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Research output

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ResearchGate Profile

See my ResearchGate profile for the most up to date list of my research outputs

Preprints

Mapping vascular plasticity in liver fibrogenesis identifies novel fibrosis-associated endothelial cells in early-stage liver disease 

Christina Gkantsinikoudi, Joshua P Dignam, Raju Kumar, Elliot Jokl, Wenhao Li, Maryna Samus, Stephanie Landi, Varinder S Athwal, Timothy J Kendall, Antal Rot, Jonathan A Fallowfield, Karen Piper Hanley, William Alazawi, Neil P Dufton

bioRxiv 2026 doi:  10.64898/2026.03.12.710459


Spartan: activation-aware framework for spatial domain and variable gene discovery

Mohammad Faiz Iqbal Faiz, Elliot Jokl, Rachel Jennings, Karen Piper Hanley, Andrew Sharrocks, Mudassar Iqbal, Syed Murtuza Baker

bioRxiv 2026 doi:10.64898/2026.02.18.706570

  

SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis

Laurence Pearmain, Elliot Jokl, Kara Simpson, Lindsay Birchall, Yaqing Ou, Craig Lawless, Angela Simpson, Lizzie Mann, Nick Scott, Rajesh Shah, Rajamiyer Venkateswaran, Stefan Stanel, Conal Hayton, Pilar Rivera-Ortega, Phil Hansbro, Neil A Hanley, John F Blaikley, Karen Piper Hanley

bioRxiv 2024 doi:10.1101/2024.01.21.576509 


This study showed that the inability to express SOX9 has stage-dependent impacts on lung disease progression, identifying severity associated markers in acute injury and fibrotic stages of bleomycin induced injury altered in response to SOX9 loss. Several of these show a predictive ability for poor outcomes in the time course of COVID-19 infection and pulmonary fibrosis in human patients.


Papers

SOX9 plays an essential role in myofibroblast driven hepatic granuloma integrity and parenchymal repair during schistosomiasis-induced liver damage   


Kim Su*, Elliot Jokl*, Alice Costain*, Kara Simpson, Antonn Cheeseman, Alexander Phythian-Adams, Kevin N. Couper, Andrew S. MacDonald, Karen Piper Hanley *joint first authors

PLOS Pathogens 21(6): e1012928 (2025) doi:10.1371/journal.ppat.1012928 


Here we demonstrated that the inability to express the Sox9 gene led to a more disorganised granuloma in response to Schistosomiasis infection in the liver. Though extracellular matrix deposition was less intense around eggs, these "leaky" granulomas led to more diffuse fibrotic damage throughout the tissue.


Spatial gene regulatory networks driving cell state transitions during human liver disease


Nigel L Hammond, Syed Murtuza Baker, Sokratia Georgaka, Ali Al-Anbaki, Elliot Jokl, Kara Simpson, Rosa Sanchez-Alvarez, Varinder S Athwal, Huw Purssell, Ajith K Siriwardena, Harry V M Spiers, Mike J Dixon, Leoma D Bere, Adam P Jones, Michael J Haley, Kevin N Couper, Nicoletta Bobola, Andrew D Sharrocks, Neil A Hanley, Magnus Rattray & Karen Piper Hanley

EMBO Mol Med 17, 1452–1474 (2025) doi:10.1038/s44321-025-00230-6 


In this study we generated spatial transcriptomic and single nuclear RNA and ATAC seq data of fibrotic livers to develop a profile of diseased hepatocyte states forming in response to the scar microenvironment, developing an understanding of the gene regulatory networks underpinning a transition into disease.


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, Sayyid Raza, 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

Cell Reports Nov 2023 doi: 10.1016/j.celrep.2023.113414


This paper explored how the nuclei and chromatin organsiation of hepatic stellate cells, the main mediators of excessive extracellular matrix deposition in fibrotic liver disease, changes as they activate in stiffer environments. We showed that the mechanical forces influence hepatic stellate cell gene expression and that the loss of PAK1 interferes with this process, highlighting this as a potential therapeutic target to limit fibrosis. 


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

Multiomic analyses demonstrate hepatocyte SOX9 loss exacerbates fibrosis and HCC development in the DEN-CCl4 mouse model

Oral presentation; 2nd International Conference of Liver Pathobiology: From Bench to Bedside 2025, Crete (Travel Award Recipient)

Elliot Jokl, Syed Murtuza Baker, Sokratia Georgaka, Kara Simpson, Rosa Sanchez-Alvarez, Nigel Hammond, Chris Mysko, Varinder Athwal, Richard Hubner, Karen Piper Hanley


Multiomic analyses demonstrate hepatocyte SOX9 loss exacerbates fibrosis and HCC development in the DEN-CCl4 mouse model 

Oral presentation; HCC UK 2025, Manchester, UK

Elliot Jokl, Syed Murtuza Baker, Sokratia Georgaka, Kara Simpson, Rosa Sanchez-Alvarez, Nigel Hammond, Chris Mysko, Varinder Athwal, Richard Hubner, Karen Piper Hanley


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

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