Kawasaki Disease
I have undertaken research on Kawasaki disease since the 1980’s when I identified the presence of Immune
Complexes in the blood of patients. I have lead work on the genetics, immunology, clinical recognition, and diagnosis using both RNA and protein biomarker detection. This work has led to identification of an RNA small signature which is being developed as a diagnostic test for KD with industrial partners.
Shimizu C, Eleftherohorinou H, (24 authors), Michael Levin, Jane C Burns, 2016 Genetic variation in the SLC8A1 calcium signaling pathway is associated with susceptibility to Kawasaki disease and coronary artery abnormalities, Circulation. Cardiovascular Genetics, Vol: 9, Pages: 559-568, ISSN: 1942-3268
Khor CC, Davila S, (19 authors) , Michael Levin, Jane C Burns, David Burgner, Taco W Kuijpers, Martin L Hibberd, 2011, Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease, Nature Genetics, Vol: 43, Pages: 1241-1246, ISSN: 1061-4036
Genetics and Immunology of childhood mycobacterial infection
My group has made important contributions to the understanding of the immunology of mycobacterial infection. I identified the first families with genetic susceptibility to mycobacterial infection and identified the defective gene as being interferon-gamma receptor gene. In collaboration with Professor Casanova’s group in Paris, we established that other mutations, which also caused disseminated BCG. This work initiated the field of type 1 cytokine genetic defects and provided evidence that IFNg and IL-12 pathways are central to immunity to mycobacteria. I identified a novel immune deficiency mediated by auto-antibodies against interferon-gamma further confirming the importance of the interferon-gamma pathway in susceptibility to TB.
Levin M, Newport MJ, D’Souza S, Kalabalikis P, Brown IN, Lenicker HM, Vassallo Agius P, Davies EG, Thrasher A, Klein N, Blackwell JM. Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene? Lancet 1995; 345: 79-83. (first author)
Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, Levin M. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med. 1996 Dec 26;335(26):1941-9. (senior author)
Kampmann B, Hemingway C, (15 authors), Levin M. Acquired Immune defect in the handling of Mycobacteria due to auto antibodies against Interferon Gamma. J Clin Invest. 2005 Sep 1; 115(9): 2480–2488. (senior author)
Diagnosis of childhood TB, adult TB and bacterial infections
I led an international study (UK, Malawi, Kenya, South Africa) to identify host RNA and protein biomarkers of childhood and adult TB which identified RNA expression signatures for adult TB and childhood TB. We have also used RNA expression profiling to understand mechanism in TB. I also lead a team that has pioneered diagnosis of bacterial infection and distinction from viral infection using small RNA signatures
Kaforou M, Herberg JA, Wright VJ, Coin LJM, Levin M 2017,Diagnosis of bacterial infection using a 2-transcript host RNA signature in febrile infants 60 days or younger, JAMA: Journal of the American Medical Association, Vol: 317, Pages: 1577-1578, ISSN: 0098-7484
Anderson ST, Kaforou M, Brent AJ, (20 authors), Levin M, Eley B. Diagnosis of childhood tuberculosis and host RNA expression in Africa. N Engl J Med, 2014. 370(18): p.1712-23. (joint senior author)
Kaforou M, Wright VJ, (19 authors), Levin M. Detection of tuberculosis in HIV-infected and -uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med, 2013. 10(10): p.e1001538. (joint senior author)
von Both U, (11 authors), Levin M. Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System for Intracellular Survival. Sci Rep. 2018 Jan 12;8(1):661. doi: 10.1038/s41598-017-18528-y. (senior author)
Meningococcal sepsis and meningitis
My group has identified key pathophysiological mechanisms in meningococcal sepsis, including the role of capillary leak and coagulopathy and myocardial depression Our program of genetic research on meningococcal disease led to the identification of key roles in susceptibility and severity of meningococcal disease for mannose binding protein , plasminogen activator inhibitor ,and Complement Factor H. I have lead a number of placebo-controlled treatment trials investigating new treatments of meningococcal sepsis.
Faust SN, Levin M et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med Vol 345, No 6 August 9, 2001 pp408-416
Pathan N, Hemingway C.A.,(11 authors), Levin M Identification of interleukin 6 as a major mediator of myocardial dysfunction in meningococcal septic shock. The Lancet, Vol 363 Issue 9404 pp 203-209 17 Jan 2004 (senior author)
Levin M, P A Quint, et al. Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. The Lancet Vol 356; September 16 2000 pp 961-967
Davila S, Wright VJ, (17 authors), Levin M, Hibberd ML, Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. Nat Genet. 2010 Sep;42(9):772-6. doi: 10.1038/ng.640.
