Professor Shishir Shetty FRCP PhD

Professor Shishir Shetty

Department of Immunology and Immunotherapy
Professor in Liver Tumour Immunology, Interim Director of the Centre for Liver and Gastrointestinal Research
Cancer Research UK Advanced Clinician Scientist
Honorary Consultant Hepatologist

Contact details

Telephone
+44 (0)121 415 8700
Email
s.shetty@bham.ac.uk
View my research portal
Address
Centre for Liver and Gastrointestinal Research
Department of Immunology and Immunotherapy
Birmingham Medical School
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK
Understanding liver disease and liver cancer through art

Shishir Shetty is a Cancer Research UK Advanced Clinician Scientist and principal investigator in the Centre for Liver and Gastrointestinal Research. He is also a consultant hepatologist at the Queen Elizabeth Hospital where he specialises in the management of hepatocellular cancer and neuroendocrine tumour.

His basic science research aims to study the factors which promote cancer growth in the setting of chronic inflammation with a focus on immune cell/endothelial interactions. His translational work includes the MATINS trial, an early phase clinical trial of a novel immunotherapy in the setting of advanced cancer for which he was UK Chief Investigator.

Professor Shetty is currently liver theme co-lead within the NIHR Birmingham Biomedical Research Centre and Interim Director of the Centre for Liver and Gastrointestinal Research.

ORCID iD: 0000-002-4729-2173

Qualifications

  • Fellowship of the Royal College of Physicians, 2017
  • PhD Immunology, University of Birmingham 2011
  • Membership of the Royal College of Physicians, 2002
  • MbChB, Leicester 1999

Biography

Scavenger receptors - a future target for liver fibrosis | Dr Shishir Shetty

Professor Shishir Shetty graduated in Medicine from the University of Leicester in 1999. He underwent general medical training in Liverpool followed by specialisation in Gastroenterology and Hepatology at the Royal Free in London and then the West Midlands Deanery. In 2007 he obtained a BRET-CORE fellowship to undertake a PhD in the laboratory of Professor David Adams in Birmingham. During his PhD he discovered that the scavenger receptor CLEVER-1/stabilin-1 was a hepatic adhesion molecule for regulatory T cells.

In recognition of this work he was awarded the Dame Sheila Sherlock research medal from the British Association for the Study of the Liver in 2013 and the CORE charity research prize. On completing his specialist medical training he was awarded a Wellcome Trust Intermediate Fellowship in 2012 and appointed as Honorary Consultant Hepatologist at the Queen Elizabeth Liver transplant unit in Birmingham. The work during his intermediate fellowship led to the discovery that CLEVER-1/stabilin-1 plays a critical role in liver fibrosis and remodelling.

In recognition of this work he was awarded the United European Gastroenterology Rising Star Award and the Lancet Young Investigator Award in 2017. In 2019, Shishir was awarded an Advanced Clinician Scientist Fellowship from CRUK to study the role of scavenger receptors in hepatocellular cancer.

Teaching

  • Member of the Clinical Academic Training Operations Group and Academic lead for Gastroenterology and Hepatology
  • Lectures on BMedSci Course

Postgraduate supervision

Professor Shetty is interested in supervising doctoral research students in the following areas:

  • Imaging and analysis of immune cell adhesion and migration via liver endothelial cells
  • Leukocyte/endothelial interactions in the inflamed liver and liver cancer
  • The role of C-type lectins and scavenger receptors in liver fibrosis and liver cancer

If you are interesting in studying any of these subject areas please contact Professor Shishir Shetty directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Dr Shishir Shetty on CLEVER-1

Research interests

Professor Shetty studies the development of cancer in the setting of chronic inflammation with a focus on hepatocellular cancer (HCC). There is now strong evidence that for cancer to develop and grow it has to evade the immune system and promote a tissue microenvironment that prevents immune eradication. HCC develops on the background chronic liver disease in the vast majority of patients. HCC therefore grows in a complex multicellular environment which involves inflammation, fibrosis and epithelial transformation. The clinical challenge is to find new immunotherapies for HCC which can eradicate the tumour but do not exacerbate the underlying liver inflammation. Our previous work on the molecule stabilin-1/CLEVER-1 highlights that scavenger receptors play distinct homeostatic roles in the setting of tissue injury and therefore may be attractive targets for cancer immunotherapy. Scavenger receptors are highly expressed by endothelial cells and macrophages and this has led us to study the contribution of these cell types to the tumour microenvironment.

