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    Overview

    The Reynolds Lab aims to better understand immune-mediated rheumatic diseases by applying multi-omic data methods and systems immunology. We are focused on (1) identifying immune-stromal interactions that lead to tissue damage and (2) understanding the regulatory processes at the interface between tolerance and persistent inflammation.

    There is a crucial need to better understand the mechanisms driving autoimmune diseases and chronic inflammation, especially in conditions with defined triggers where some patients recover and others develop long-term issues. The research addresses gaps in knowledge about immune tolerance failure and the persistence of inflammation. Additionally, the development of fibrosis in immune-mediated diseases leads to significant morbidity, making it essential to explore tissue remodeling and potential therapeutic interventions.

    Goals

    • To support the development of therapies that can target tissue damage in rheumatic diseases and to understand how self-tolerance is regained in autoimmunity.

    Objectives

    • To explore the mechanisms underlying tissue remodeling, damage and fibrosis focusing on conditions such as ANCA-associated vasculitis and Giant Cell Arteritis.
    • To investigate immune tolerance, focusing on Lyme arthritis and immune-checkpoint inhibitor induced arthritis

    Current need for research

    • One of the main causes of morbidity and mortality in rheumatic diseases is tissue damage and fibrosis due to inflammation. While we can target this inflammation directly there is an unmet need for non-immunosuppressive therapies that prevent this damage directly.
    • There is a crucial need to better understand why immune-mediated rheumatic diseases resolve in some individuals, while in others persists and causes ongoing morbidity. This is highlighted by certain diseases with a clearly defined trigger and where a proportion of patients recover while others develop chronic inflammation. This research addresses gaps in knowledge about immune tolerance failure and the persistence of inflammation.

    Research Projects

    • Understanding Immune Persistence: Research focuses on why immune responses persist in rheumatic diseases with defined triggers (Lyme arthritis, immune-checkpoint inhibitor-induced arthritis).
    • Tissue Remodeling and Fibrosis: Studying intimal hyperplasia in Giant Cell Arteritis and fibrosis in ANCA-associated vasculitis to address the leading causes of disease-related morbidity.

    The research has significant clinical implications, particularly in identifying new therapeutic targets and developing strategies to restore immune homeostasis in autoimmune diseases. Insights gained from this research could lead to improved treatments for chronic inflammation and tissue damage in rheumatic diseases, potentially reducing disease progression and improving patient outcomes. Specifically, understanding fibrosis and tissue remodeling could result in novel approaches to treating vasculitis-related conditions, which are often major contributors to morbidity.

    Meet Our Team

    Principal Investigator

    Gary Reynolds, MBBS, PhDGary Reynolds, MBBS, PhD




    Research Team

    • Wamia Said – Data Analyst
    • Adrien Antoinette, PhD - Postdoctoral Fellow
    • Sergio Aguilar Fernandez, PhD – Postdoctoral Fellow

    Publications

    • Reynolds G*, Vegh P*, Fletcher J*, Poyner EFM*, Stephenson E, Goh I, Botting RA, Huang N, Olabi B, Dubois A, Dixon D, Green K, Maunder D, Engelbert J, Efremova M, Polański K, Jardine L, Jones C, Ness T, Horsfall D, McGrath J, Carey C, Popescu DM, Webb S, Wang XN, Sayer B, Park JE, Negri VA, Belokhvostova D, Lynch MD, McDonald D, Filby A, Hagai T, Meyer KB, Husain A, Coxhead J, Vento-Tormo R, Behjati S, Lisgo S, Villani AC, Bacardit J, Jones PH, O'Toole EA, Ogg GS, Rajan N, Reynolds NJ, Teichmann SA, Watt FM, Haniffa M. Developmental cell programs are co-opted in inflammatory skin disease. Science. 2021 Jan 22;371(6527): eaba6500.
    • Stephenson E*, Reynolds G*, Botting RA*, Calero-Nieto FJ*, Morgan MD*, Tuong ZK*, Bach K, Sungnak W*, Worlock KB, Yoshida M, Kumasaka N, Kania K, Engelbert J, Olabi B, Spegarova JS, Wilson NK, Mende N, Jardine L, Gardner LCS, Goh I, Horsfall D, McGrath J, Webb S, Mather MW, Lindeboom RGH, Dann E, Huang N, Polanski K, Prigmore E, Gothe F, Scott J, Payne RP, Baker KF, Hanrath AT, Schim van der Loeff ICD, Barr AS, Sanchez-Gonzalez A, Bergamaschi L, Mescia F, Barnes JL, Kilich E, de Wilton A, Saigal A, Saleh A, Janes SM, Smith CM, Gopee N, Wilson C, Coupland P, Coxhead JM, Kiselev VY, van Dongen S, Bacardit J, King HW; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID-19 BioResource Collaboration, Rostron AJ, Simpson AJ, Hambleton S, Laurenti E, Lyons PA, Meyer KB, Nikolić MZ, Duncan CJA, Smith KGC, Teichmann SA, Clatworthy MR, Marioni JC, Göttgens B, Haniffa M. Single-cell multi-omics analysis of the immune response in COVID-19. Nat Med. 2021 May;27(5):904-916
    • Villani AC, Satija R, Reynolds G, Sarkizova S, Shekhar K, Fletcher J, Griesbeck M, Butler A, Zheng S, Lazo S, Jardine L, Dixon D, Stephenson E, Nilsson E, Grundberg I, McDonald D, Filby A, Li W, De Jager PL, Rozenblatt-Rosen O, Lane AA, Haniffa M, Regev A, Hacohen N. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science. 2017 Apr 21;356(6335):eaah4573.