Dr Delphine Cuchet- Lourenco

Understanding biological mechanisms involved in mycobacterial infection using in vitro cell models:

In this project we study healthy volunteers participating in Cambridge BioResource. We isolate immune cells from blood samples of the volunteers and use in vitro models of mycobacterial infection and transcriptome analyses to investigate mechanisms that human cells utilise to contain and eliminate mycobacteria. We compare genetic information from different people and their immune cell responses upon infection in vitro. Our goal is to discover sequence variants, genes and biological pathways that are involved in protection from mycobacteria.

Key Projects:

(1) Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration (Nature Genetics volume 47, pages 523–527 (2015)

Department of Medicine, University of Cambridge, Cambridge, UK.
James Curtis, Helen L Zenner, Delphine Cuchet-Lourenço, Changxin Wu, Mailis Maes, Ali Alisaac, Emma Stebbings, Liliya Kopanitsa & Sergey Nejentsev
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Yang Luo, Jimmy Z Liu & Jeffrey C Barrett
University College London Genetics Institute, University College London, London, UK.
Kitty Lo & Vincent Plagnol
Samara Oblast Tuberculosis Dispensary, Samara, Russia.
Olga Ignatyeva
Robert Koch Institute, Berlin, Germany.
Yanina Balabanova
Imperial College London, London, UK.
Yanina Balabanova, Vladyslav Nikolayevskyy & Francis Drobniewski
Queen Mary University of London, London, UK.
Yanina Balabanova, Vladyslav Nikolayevskyy & Francis Drobniewski
Public Health England National Mycobacterium Reference Laboratory, London, UK.
Vladyslav Nikolayevskyy & Francis Drobniewski
Cologne Center for Genomics, University of Cologne, Cologne, Germany.
Ingelore Baessmann & Peter Nürnberg
Department of Molecular Medicine, Bernhard Nocht Institute for Topical Medicine, Hamburg, Germany.
Thorsten Thye, Christian G Meyer & Rolf D Horstmann
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Peter Nürnberg
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
Peter Nürnberg

(2) Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. (Science. 2018 Aug 24;361(6404):810-813). Cuchet-Lourenço D 1, Eletto D 1, Wu C 1, Plagnol V 2, Papapietro O 1, Curtis J 1, Ceron-Gutierrez L 3, Bacon CM 4,5, Hackett S 6, Alsaleem B 7, Maes M 1, Gaspar M 1, Alisaac A 1,8, Goss E 1, AlIdrissi E 9, Siegmund D 10, Wajant H 10, Kumararatne D 3, AlZahrani M S9, Arkwright PD 11, Abinun M 12, Doffinger R 3, Nejentsev S 13.

1
Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
2
University College London Genetics Institute, University College London, London, UK.
3
Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, UK.
4
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
5
Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
6
Paediatric Immunology Department, Birmingham Heartland Hospital, Birmingham, UK.
7
Children's Hospital, King Fahad Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
8
Faculty of Applied Medical Sciences, Albaha University, Albaha, Kingdom of Saudi Arabia.
9
Children's Hospital, University of King Saud for Health Sciences, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia.
10
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
11
University of Manchester, Royal Manchester Children's Hospital, Manchester, UK.
12
Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
13
Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.