Contact

Group Lead
Professor George Hanna
g.hanna@imperial.ac.uk

What we do

Our research focuses on the role of volatile organic compounds (VOCs) as non-invasive markers of human disease. VOCs are small molecules that are produced by the body and released via the breath, urine, stool and skin. Variation in their levels is associated with a number of diseases, including cancer.

VOC analysis in breath has been the major focus of our research owing to universal acceptability amongst patients of all backgrounds. We have conducted a number of large clinical trials examining the performance of breath testing for the detection of oesophagogastric, colorectal and pancreatic cancers. To support the wider of adoption of breath testing in clinical practice we have developed quality-controlled protocols for breath collection and handling in clinical practice to ensure findings are accurate and reproducible. Parallel research is also being conducted to understand the origin and mechanisms of VOC release from healthy and cancer patients. Our laboratory is equipped with state-of-the-art mass spectrometry instruments that are able to reliably detect VOCs levels up to 1 part per billion (1:1000,000,000).

Why it is important

At an early stage many cancers, including those affecting the gastrointestinal tract, often have non-specific symptoms. For example, symptoms such are heartburn and indigestion are common to many benign (non-cancer) conditions, but in a minority of patients may signify early stomach or oesophageal cancer. When patients present to medical attention with such symptoms it can be difficult for healthcare professionals to decide if further testing is necessary. Many existing tests for diagnosing cancer are invasive and expensive, meaning that it is difficult to justify their use in the majority of patients who will not have cancer. Consequently, for many patients with early cancers, further investigation is delayed until symptoms become more apparent. At this point the tumour is more likely to be at an advanced, incurable, stage.

Our goal is to develop a novel breath test, for use in primary care patients with gastrointestinal symptoms who are at risk of cancer, to determine which patients would benefit from further definitive investigation. In achieving this we hope to improve cancer survival through earlier detection.

How it can benefit patients

Our research intends to make investigation of early cancer symptoms more accessible to patients. By detecting cancers earlier, we will be able to improve patient survival. For the NHS and other healthcare systems the test will provide an accurate, affordable and acceptable solution for early cancer detection.

Summary of current research

The groups research is divided between three core themes.

Clinical trials in disease detection through VOC analysis

We have conducted large scale clinical trials of breath analysis for the detection of gastroesophageal, colorectal and pancreatic cancers recruiting over 4000 patients. We also performed a large-scale trial examining the feasibility of different recruitment and engagement strategies for breath testing in primary care. We will start recruitment to major trials enrolling more than 10,000 symptomatic patients at risk of oesophagogastric (AROMA trial) and colorectal (COBRA II trial) cancers.

Studies to determine the biology and mechanisms of VOC production and release

Our group has undertaken extensive work to understand the molecular and genetic drivers of VOC production in cancer. We have also studied factors influencing the release of VOCs from different sites within the body in order to better understand optimal approaches to their detection. Our current research focuses on the role of the cancer associated microbiome in VOC production.

Methodologies for high throughput and quality-controlled VOC analysis

We maintain a strong focus on establishing accurate and reliable methods for VOC detection in clinical practice. We have developed and optimised methods for VOC analysis in breath, urine and other biofluids. In establishing those methods, we have sought to minimise sample losses and contamination that can occur at all points of the analytical pathway. We also developed a machine learning platform for analysis of VOC data that has overcome the challenges of large-scale data processing in breath analysis and enabled molecular network analysis. The next step will be to acquire ISO accreditation for our laboratory in preparation for large-scale breath testing in clinical practice.

Additional information

Collaborators

Internal

External
  • Professor Lesley Hoyles (University of Nottingham)
  • Professor Patrik Spanel (J. Heyrovský Institute of Physical Chemistry)

PhD students

  • Miss Sara Jamel
  • Miss Bhamini Vadhwana
  • Miss Yan Mei Goh
  • Dr Georgia Woodfield
  • Dr Qing Wen
  • Dr Michael Hewett
  • Mr Bibek Das
  • Mr Munir Tarazi
  • Miss Anuja Mitra