Treatment of malaria and sepsis
I have undertaken a programme of work to understand the pathophysiology of severe malaria and septic shock inAfrica.IwasseniorauthorontheUKMRC-fundedFEASTtrialoffluidbolusresuscitationinAfricanchildren withseveremalariaorsepsis.
Maitland K, (14 authors), Levin M, Babiker AG, Gibb DM, Mortality after fluid bolus in African children with severe infection. N Engl J Med, 2011. 364(26): p.2483-95.
Levin M, Cunnington AJ, Wilson C, et al. Effects of saline or albumin fluid bolus in resuscitation: Evidence from re-analysis of the feast trial. Lancet Respir Med 2019; 7(7): 581-93.
Collaborators
Professor Taco Kuijpers, Academic Medical Centre, Amsterdam(Academisch Medisch Centrum bij de Universiteit van Amsterdam), Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2016 - 2017
Jan HazelzetMarieke Emonts, Erasmus UniversityMedical Center Rotterdam, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2016 - 2017
TBVI Consortium, TB vaccine research, 2015 - 2018
Professor Andrew Pollard, University of Oxford, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Dr Enitan Carroll, The University of Liverpool, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Ronald de GrootPeter Hermans, Stichting Katholieke Universiteit, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Dr Werner Zenz, The Medical University of Graz, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Federico Martinon-TorresAntonio Salas Ellacuriaga, Fundacion IDICHUS, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
James Clough, Oxford Gene Technology, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Dr Colin Fink, Micropathology Ltd, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Dr Suzanne AndersonDr Kalifa Bojang, Medical Research Council The Gambia, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Rino RappuoliDavide Serruto, Novartis Vaccines and Diagnostics srl (NVD), Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Professor Martin Hibberd, Genome Institute of Singapore, Genetic basis of susceptibility to infection and severity of disease, major bacterial infections of childhood, 2011 - 2017
Professor Paiboon Sithithaworn and team, Khon Kaen University Liver Fluke and Cholangiocarcinoma Centre, Liver fluke and cholangiocarcinoma biomarkers (part of the Wellcome Global Centre at Imperial), 2010
Professor David Beatty, Red Cross Children's Hospital and University of Cape Town
Guest Lectures
For the front line ID/Immumo doc: whose genomeshould I sequence?, Infection & Immunity in Children 2016, University of Oxford, 2016
Gene Expression, UCLH - Evelina Neonatal Infection Symposium, UCLH-Evelina Children's Hospital, 2016
Meningococcal Disease, Journal of Family Health / RCPCH, 2015
"The diagnostic promise of transcriptomics in TB", British Thoracic Society, 2015
Susceptibility to Meningococcal Infection, European Society for Immunodeficiencies(ESID), 2014
Functional Genomics in African Children, ICAAC (American Society for Microbiology), 2014
What can genomics tell us about the acutely ill child with a severe infection?, Otto Wolff Memorial Lecture for Royal Society of Medicine, 2014
Advances in treatment of Kawasaki Syndrome, European Society of Paediatric Infectious Diseases (ESPID), 2014
Keynote speaker. Mini-symposium on translational genomics., St Mary's hospital, 2013
French paediatric hematology-immunology society meeting, 2002
European Society for Paediatric Research, 2002
Genetic susceptibility to infectious diseases, European Society for Paediatric Infectious Diseases (ESPID)
Research Staff
Hoggart,C
Tudor-Williams,G
Research Student Supervision
Alavi,A, Tailored MRI protocols are the ultimate imaging tools in the diagnostic and diferential diagnostic of musculoskeletal infection in children
Basu-Roy,R, Protection from Mycobacterium tuberculosis infection: Learning from exposed but uninfected children
Gliddon,H, Engineering a novel tuberculosis diagnostic test using nanomaterial-based detection of a host blood gene expression signature”.
Kavanagh,J, The role of the airway microbiome on host response to viral infections.
MacDermott,N, Are there genetic determinants of clinical phenotype and disease outcome for Ebola Virus Disease (EVD)?
Mashbat,M, Investigating single gene disorders of childhood infectious disease
Menikou,S, Identification of the causative agent of Kawasaki Disease through isolation and characterization of antigens within immune complexes
Morris,T, Serum biomarkers in human tuberculosis: discoveries and applications
Rahman,R, Identifying Mendelian single gene defects of invasive meningococcal disease
von Both,U, ESPID Fellow: Childhood tuberculosis: A new acquired immunodeficiency syndrome.