Current projects

CRUK Advanced Clinical Scientist Fellowship 2020-2025

This fellowship aims to understand how scavenger receptors regulate the tumour microenvironment and their potential as novel immunotherapies.

HUNTER CRUK Accelerator 2019-2024

Professor Shetty is part of the HUNTER collaboration, made up of groups from the UK, Spain and Italy to advance the knowledge of the immune microenvironment of HCC. Their focus in Birmingham is on characterising tumour endothelial cells and their contribution to immune cell recruitment.

Current studentships

lifeTIME CDT PhD studentship 2021-2025 – Developing models to test immunotherapies for liver disease and liver cancer.

lifeTIME CDT PhD studentship 2023-2027 - Tracking of cargo loaded macrophages across tumour endothelium in the context of liver cancer.

CRUK Clinical Fellowship 2021-2024 - The role of CD73 in hepatocellular cancer.

Other activities

  • Member of the Steering Committee for the MATINS Global multicentre Phase I/II trial.

Publications

Recent publications

Article

Kennedy, JI, Davies, SP, Hewett, PW, Wilkinson, AL, Oo, YH, Lu, W-Y, El Haj, AJ & Shetty, S 2024, 'Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells: the potential for testing immunotherapies and cell therapy trafficking', Frontiers in cell and developmental biology, vol. 12, 1359451. https://doi.org/10.3389/fcell.2024.1359451

Wilkinson, AL, Bannister, ME, O'Keeffe, A, Weston, CJ, Lalor, PF, Shetty, S & Patten, DA 2024, 'Protocol to study monocyte transmigration across primary human liver endothelial cells under physiological shear flow conditions in vitro', STAR Protocols, vol. 5, no. 4, 103431. https://doi.org/10.1016/j.xpro.2024.103431

Rannikko, JH, Verlingue, L, De miguel, M, Pasanen, A, Robbrecht, D, Skytta, T, Iivanainen, S, Shetty, S, Ma, YT, Graham, DM, Arora, SP, Jaakkola, P, Yap, C, Xiang, Y, Mandelin, J, Karvonen, MK, Jalkanen, J, Karaman, S, Koivunen, JP, Minchom, A, Hollmén, M & Bono, P 2023, 'Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial', Cell Reports Medicine, vol. 4, no. 12, 101307. https://doi.org/10.1016/j.xcrm.2023.101307

Faulkes, RE, Rehman, Z, Palanichamy, S, Zakeri, N, Coldham, C, Dasari, BVM, Perera, MTPR, Rajoriya, N, Shetty, S & Shah, T 2023, 'Comparable Overall Survival in Patients with Hepatocellular Carcinoma Diagnosed within and outside a Surveillance Programme: The Potential Impact of Liver Cirrhosis', Cancers, vol. 15, no. 3, 978. https://doi.org/10.3390/cancers15030978

De Souza, S, Kahol de Jong, J, Perone, Y, Shetty, S, Qurashi, M, Vithayathil, M, Shah, T, Ross, P, Temperley, L, Yip, VS, Banerjee, A, Bettinger, D, Sturm, L, Reeves, HL, Geh, D, Orr, J, Allen, B, Jones, RP & Sharma, R 2023, 'Impact of COVID-19 on 1-Year Survival Outcomes in Hepatocellular Carcinoma: A Multicenter Cohort Study', Cancers, vol. 15, no. 13, 3378. https://doi.org/10.3390/cancers15133378

