Research output

Preprints

A spatial map of human liver cirrhosis reveals the patho-architecture and gene signatures associated with cell state transitions during liver disease

Nigel L Hammond, Syed Murtuza Baker, Sokratia Georgaka, Ali Al-Anbaki, Elliot Jokl, Kara Simpson, Varinder S Athwal, Ajith K Siriwardena, Harry VM Spiers, Mike J Dixon, Nicoletta Bobola, Andrew D Sharrocks, Neil A Hanley, Magnus Rattray, Karen Piper Hanley

doi: 10.1101/2023.06.28.546905

PAK1-dependant mechanotransduction enables myofibroblast nuclear adaptation and chromatin organisation during fibrosis

Elliot Jokl*, Aoibheann F Mullan*, Kara Simpson, Lindsay Birchall, Laurence Pearmain, Katherine Martin, James Pritchett, Rajesh Shah, Nigel W Hodson, Craig J Williams, Elizabeth Camacho, Leo Zeef, Ian Donaldson, Varinder S Athwal, Neil A Hanley, Karen Piper Hanley *joint first authors

doi: 10.1101/2023.03.31.535067

Papers

Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease

Elliot Jokl*, Jessica Llewellyn*, Kara Simpson, Oluwatobi Adegboye, James Pritchett, Leo Zeef, Ian Donaldson, Varinder S. Athwal, Huw Purssell, Oliver Street, Lucy Bennett, Indra Neil Guha, Neil A. Hanley, Qing-Jun Meng, Karen Piper Hanley on behalf of the ID LIVER consortium *joint first authors

Cells 12, no. 12: 1582. doi: 10.3390/cells12121582

This work examined the impact of circadian rhythm disruption on the activation of hepatic stellate cells, showing that this leads to a primed state that worsens fibrotic injury in mice. We leveraged the genes that had altered expression in this primed state as potential biomarkers, using the ID LIVER cohort to show elevated levels of AOC3 in patients with evidence of fibrosis or high risk of liver disease.

SOX9 is required for kidney fibrosis and regulates NAV3 to control renal myofibroblast function in mice and humans

Sayyid Raza*, Elliot Jokl*, James Pritchett, Katherine Martin, Kim Su, Kara Simpson, Aoibheann F Mullan, Varinder Athwal, Daniel T Doherty, Leo Zeef, Neil C Henderson, Philip A Kalra, Neil A Hanley, Karen Piper Hanley * Joint first authors

Sci Signal . 2021 Mar 2;14(672):eabb4282. doi: 10.1126/scisignal.abb4282.

This study explored the role of SOX9 in kidney fibrosis using the unilateral ureteral obstruction model with or without repression of SOX9 expression, demonstrating that markers of fibrosis are significantly reduced in the absence of SOX9. RNAseq and relative gene expression analyses identified Neural Navigator 3 (NAV3) as a novel, SOX9-dependent marker of fibrosis. Inhibiting Nav3 in cultured kidney pericytes and HEK fibroblasts impaired migration, cytoskeletal stability and mechanotransduction.

Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications

Katherine Martin , Anas Hatab, Varinder S Athwal, Elliot Jokl, Karen Piper Hanley

Curr Diab Rep . 2021 Feb 5;21(3):8. doi: 10.1007/s11892-021-01377-5.

Transcriptional upregulation of Bag3, a chaperone-assisted selective autophagy factor, in animal models of KY-deficient hereditary myopathy

Elliot J. Jokl, Gideon L. Hughes, Tobias Cracknell, Mary E. Pownall, Gonzalo Blanco

Disease Models & Mechanisms 2018 11: dmm033225 doi: 10.1242/dmm.033225 Published 6 July 2018

In this paper, based on my PhD project, we showed that the absence of the cytoskeletal protein KY results in the apparent upregulation of the chaperone BAG3. In this project I generated in vitro myoblast and in vivo zebrafish models of KY deficiency using CRISPR/Cas9 and explored common hallmarks with the established ky/ky mouse model. My work suggests that the absence of KY leads to a baseline of elevated cell stress and a failure to further upregulate this in response to mechanical stimulation.

Disrupted autophagy undermines skeletal muscle adaptation and integrity

Elliot J. Jokl and Gonzalo Blanco

Mamm Genome. 2016; doi: 10.1007/s00335-016-9659-2 Published online 2 Aug 2016

This review explored the critical role of autophagy in skeletal muscle and the myopathies resulting from mutations or disruption to autophagy components.

Presented Conference Abstracts

CLOCKΔ19 circadian disruption primes myofibroblasts for accelerated activation and fibrotic progression

Oral presentation; EASL ILC 2023, Vienna, Austria

Elliot Jokl, Jessica Llewelyn, Kara Simpson, Oluwatobi Adegboye, James Pritchett, Leo Zeef, Qing-Jun Meng, Karen Piper Hanley

SOX9 is required for fibrosis in multiple organs and regulates NAV3 to control myofibroblast function

Poster presentation; Keystone Symposia: Fibrosis and Tissue Repair 2020, Victoria, Canada

Elliot J Jokl, Sayyid Raza, James Pritchett, Katherine Martin, Kim Su, Kara Simpson, Aoibheann F Mullan, Varinder S Athwal, Daniel T Doherty, Leo Zeef, Neil Henderson, Philip A Kalra, Neil A Hanley, Karen Piper Hanley

Mechanotransduction at the z-disc of skeletal muscle

Oral and poster presentation; White Rose Mechanistic Biology DTP Annual Research Symposium 2016

Elliot Jokl, Mary E Pownall, Gonzalo Blanco

No recycling = no growth? Insights from the ky/ky mouse

Poster presentation; 44th European Muscle Conference 2015, Warsaw, Poland

Elliot Jokl, Mary E Pownall, Gonzalo Blanco

Mechanotransduction at the z-disc of skeletal muscle

Poster presentation; London Myology Forum December 2013, London, UK

Elliot Jokl, Mary E Pownall, Gonzalo Blanco