Dr Shishir Shetty FRCP PhD

Shishir Shetty

Institute of Immunology and Immunotherapy
Reader in Liver Tumour Immunology
Cancer Research UK Advanced Clinician Scientist
Honorary Consultant Hepatologist

Contact details

Address
Centre for Liver and Gastrointestinal Research
Institute of Immunology and Immunotherapy
Medical School
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

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 is UK Chief Investigator.

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

Dr 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

Postgraduate supervision

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

  • Lymphocyte adhesion and migration via hepatic endothelium.
  • Lymphocyte subset recruitment to the inflamed liver.
  • The role of C-type lectins in chronic liver disease and primary liver cancer.

If you are interested in studying any of these subject areas please contact Dr Shetty on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

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

We study 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

MRC project grant 2018-2021

In collaboration with Dr Matt Hoare Cambridge Cancer Centre we are studying the mechanisms of senescence driven immune cell recruitment across liver endothelial cells.

HUNTER CRUK Accelerator 2019-2024

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

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.

Wellcome MIDAS project

The role of atypical adhesion molecules on liver endothelium expressed on hepatic endothelium in regulating the immune microenvironment during liver injury.

Other activities

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

Publications

Recent publications

Article

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

Patten, D & Shetty, S 2019, 'The role of stabilin-1 in lymphocyte trafficking and macrophage scavenging in the liver microenvironment', Biomolecules, vol. 9, no. 7, 283. https://doi.org/10.3390/biom9070283

Patten, DA, Shepherd, EL, Weston, CJ & Shetty, S 2019, 'Novel targets in the immune microenvironment of the hepatic sinusoids for treating liver diseases', Seminars in Liver Disease, vol. 39, no. 2, pp. 111-123. https://doi.org/10.1055/s-0039-1678727

Patten, DA, Kamarajah, SK, Rose, JM, Tickle, J, Shepherd, EL, Adams, DH, Weston, CJ & Shetty, S 2017, 'SCARF-1 promotes adhesion of CD4+ T cells to human hepatic sinusoidal endothelium under conditions of shear stress', Scientific Reports, vol. 7, 17600. https://doi.org/10.1038/s41598-017-17928-4

Wadkin, JCR, Patten, DA, Kamarajah, S, Shepherd, EL, Novitskaia, V, Berditchevski, F, Adams, DH, Weston, CJ & Shetty, S 2017, 'CD151 supports VCAM-1 mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver diseases and hepatocellular carcinoma', American journal of physiology. Gastrointestinal and liver physiology, vol. 313, no. 2, pp. G138-G149. https://doi.org/10.1152/ajpgi.00411.2016

Atkin, C, Earwaker, P, Pallan, A, Shetty, S, Punia, P & Ma, Y 2017, 'Exceptional serological and radiological response to sorafenib in 2 patients with advanced hepatocellular carcinoma and chronic hepatitis C viral infection: case report and review of the literature', BMC Gastroenterology, vol. 17, 30. https://doi.org/10.1186/s12876-017-0585-x

Than, NN, Ghazanfar, A, Hodson, J, Tehami, N, Coldham, C, Mergental, H, Manas, D, Shah, T, Newsome, P, Reeves, H & Shetty, S 2017, 'Comparing clinical presentations, treatments and outcomes in hepatocellular carcinoma due to Hepatitis C and Non Alcoholic Fatty Liver Disease', QJM: An International Journal of Medicine, vol. 110, no. 2, pp. 73-81. https://doi.org/10.1093/qjmed/hcw151

Patten, D, Wilson, G, Bailey, D, Shaw, R, Jalkanen, S, Salmi, M, Rot, A, Weston, C, Adams, D & Shetty, S 2016, 'Human liver sinusoidal endothelial cells promote intracellular crawling of lymphocytes during recruitment - a new step in migration', Hepatology. https://doi.org/10.1002/hep.28879

Hoare, M, Ito, Y, Kang, T-W, Weekes, MP, Matheson, NJ, Patten, D, Shetty, S, Parry, AJ, Menon, S, Salama, R, Antrobus, R, Tomimatsu, K, Howat, W, Lehner, PJ, Zender, L & Narita, M 2016, 'NOTCH1 mediates a switch between two distinct secretomes during senescence', Nature Cell Biology, vol. 18, no. 9, pp. 979-92. https://doi.org/10.1038/ncb3397

Rantakari, P, Patten, D, Valtonen, J, Karikoski, M, Gerke, H, Dawes, H, Laurila, J, Ohlmeier, S, Elima, K, Hubscher, S, Weston, C, Jalkanen, S, Adams, D, Salmi, M & Shetty, S 2016, 'Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury', National Academy of Sciences. Proceedings, vol. 113, no. 33, pp. 9298–9303. https://doi.org/10.1073/pnas.1604780113, https://doi.org/10.1073/pnas.1604780113

Comment/debate

Shetty, S 2018, 'Chronic liver disease: scavenger hunt for novel therapies.', The Lancet.

Editorial

O'Rourke, J, Patten, D & Shetty, S 2019, 'Tumour-associated macrophages in hepatocellular carcinoma: pressing the metabolic switch to prevent T cell responses', Journal of Hepatology, vol. 71, no. 2, pp. 243-245. https://doi.org/10.1016/j.jhep.2019.05.019

Shetty, S 2019, 'Bile acid metabolism and T cell responses in cholangiopathy: Not one-way traffic.', Journal of Hepatology, vol. 71, no. 4, pp. 657-659. https://doi.org/10.1016/j.jhep.2019.07.012

Review article

Patten, DA & Shetty, S 2018, 'More Than Just a Removal Service: Scavenger Receptors in Leukocyte Trafficking', Frontiers in immunology, vol. 9, 2904. https://doi.org/10.3389/fimmu.2018.02904

Shetty, S, Lalor, PF & Adams, DH 2018, 'Liver sinusoidal endothelial cells - gatekeepers of hepatic immunity', Nature Reviews. Gastroenterology & Hepatology. https://doi.org/10.1038/s41575-018-0020-y

View all publications in research portal