Wilkinson, AL, Hulme, S, Kennedy, JI, Mann, ER, Horn, P, Shepherd, EL, Yin, K, Zaki, MYW, Hardisty, G, Lu, W-Y, Rantakari, P, Adams, DH, Salmi, M, Hoare, M, Patten, DA & Shetty, S 2023, 'The senescent secretome drives PLVAP expression in cultured human hepatic endothelia to promote monocyte transmigration', iScience, vol. 26, no. 10, 107966. https://doi.org/10.1016/j.isci.2023.107966

Shah, HA, Faulkes, R, Coldham, C, Shetty, S & Shah, T 2022, 'Effects of transplantation-related immunosuppression on co-existent neuroendocrine tumours', QJM: An International Journal of Medicine, vol. 115, no. 10, pp. 661-664. https://doi.org/10.1093/qjmed/hcac036

Zaki, MYW, Fathi, AM, Samir, S, Eldafashi, N, William, KY, Nazmy, MH, Fathy, M, Gill, US & Shetty, S 2022, 'Innate and Adaptive Immunopathogeneses in Viral Hepatitis; Crucial Determinants of Hepatocellular Carcinoma', Cancers, vol. 14, no. 5, 1255. https://doi.org/10.3390/cancers14051255

Yin, K, Patten, D, Gough, S, de Barros Gonçalves, S, Chan, A, Olan, I, Cassidy, L, Poblocka, M, Zhu, H, Lun, A, Schuijs, M, Young, A, Martinez-Jimenez, C, Halim, TYF, Shetty, S, Narita, M & Hoare, M 2022, 'Senescence-induced endothelial phenotypes underpin immune-mediated senescence surveillance', Genes & Development, vol. 36, no. 9-10, pp. 533-549. https://doi.org/10.1101/gad.349585.122

Zaki, MYW, Shetty, S, Wilkinson, AL, Patten, DA, Oakley, F & Reeves, H 2021, 'A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma', Journal of Visualized Experiments , no. 175, e62868. https://doi.org/10.3791/62868

Patten, DA, Wilkinson, AL, O'Keeffe, A & Shetty, S 2021, 'Scavenger Receptors: Novel Roles in the Pathogenesis of Liver Inflammation and Cancer', Seminars in Liver Disease, vol. 42, no. 1, pp. 61-76. https://doi.org/10.1055/s-0041-1733876

Virtakoivu, R, Rannikko, JH, Viitala, M, Vaura, F, Takeda, A, Lönnberg, T, Koivunen, J, Jaakkola, P, Pasanen, A, Shetty, S, Jonge, MJAD, Robbrecht, D, Ma, YT, Skyttä, T, Minchom, A, Jalkanen, S, Karvonen, MK, Mandelin, J, Bono, P & Hollmen, M 2021, 'Systemic blockade of Clever-1 elicits lymphocyte activation alongside checkpoint molecule downregulation in patients with solid tumors: results from a phase I/II clinical trial', Clinical Cancer Research, vol. 27, no. 15, pp. 4205-4220. https://doi.org/10.1158/1078-0432.CCR-20-4862

Sagar, VM, Herring, K, Curbishley, S, Hodson, J, Fletcher, P, Karkhanis, S, Mehrzad, H, Punia, P, Shah, T, Shetty, S & Ma, YT 2021, 'The potential of PIVKA-II as a treatment response biomarker in hepatocellular carcinoma: a prospective United Kingdom cohort study', OncoTarget, vol. 12, no. 24, pp. 2338-2350. https://doi.org/10.18632/oncotarget.28136

Shetty, S 2020, 'Hepatocellular carcinoma demonstrates heterogeneous growth patterns in a multi-center cohort of patients with cirrhosis.', Hepatology.

Editorial

Shetty, S, Lujambio, A & Tacke, F 2021, 'Editorial: overcoming the immune microenvironment of hepatocellular cancer', Frontiers in immunology, vol. 12, 707329. https://doi.org/10.3389/fimmu.2021.707329

View all publications in research portal