficacy was determined using L. major footpad infection in 30 non-healing BALB/c mice. Three subcutaneous injections of AmB-PMA at days 7, 14 and 21 post-infection resulted in a reduction of ∼80% in lesion size by day 35 post-infection in 18 treated mice compared with six untreated controls, and complete healing of lesions by day 50 with no lesion relapse seen at day 80 post-infection in six treated mice. Healing was associated with decreased IL-10 (P=0.002) and increased IFN-γ (P=0.005) in the footpad.

Journal article

Barata TS, Brocchini S, Teo I, Shaunak S, Zloh Met al., 2010, Structural Studies on Glycosylated PAMAM Dendrimers, JOURNAL OF PHARMACY AND PHARMACOLOGY, Vol: 62, Pages: 1371-1372, ISSN: 0022-3573

Journal article

Armstrong-James D, Teo IA, Shrivastava S, Petrou MA, Taube D, Dorling A, Shaunak Set al., 2010, Exogenous Interferon-gamma Immunotherapy for Invasive Fungal Infections in Kidney Transplant Patients, AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 10, Pages: 1796-1803, ISSN: 1600-6135

Journal article

Lalwani S, Chouai A, Perez LM, Santiago V, Shaunak S, Simanek EEet al., 2009, Mimicking PAMAM Dendrimers with Amphoteric, Hybrid Triazine Dendrimers: A Comparison of Dispersity and Stability, MACROMOLECULES, Vol: 42, Pages: 6723-6732, ISSN: 0024-9297

Journal article

Lalwani S, Venditto VJ, Chouai A, Rivera GE, Shaunak S, Simanek EEet al., 2009, Electrophoretic Behavior of Anionic Triazine and PAMAM Dendrimers: Methods for Improving Resolution and Assessing Purity Using Capillary Electrophoresis, MACROMOLECULES, Vol: 42, Pages: 3152-3161, ISSN: 0024-9297

Journal article

Brocchini S, Godwin A, Balan S, Choi J-W, Zloh M, Shaunak Set al., 2008, Disulfide bridge based PEGylation of proteins, ADVANCED DRUG DELIVERY REVIEWS, Vol: 60, Pages: 3-12, ISSN: 0169-409X

Journal article

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