Publications

  1. Antonowicz S, Bodai Z, Wiggins T, Markar SR, Boshier PR, Adam M, Lu H, Kudo H, Rosini F, Goldin R, Moralli D, Green K, Habib N, Gabra H, Fitzgerald R, Takats Z, Hanna GB. Endogenous aldehyde accumulation generates genotoxicity and exhaled biomarkers in esophageal adenocarcinoma. Nature communication 2021 [In press].
  2. Belluomo I, Boshier PR, Myridakis A, Vadhwana B, Markar SR, Spanel P, Hanna GB. Selected ion flow tube mass spectrometry (SIFT-MS) for targeted analysis of volatile organic compounds in human breath. Nature Protocols 2021 [In press].
  3. Aksenov A, Laponogov I, Zhang Z, Doran S, Belluomo I, Veselkov D, Bittremieux W, Nothias L, Nothias-Esposito M, Maloney K, Misra B, Melnik A, Jones K, Dorrestein K, Panitchpakdi M, Ernst M, van der Hooft J, Gonzalez M, C. C, Amézquita A, Callewaert, Morton J, Quinn R, Bouslimani A, Orio A, Petras D, Smania A, Couvillion S, Burnet M, Nicora C, Zink E, Metz T, Artaev V, Humston-Fulmer E, Gregor R, Meijler M, Mizrahi I, Eyal S, Anderson B, Dutton R, Lugan R, Le Boulch P, Guitton Y, Prevost S, Poirier A, Dervilly G, Le Bizec B, Fait A, Persi N, Song C, Gashu K, Coras R, Guma M, Manasson J, Scher J, Barupal D, Alseekh S, Fernie A, Mirnezami R, Vasiliou V, Schmid R, Borisov R, Kulikova L, Knight R, Wang M, Hanna GB, Dorrestein P, Veselkov K. Algorithmic Learning for Auto-deconvolution of GC-MS Data to Enable Molecular Networking within GNPS. Nature Biotechnology 2020:https://doi.org/10.1101/2020.01.13.905091.
  4. Abbassi-Ghadi N, Antonowicz S, McKenzie J, Kumar S, Huang J, Jones E, Strittmatter N, Petts G, Kudo H, court S, Hoare J, Veselkov K, Goldin R, Takats Z, Hanna G. De Novo Lipogenesis Alters the Phospholipidome of Esophageal Adenocarcinoma. Cancer Res. 2020 Jul 1;80(13):2764–74.
  5. Vadhwana B, Belluomo I, Boshier PR, Pavlou C, Španěl P, Hanna GB. Impact of oral cleansing strategies on exhaled volatile organic compound levels. Rapid Commun Mass Spectrom. 2020 May 15;34(9).
  6. Goh YM, Antonowicz SS, Boshier P, Hanna GB. Metabolic Biomarkers of Squamous Cell Carcinoma of the Aerodigestive Tract: A Systematic Review and Quality Assessment. Oxid Med Cell Longev. 2020;2020.
  7. Markar SR, Chin ST, Romano A, Wiggins T, Antonowicz S, Paraskeva P, Ziprin P, Darzi A, Hanna GB. Breath Volatile Organic Compound Profiling of Colorectal Cancer Using Selected Ion Flow-tube Mass Spectrometry. Ann Surg. 2019;269(5):903-10.
  8. Hanna GB, Boshier PR, Markar SR, Romano A. Accuracy and Methodologic Challenges of Volatile Organic Compound-Based Exhaled Breath Tests for Cancer Diagnosis: A Systematic Review and Meta-analysis. JAMA Oncol. 2019;5(1):e182815.
  9. Adam ME, Fehervari M, Boshier PR, Chin ST, Lin GP, Romano A, Kumar S, Hanna GB. Mass-Spectrometry Analysis of Mixed-Breath, Isolated-Bronchial-Breath, and Gastric-Endoluminal-Air Volatile Fatty Acids in Esophagogastric Cancer. Anal Chem. 2019;91(5):3740-6.
  10. Romano A, Hanna GB. Identification and quantification of VOCs by proton transfer reaction time of flight mass spectrometry: An experimental workflow for the optimization of specificity, sensitivity, and accuracy. J Mass Spectrom. 2018;53(4):287-95.
  11. Romano A, Doran S, Belluomo I, Hanna GB. High-Throughput Breath Volatile Organic Compound Analysis Using Thermal Desorption Proton Transfer Reaction Time-of-Flight Mass Spectrometry. Anal Chem. 2018;90(17):10204-10.
  12. Markar SR, Wiggins T, Antonowicz S, Chin ST, Romano A, Nikolic K, Evans B, Cunningham D, Mughal M, Lagergren J, Hanna GB. Assessment of a Noninvasive Exhaled Breath Test for the Diagnosis of Oesophagogastric Cancer. JAMA Oncol. 2018;4(7):970-6.
  13. Markar SR, Brodie B, Chin ST, Romano A, Spalding D, Hanna GB. Profile of exhaled-breath volatile organic compounds to diagnose pancreatic cancer. Br J Surg. 2018;105(11):1493-500.
  14. Chin ST, Romano A, Doran SLF, Hanna GB. Cross-platform mass spectrometry annotation in breathomics of oesophageal-gastric cancer. Sci Rep. 2018;8(1):5139.
  15. Boshier PR, Fehervari M, Markar SR, Purkayastha S, Spanel P, Smith D, Hanna GB. Variation in Exhaled Acetone and Other Ketones in Patients Undergoing Bariatric Surgery: a Prospective Cross-sectional Study. Obes Surg. 2018;28(8):2439-46.
