Dr Karen Mackenzie

We study rare genetic inflammatory conditions associated with lung inflammation to understand more about how these conditions occur, with the aim of identifying new therapeutic targets.

 

Dr Karen Mackenzie

MRC Clinician Scientist Fellow / Honorary Consultant in Clinical Genetics

  • Centre for Inflammation Research

Contact details

Group Members

  • Dr Hemant Bengani, Research Assistant
  • Saule Zubyte, PhD student (co-supervised with Professor Manu Shankar-Hari (primary supervisor) and Professor Adriano Rossi)
  • Tariro Chatiza, PhD Student (co-supervised with Dr Ian Simpson (primary supervisor) and Professor Richard Chin)

Background

Interstitial lung diseases are a broad group of conditions associated with long-term inflammation in the lung. Current treatments are limited, and more needs to be understood about why interstitial lung diseases occur so that better therapies can be developed.

Type I interferons are substances produced by the immune system and are particularly important for defence against viruses. However, if type I interferon responses are not controlled by the body then this can cause inflammation and disease. The “type I interferonopathies” are a group of genetic conditions where inflammation is associated with dysregulated type I interferon responses.

Research Overview

We focus on specific type I interferonopathies which are associated with lung inflammation. Some of the genetic alterations which can cause these conditions are now known, which enables us to investigate how these genetic alterations lead to inflammation. Our overarching aim is to further understand the immune mechanisms involved in lung inflammation to aid identification of new therapeutic targets. We anticipate that the results from this work will have relevance both to people affected by these rare inflammatory lung conditions, and to people affected by more common interstitial lung diseases.

Biographical Profile

Karen Mackenzie completed medical training (Hons) and an intercalated BSc (1st Class Hons) in Immunology at the University of Edinburgh before completing a Medical Research Council funded PhD in allergic lung disease at the Centre for Inflammation Research, Edinburgh. She spent time as a non-clinical Postdoctoral Fellow in the lab of Professor Andrew Jackson (Institute of Genetics and Cancer, Edinburgh) where she investigated immune pathways in a type I interferonopathy called Aicardi-Goutières disease (Nature, 2017). Karen then completed specialty medical training in Clinical Genetics and was awarded an MRC Clinician Scientist Fellowship.  

Karen has recently spent time in the Snoeck Lab in Columbia University, New York learning novel lung organoid techniques which she aims to establish in Edinburgh University.

Honours and Awards

  • 2018: Poster prize, The Academy of Medical Sciences Clinical Academics in Training conference
  • 2017: Poster prize, Therapeutic Tolerance Workshop, Newcastle University
  • 2011: Poster prize, MRC Centre for Inflammation Research
  • 2009: Highly commended in the MRC Max Perutz Science Writing Prize
  • 2008-2011: MRC Clinical Research Training Fellowship

Other Responsibilities

Honorary Consultant in Clinical Genetics, Western General Hospital, Edinburgh

Collaborators

Publications

Selected Publications

Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling. Lepelley A, Martin-Niclós MJ, Le Bihan M, Marsh JA, Uggenti C, Rice GI, Bondet V, Duffy D, Hertzog J, Rehwinkel J, Amselem S, Boulisfane-El Khalifi S, Brennan M, Carter E, Chatenoud L, Chhun S, Coulomb l'Hermine A, Depp M, Legendre M, Mackenzie KJ, Marey J, McDougall C, McKenzie KJ, Molina TJ, Neven B, Seabra L, Thumerelle C, Wislez M, Nathan N, Manel N, Crow YJ, Frémond ML. J Exp Med. 2020 Nov 2;217(11):e20200600. doi: 10.1084/jem.20200600.

cGAS surveillance of micronuclei links genome instability to innate immunity.Mackenzie KJ, Carroll P, Martin CA, Murina O, Fluteau A, Simpson DJ, Olova N, Sutcliffe H, Rainger JK, Leitch A, Osborn RT, Wheeler AP, Nowotny M, Gilbert N, Chandra T, Reijns MAM, Jackson AP.Nature. 2017 Aug 24;548(7668):461-465. doi: 10.1038/nature23449.

Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response.Mackenzie KJ, Carroll P, Lettice L, Tarnauskaitė Ž, Reddy K, Dix F, Revuelta A, Abbondati E, Rigby RE, Rabe B, Kilanowski F, Grimes G, Fluteau A, Devenney PS, Hill RE, Reijns MA, Jackson AP.EMBO J. 2016 Apr 15;35(8):831-44. doi: 10.15252/embj.201593339. Epub 2016 Feb 22.

RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. Rigby RE, Webb LM, Mackenzie KJ, Li Y, Leitch A, Reijns MA, Lundie RJ, Revuelta A, Davidson DJ, Diebold S, Modis Y, MacDonald AS, Jackson AP.EMBO J. 2014 Mar 18;33(6):542-58. doi: 10.1002/embj.201386117. Epub 2014 Feb 10.

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy.Mackenzie KJ, Nowakowska DJ, Leech MD, McFarlane AJ, Wilson C, Fitch PM, O'Connor RA, Howie SE, Schwarze J, Anderton SM.Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):E784-93. doi: 10.1073/pnas.1316178111. Epub 2014 Feb 10.

More Publications on Research Explorer Profile

Funding

MRC Clinician Scientist Fellowship 2022-2027

More information on funding at Karen Mackenzie's Research Explorer profile.

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