... understanding life in molecular detail

Dr Stephen Griffin

Antivirals, viroporins, liver cancer, hepatitis c virus


Our goal is the development of combined antiviral and anti-tumour therapies for virus-associated malignancies. Key interests centre on how hepatitis C virus (HCV) infection leads to liver cancer and antiviral development targeting virus-coded ion channels.

Current major projects include:
  • Viral Oncology: HCV infection and Liver Cancer
  • Antiviral Development: Targeting Virus Ion Channels
  • Molecular Virology: assembly and secretion of infectious HCV particles

Our work spans the translational pipeline, from atomic structures and rational drug design, through molecular virology and up to ex vivo human tissue models and translational clinical studies.

Viral Oncology:

We are investigating how HCV infection may directly cause hepatocellular carcinoma (HCC) working closely with Heiko Wurdak (LICSP), using a single cell approach incorporating primary liver-resident progenitor cells.

 

We are also assessing “oncolytic” Reovirus for anti-HCC activity in combination with targeted therapies such as Sorafenib. This involves close collaboration with Alan Melcher and Graham Cook (LICSP) as well as ongoing patient studies with Dr Daniel Swinson (SJUH).

Antiviral Development:

Many viruses encode essential ion channel proteins, termed “viroporins”. Discovering the function of the HCV viroporin, p7, led us to pursue antiviral programmes targeting this and other channels. Our p7 NMR structure, solved with the Astbury NMR Facility, permits rational drug development working with Richard Foster (Chemistry). We also run a p7 related clinical trial, “HepRiACT”, with St James’ Hospital Hepatology.

Interests extend to other viroporins, including the M2 channel of pandemic influenza (with Richard Foster, Prof Wendy Barclay (Imperial College, London) and David Fedida (UBC, Vancouver). A closely collaborative MRC-funded project led by Andrew Macdonald, also with Richard Foster, focuses on the E5 protein of papillomavirus, a unique Viroporin that acts as an oncogene in the development of Cervical Cancer.

Molecular Virology:

We have a major interest in how p7 mediates assembly and secretion of infectious HCV particles, a relatively unknown aspect of HCV virology, in close collaboration with Prof Mark Harris, Prof David Rowlands and Dr Jamel Mankouri.

Detailed research programme                  Close ▲
SG.jpg

Associate Professor
MA (Cambridge) PhD (Cambridge)
UK Society of General Microbiology, Sir Howard Dalton Prize (2003)

Post-Doctoral Fellow, Faculty of Biological Sciences, University of Le
MRC New Investigator Independent Fellow, Faculty of Biological Science

Wellcome Trust Brenner Buildin
School of Molecular and Cellular Biology
0113 3438637
s.d.c.griffin@leeds.ac.uk

Selected Publications

  1. Mankouri J, Walter C, Stewart H, Bentham M, Park WS, Heo WD, Fukuda M, Griffin S*, Harris M*. Release of infectious hepatitis C virus from Huh7 cells occurs via a trans-Golgi network to endosome pathway independent of VLDL. J Virol. 2016 May 25. pii: JVI.00826-16

    *Joint corresponding author

  2. Walter S, Bollenbach A, Doerrbecker J, Pfaender S, Brown RJ, Vieyres G, Scott C, Foster R, Kumar A, Zitzmann N, Griffin S, Penin F, Pietschmann T, Steinmann E. Ion Channel Function and Cross-Species Determinants in Viral Assembly of Nonprimate Hepacivirus p7. J Virol. 2016 Apr 29;90(10):5075-89. doi: 10.1128/JVI.00132-16
     

  3. Jebar AH, Errington-Mais F, Vile RG, Selby PJ, Melcher AA, Griffin S. Progress in clinical oncolytic virus-based therapy for hepatocellular carcinoma. J Gen Virol. 2015 Jul;96(Pt 7):1533-50. doi: 10.1099/vir.0.000098.

     

  4. Foster TL, Thompson GS, Kalverda AP, Kankanala J, Bentham M, Wetherill LF, Thompson J, Barker AM, Clarke D, Noerenberg M, Pearson AR, Rowlands DJ, Homans SW, Harris M, Foster R, Griffin S. Structure-guided design affirms inhibitors of hepatitis C virus p7 as a viable class of antivirals targeting virion release. Hepatology. 2014 Feb;59(2):408-22. doi: 10.1002/hep.26685