  16. Doran SLF, Romano A, Hanna GB. Optimisation of sampling parameters for standardised exhaled breath sampling. J Breath Res. 2017;12(1):016007.
  17. Boshier PR, Knaggs AL, Hanna GB, Marczin N. Perioperative changes in exhaled nitric oxide during oesophagectomy. J Breath Res. 2017;11(4):047109.
  18. Pabary R, Huang J, Kumar S, Alton EW, Bush A, Hanna GB, Davies JC. Does mass spectrometric breath analysis detect Pseudomonas aeruginosa in cystic fibrosis? Eur Respir J. 2016;47(3):994-7.
  19. Abbassi-Ghadi N, Golf O, Kumar S, Antonowicz S, McKenzie JS, Huang J, Strittmatter N, Kudo H, Jones EA, Veselkov K, Goldin R, Takats Z, Hanna GB. Imaging of Esophageal Lymph Node Metastases by Desorption Electrospray Ionization Mass Spectrometry. Cancer Res. 2016 Oct 1;76(19):5647-5656.
  20. Abbassi-Ghadi N, Jones EA, Gomez-Romero M, Golf O, Kumar S, Huang J, Kudo H, Goldin RD, Hanna GB, Takats Z. A Comparison of DESI-MS and LC-MS for the Lipidomic Profiling of Human Cancer Tissue. J Am Soc Mass Spectrom. 2016;27(2):255-64.
  21. Markar SR, Wiggins T, Kumar S, Hanna GB. Exhaled breath analysis for the diagnosis and assessment of endoluminal gastrointestinal diseases. J Clin Gastroenterol. 2015;49(1):1-8.
  22. Kumar S, Huang J, Abbassi-Ghadi N, Mackenzie HA, Veselkov KA, Hoare JM, Lovat LB, Spanel P, Smith D, Hanna GB. Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma. Ann Surg. 2015;262(6):981-90.
  23. Hicks LC, Huang J, Kumar S, Powles ST, Orchard TR, Hanna GB, Williams HR. Analysis of Exhaled Breath Volatile Organic Compounds in Inflammatory Bowel Disease: A Pilot Study. J Crohns Colitis. 2015;9(9):731-7.
  24. Boshier PR, Mistry V, Cushnir JR, Kon OM, Elkin SL, Curtis S, Marczin N, Hanna GB. Breath metabolite response to major upper gastrointestinal surgery. J Surg Res. 2015;193(2):704-12.
  25. Huang J, Kumar S, Hanna GB. Investigation of C3-C10 aldehydes in the exhaled breath of healthy subjects using selected ion flow tube-mass spectrometry (SIFT-MS). J Breath Res. 2014;8(3):037104.
  26. Kumar S, Huang J, Abbassi-Ghadi N, Spanel P, Smith D, Hanna GB. Selected ion flow tube mass spectrometry analysis of exhaled breath for volatile organic compound profiling of esophago-gastric cancer. Anal Chem. 2013;85(12):6121-8.
  27. Huang J, Kumar S, Abbassi-Ghadi N, Spanel P, Smith D, Hanna GB. Selected ion flow tube mass spectrometry analysis of volatile metabolites in urine headspace for the profiling of gastro-esophageal cancer. Anal Chem. 2013;85(6):3409-16.
  28. Boshier PR, Hanna GB, Marczin N. Exhaled nitric oxide as biomarker of acute lung injury: an unfulfilled promise? J Breath Res. 2013;7(1):017118.
  29. Kumar S, Huang J, Cushnir JR, Spanel P, Smith D, Hanna GB. Selected ion flow tube-MS analysis of headspace vapor from gastric content for the diagnosis of gastro-esophageal cancer. Anal Chem. 2012;84(21):9550-7.
  30. Boshier PR, Priest OH, Hanna GB, Marczin N. Influence of respiratory variables on the on-line detection of exhaled trace gases by PTR-MS. Thorax. 2011;66(10):919-20.
  31. Boshier PR, Cushnir JR, Mistry V, Knaggs A, Spanel P, Smith D, Hanna GB. On-line, real time monitoring of exhaled trace gases by SIFT-MS in the perioperative setting: a feasibility study. Analyst. 2011;136(16):3233-7.
  32. Boshier PR, Marczin N, Hanna GB. Repeatability of the measurement of exhaled volatile metabolites using selected ion flow tube mass spectrometry. J Am Soc Mass Spectrom. 2010;21(6):1070-4.
  33. Boshier PR, Cushnir JR, Priest OH, Marczin N, Hanna GB. Variation in the levels of volatile trace gases within three hospital environments: implications for clinical breath testing. J Breath Res. 2010;4(3):031001.

Our researchers

Professor Patrik Spanel

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Professor Patrik Spanel
Professor of Chemical Physics

Mr Stefan Antonowicz

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Mr Stefan Antonowicz
Post Doctoral Researcher

Mr Stefan Antonowicz

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Mr Stefan Antonowicz
Post Doctoral Researcher