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Lynch Lab

The human skin is a complex three-dimensional organ composed of in excess of 20 cell types. It comprises a thin outer layer, the epidermis and a thicker fibrous layer, the dermis. Single cell genomics has revealed that that many of these cell types can be subdivided into discrete subpopulations however the spatial relationships of these cellular populations and their function remain poorly understood. We are combining single cell genomics with spatial genomic approaches (in situ sequencing, spatial transcriptomics etc) to decipher these relationships in both health and disease. We are particularly interested in fibroblasts – cells responsible for the synthesis and maintenance of extracellular matrix elements and in ongoing work we are developing cell therapy approaches to the treatment of abnormal wound healing and scarring. The lab additionally has an interest in the application of artificial intelligence methods within clinical dermatology.

Members

Magnus Lynch

Magnus Lynch

Group Leader

Lynch-project_singlecell

Single cell and spatial genomics of human skin

We are interested in the mechanisms by which cellular identity is established and maintained in three-dimensional mammalian tissues and how these processes are perturbed in disease states. We have employed a combination of spatial and single cell transcriptional profiling to understand cell types present in the human skin. We have a particular interest in fibroblast subpopulations that are present within the human dermis. An objective of future work is to combine single cell transcriptomic and epigenetic profiling with functional analysis to understand cell populations in both health and disease.

Lynch-project_ai

Artificial intelligence in Dermatology

Artificial intelligence and data-driven health has the potential to transform the way that clinical medicine is practiced leveraging insights from large cohorts of patients to improve diagnosis and treatment of disease. We are applying artificial intelligence approaches within clinical dermatology. We are particularly interested in skin cancer, cutaneous allergy and disease severity assessment and stratification for inflammatory skin diseases such as psoriasis.

