Neil Henderson Group (Affiliate)

Organ fibrosis (scarring) is a major cause of morbidity and mortality worldwide, and as yet there are no effective anti-fibrotic treatments. My lab is interested in the cellular and molecular mechanisms that drive organ fibrosis, and also the molecular pathways which are responsible for efficient wound healing and healthy tissue regeneration following injury. By understanding more about how organs scar, heal and regenerate we hope to develop new treatments for patients with organ fibrosis.

Single-cell genomics approaches are transforming our understanding of disease pathogenesis, allowing interrogation of homeostatic and pathogenic cell populations at unprecedented resolution, and adding an illuminating dimension to transcriptomic information relative to traditional methods that profile bulk cell populations. The single cell genomics field has developed rapidly over the last few years, chiefly because these approaches allow powerful, unbiased exploration of cell states and types at single-cell resolution, resulting in unexpected novel insights into tissue biology and disease mechanisms.  

The convergence of these multi-modal single-cell technologies represent a remarkable opportunity to decode the molecular mechanisms regulating human tissue fibrosis and regeneration at single cell resolution, which we hope will inform and accelerate the development of effective new therapies for patients with fibrotic diseases.

Contact

Neil.Henderson@ed.ac.uk

Selected Publications

Fibrosis: from mechanisms to medicines. Henderson NC, Rieder F, Wynn TA. Nature. 2020 Nov;587(7835):555-566. doi: 10.1038/s41586-020-2938-9. 

Decoding myofibroblast origins in human kidney fibrosis.Kuppe C, Ibrahim MM, Kranz J, Zhang X, Ziegler S, Perales-Patón J, Jansen J, Reimer KC, Smith JR, Dobie R, Wilson-Kanamori JR, Halder M, Xu Y, Kabgani N, Kaesler N, Klaus M, Gernhold L, Puelles VG, Huber TB, Boor P, Menzel S, Hoogenboezem RM, Bindels EMJ, Steffens J, Floege J, Schneider RK, Saez-Rodriguez J, Henderson NC*, Kramann R*. Nature. 2020 Nov 11. doi: 10.1038/s41586-020-2941-1. *joint senior authors.

Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis. Ramachandran P, Matchett KP, Dobie R, Wilson-Kanamori JR, Henderson NC.  Nat Rev Gastroenterol Hepatol 2020, Jun 1. doi: 10.1038/s41575-020-0304-x

Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Ramachandran P, Dobie R, Wilson-Kanamori JR,  Dora EF, Henderson BEP, Luu NT, Portman JR, Matchett KP, Brice M, Marwick JA, Taylor RS, Efremova M, Vento-Tormo R, Carragher NO, Kendall TJ, Fallowfield JA, Harrison EM, Mole DJ, Wigmore SJ, Newsome PN, C. JWeston J, Iredale JP, Tacke F, Pollard JW, Ponting CP, Marioni JC, Teichmann SA, Henderson NC.  Nature 2019, Nov 21. doi: 10.1038/s41586-019-1631-3

Single-cell transcriptomics uncovers zonation of function in the mesenchyme during liver fibrosis. Dobie R, Wilson-Kanamori JR, Henderson BE, Smith JR, Matchett KP, Portman JR, Wallenborg K, Picelli S, Zagorska A, Pendem SV, Hudson TE, Wu MM, Budas GR, Breckenridge DG, Harrison EM, Mole DJ, Wigmore SJ, Ramachandran P, Ponting CP, Teichmann SA, Marioni JC, Henderson NC.  Cell Reports 2019, Nov 12. doi: 10.1016/j.celrep.2019.10.024

αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.  Murray IR, Gonzalez ZN, Baily J, Dobie R, Wallace RJ, Mackinnon AC, Smith JR, Greenhalgh SN, Thompson AI, Conroy KP, Griggs DW, Ruminski PG, Gray GA, Singh M, Campbell MA, Kendall TJ, Dai J, Li Y, Iredale JP, Simpson H, Huard J, Péault B, Henderson NC.  Nature Communications 2017, Oct 24.  doi: 10.1038/s41467-017-01097-z  

Targeting of α_v integrin identifies a core molecular pathway that regulates fibrosis in several organs.  Henderson NC, Arnold TD, Katamura Y, Giacomini MM, J Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG, Griggs DW, Prinsen MJ, Maher JJ, Iredale JP, Lacy-Hulbert A, Adams RH, Sheppard D.  Nature Medicine 2013, Dec. doi: 10.1038/nm.3282

• Chris Ponting, MRC Human Genetics Unit, University of Edinburgh  
• John Marioni, EMBL-EBI, Wellcome Genome Campus, Cambridge
• Sarah Teichmann, Wellcome Trust Sanger Institute, University of Cambridge  
• Dean Sheppard, University of California, San Francisco
• Rafael Kramann, University of Aachen

Partners and Funders

• Wellcome Trust
• Medical Research Council
• Chan Zuckerberg Initiative
• Guts UK
• Children's Liver Disease Foundation
• British Heart Foundation
• Tenovus Scotland
• William Rooney Research Trust
• Kidney Research UK
• Medical Research Scotland