  • Ganier C, Harun N, Peplow I, Du-Harper X, Arthurs C, Watt FM, Lynch MD. ACE2 expression is detectable in keratinocytes, cutaneous appendages and blood vessels by multiplex RNA in situ hybridization. Adv Skin Wound Care, 2021. In Press.
  • Lakhan M, Lynch MD. Skin Pigmentation. Medicine 2021 (Review) DOI:https://doi.org/10.1016/j.mpmed.2021.04.010
  • Developmental cell programs are co-opted in inflammatory skin disease. Reynolds G, Vegh P, Fletcher J,… Lynch M,…Teichmann S, Watt F, Haniffa M. Science 2021 371(6527):eaba6500
  • Wan B, Ganier C, Du-Harpur X, Harun N, Watt F, Patalay R, Lynch MD. Applications and future directions for Optical Coherence Tomography in Dermatology (review). British Journal of Dermatology. In Press
  • Du-Harpur X, Arthurs C, Ganier C, Woolf RT, Laftah Z,Lakhan, MK, Salam A, Wan B, Watt FM, Luscombe NM, Lynch MD. Clinically-relevant vulnerabilities of deep machine learning systems for skin cancer diagnosis. Journal of Investigative Dermatology 2020 S0022.
  • Du-Harpur X, Luscombe N, Watt FM, Lynch MD. What is AI? Applications of artificial intelligence to dermatology. British Journal of Dermatology 2020 183:423.
  • Teo Y, McFadden J, White I, Lynch MD and Banerjee P. Allergic Contact Dermatitis in Atopic Individuals: Results of a 30-year Retrospective Study. Contact Dermatitis 2020. In Press *equal contribution
  • van de Lagemaat LN, Flenley M, Lynch MD, Garrick D, Tomlinson SR, Kranc KR, Vernimmen D. CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands. v Epigenetics Chromatin. 2018 Oct 6;11(1):59.
  • Philippeos C, Telerman S, Oulès B, Pisco A, Shaw T, Elgueta R, Lombardi G, Driskell R, Soldin M, Lynch MD and Watt F, Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations. 2018 138:811. *joint senior author
  • Lynch MD, Watt FM Fibroblast heterogeneity: Implications for human disease (review). Journal of Clinical Investigation 2018. 128:26-35.
  • Lynch MD, Lynch CNS, Craythorne E, Liakath-Ali K, Mallipeddi R, Barker JN and Watt FM. Spatial constraints govern competition of mutant clones in human epidermis. Nature Communications 2017. 8:1119.
  • Lynch MD, McFadden JP, White JM, Banerjee P, White IR. Age-specific profiling of cutaneous allergy at high temporal resolution suggests age-related alterations in regulatory immune function. Journal of Allergy and Clinical Immunology 2017. 140:1451-1453
  • Lynch MD, White JM, McFadden JP, Wang Y, White IR, Banerjee P. A dynamic landscape of allergen associations in delayed-type cutaneous hypersensitivity. British Journal of Dermatology 2017 176:184.
  • Jeziorska DM, Murray RJS, De Gobbi M, Gaentzsch R, Garrick D, Ayyub H, Chen T, Li E, Telenius J, Lynch MD, Graham B, Smith AJH, Lund JN, Hughes JR, Higgs DR, Tufarelli C. DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease. Proc Natl Acad Sci. 2017. 114:E7526-E7535.
  • Alwan W, Lynch M, McFadden J, White IR, Banerjee P. Patch testing in psoriasis patients: results of a 30-year retrospective cohort study. British Journal of Dermatology 2017 in press
  • Lynch MD, Ali F, Mallipeddi R. A pedunculated nasal nodule. British Medical Journal 2017 356:j763.
  • Lynch MD, Bashir S. Applications of Platelet-Rich-Plasma in Dermatology: A Critical Appraisal of the Literature. J Dermatol Treatment 2016. 27:285
  • Lynch MD, Sears A, Cookson H, Lew T, Laftah Z, Orrin L, Zuckerman M, Creamer D, Higgins E. Disseminated Coxsackievirus A6 affecting children with atopic dermatitis. Clin Exp Dermatol. 2014. 40:525
  • Lynch MD, Cliffe J, Morris-Jones R. Authors' reply to Cockayne and colleagues. BMJ 2014 348:g4092.
  • Lynch MD, Cliffe J, Morris-Jones R. Management of cutaneous viral warts. BMJ. 2014 348:g3339. Review.
  • Hughes JR, Roberts N, McGowan S, Hay D, Giannoulatou E, Lynch MD, De Gobbi M, Taylor S, Gibbons R, Higgs DR. Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment. Nat Genet. 2014 46:205-12.
  • Lynch MD, Smith AJ, de Gobbi M, Flenley M, Hughes JR, Vernimmen D, Ayyub H, Sharpe JA, Sloane-Stanley JA, Sutherland L, Meek S, Burdon T, Gibbons RJ, Garrick D, Higgs DR. An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment. EMBO Journal Nov 2011
  • Vernimmen D. Lynch MD, de Gobbi M, Garrick D, Sharpe JA, Sloane-Stanley JA, Smith AJ, Higgs DR. Polycomb Eviction as a New Distant Enhancer Function. Genes & Dev, 2011 25:1583-8.
  • Kowalczyk MS, Hughes JR, Lynch MD, Garrick D, Sharpe JA, Sloane-Stanley JA, McGowan SJ, De Gobbi M, Hosseini M, Vernimmen D, Brown JM, Gray NE, Collavin L, Gibbons RJ, Flint J, Taylor S, Buckle VJ, Milne TA, Wood WG, Higgs DR. Intragenic enhancers act as alternative promoters. Mol Cell 2012 45:447-458 *equal contribution
  • De Gobbi M, Garrick D, Lynch MD, Vernimmen D, Hughes JR, Goardon N, Luc S, Lower KM, Sloane-Stanley JA, Pina C, Soneji S, Renella R, Enver T, Taylor S, Jacobsen SEW, Vyas P, Gibbons RJ, Higgs DR. Generation of Bivalent Chromatin Domains During Cell Fate Decisions. Epigenetics and Chromatin, 2011 4:9
  • Garrick D, De Gobbi M, Lynch MD, Higgs DR. Switching genes on and off in haemopoiesis. Biochem Soc Trans. 2008 36:613-8. (Review)
  • Lynch MD, Cariati M, Purushotham AD. Breast cancer, setm cells and prospects for therapy. Breast Cancer Res. 2006 8:211. (Review)
  • Lynch MD, Jones AE, Marker A, Grant JW, Purushotham AD. Malignant eccrine poroma in breast cancer-related lymphoedema. Ann R Coll Surg Engl. 2004 86:W32-5.
  • Lynch MD. How does cellular senescence prevent cancer? DNA Cell Biol. 2006 25:69-78. Review
  • Lynch MD. The role of cellular senescence may be to prevent proliferation of neighboring cells within setm cell niches. Ann N Y Acad Sci. 2004. 1019:191-4.

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