缅北禁地

Roles and Responsibilities

I am a Research Associate in the research group of Prof. Sophie Hambleton on a five-year project funded by a Wellcome Trust Investigator Award to Prof. Hambleton, “The Troubled Immune System: Molecular Origins of Early Onset Immune Dysregulation”. I am responsible for oversight and delivery of research described in this proposal, specifically the validation and mechanistic exploration of novel genetic variants implicated in primary immunodeficiency disease. I contribute to the dissemination of results through presentations to clinicians and other researchers and through the writing up of the findings in clinical reports. I have a co-supervisory role for a PhD student and am involved in supervision of final year undergraduate research projects.

Qualifications

PhD in Virology, from the University of Freiburg, Germany.

Diplom (First class honours degree) in Biochemistry, from the Free University of Berlin, Germany.

Previous positions and Research

缅北禁地, Institute of Cellular Medicine, UK: Research Associate in the PID group of Prof. Sophie Hambleton. I participated in a five-year project funded by the Sir Jules Thorn Charitable Trust, “Bringing next generation sequencing to the next generation”, identifying mutations in known and novel PID genes in past and present patients with inborn errors of the immune system.

University of Freiburg, Center for Chronic Immunodeficiencies (CCI), Germany: Research Associate in the group of Prof. Bodo Grimbacher. I looked for mutations in the IL-10 and IL-10 receptor genes in patients with early-onset-colitis, and worked as a "scientific writer" contributing to writing reviews and book chapters about primary immunodeficiencies, as well as grant proposals and reports.

University College London, Department of Immunology and Molecular Pathology, UK: Research Associate in the group of Prof. Bodo Grimbacher. I was searching for disease-causing genes in Hyper-IgE syndrome by linkage analysis and found mutations in DOCK8 to be the most common cause in the autosomal-recessive form of the disease. I identified further patients with DOCK8 mutations by sequencing and described the clinical phenotype of DOCK8 deficiency.

University of Oxford, Sir William Dunn School of Pathology, UK: Postdoctoral Marie Curie Research Fellow in the group of Dr. Thomas Harder. I studied the composition and dynamics of T cell receptor signalling complexes using biochemical analysis of native signalling assemblies purified by a novel immunoisolation procedure.

University of Freiburg, Institute for Medical Microbiology and Hygiene, Germany: Research Associate (PhD student) in the group of Prof. Peter Staeheli. I analysed Borna disease virus-specific CD8 T cells isolated from brains of diseased mice by functional assays and FACS analysis and conducted a vaccination study.

Weizmann Institute of Science, Rehovot, Israel: Research Associate (Diplom student) in the group of Prof. Yosef Yarden. I studied the cross-talk between signal transduction pathways of cytokines and ErbB-2, a protein that is overexpressed on the surface of many malignant cells. 

Memberships

I am a member of the European Society of Primary Immunodeficiencies (ESID) and of the British Society for Immunology (BSI).

Languages

I speak German and English.

We are looking for disease-causing variants in patients with various primary immunodeficiency diseases by Whole Exome Sequencing (WES). Variants are filtered to include those that are rare (<1%) and predicted deleterious. In a first instance, we focus on genes known to be mutated in primary immunodeficiency diseases (PID genes), followed by other genes relevant to the immune system. Convincing variants are validated by Sanger sequencing and assessed by functional assays.

We find WES to be a successful way to identify mutations in known PID genes as part of a diagnostic work up. In addition, we are able to find mutations in known disease genes that cannot be detected by conventional methods, e.g. heterozygous multi-exon deletions. We also identified a disease-causing mutation in a gene linked to a particular disease phenotype in a patient who only had partial overlap with the clinical picture and thus would have been not considered for screening of this particular gene.  

Finally, we identify novel disease genes whose function in the immune system can be further explored having a human "knock-out".  

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• Engelhardt KR, Xu Y, Grainger A, Germani Batacchi MGC, Swan DJ, Willet JDP, Abd Hamid IJ, Agyeman P, Barge D, Bibi S, Jenkins L, Flood TJ, Abinun M, Slatter MA, Gennery AR, Cant AJ, Santibanez Koref M, Gilmour K, Hambleton S. . Journal of Clinical Immunology 2017, 37(1), 42-50.
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• Dang TS, Willet JDP, Griffin HR, Morgan NV, O'Boyle G, Arkwright PD, Hughes SM, Abinun M, Tee LJ, Barge D, Engelhardt KR, Jackson M, Cant AJ, Maher ER, Koref MS, Reynard LN, Ali S, Hambleton S. . Journal of Clinical Immunology 2016, 36(3), 336-337.
• Slatter MA, Engelhardt KR, Burroughs LM, Arkwright PD, Nademi Z, Skoda-Smith S, Hagin D, Kennedy A, Barge D, Flood T, Abinun M, Wynn RF, Gennery AR, Cant AJ, Sansom D, Hambleton S, Torgerson TR. . Journal of ALlergy and Clinical Immunology 2016, 138(2), 615-619.
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• Aydin SE, Kilic SS, Aytekin C, Kumar A, Porras O, Kainulainen L, Kostyuchenko L, Genel F, Kutukculer N, Karaca N, Gonzalez-Granado L, Abbott J, Al-Zahrani D, Rezaei N, Baz Z, Thiel J, Ehl S, Marodi L, Orange JS, Sawalle-Belohradsky J, Keles S, Holland SM, Sanal O, Ayvaz DC, Tezcan I, Al-Mousa H, Alsum Z, Hawwari A, Metin A, Matthes-Martin S, Honig M, Schulz A, Picard C, Barlogis V, Gennery A, Ifversen M, van Montfrans J, Kuijpers T, Bredius R, Duckers G, Al-Herz W, Pai S-Y, Geha R, Notheis G, Schwarze C-P, Tavil B, Azik F, Bienemann K, Grimbacher B, Heinz V, Gaspar HB, Aydin R, Hagl B, Gathmann B, Belohradsky BH, Ochs HD, Chatila T, Renner ED, Su H, Freeman AF, Engelhardt K, Albert MH. . Journal of Clinical Immunology 2015, 35(2), 189-198.
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• Duncan CJA, Mohamad SMB, Young DF, Skelton AJ, Leahy TR, Munday DC, Butler KM, Morfopoulou S, Brown JR, Hubank M, Connell J, Gavin PJ, McMahon C, Dempsey E, Lynch NE, Jacques TS, Valappil M, Cant AJ, Breuer J, Engelhardt KR, Randall RE, Hambleton S. . Science Translational Medicine 2015, 7(307), 307ra154.
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• Engelhardt KR, Gertz EM, Schaffer AA, Keles S, Sigmund EC, Ceja R, Sassi A, Graham L, Masaad MJ, Mellouli F, Ben-Mustapha I, Khemiri M, Kilic SS, Etzioni A, Freeman AF, Thiel J, Schulze I, Al-Herz W, Metin A, Sanal O, Tezcan I, Yeganeh M, Niehues T, Dueckers G, Weinspach S, Patiroglu T, Unal E, Dasouki M, Yilamaz M, Genel F, Aytekin C, Kutukculer N, Somer A, Kilic M, Reisli I, Camcioglu Y, Gennery AR, Cant AJ, Jones A, Gaspar HB, Arkwright PD, Pietrogrande MC, Baz Z, Al-Tamemi S, Lougaris V, Lefranc G, Megarbane A, Boutros J, Galal N, Bejaoui M, Barbouche MR, Geha RS, Chatila TA, Grimbacher B. . In: European Society for Immunodeficiencies. 2014, Prague, Czech Republic: Springer.
• Frey-Jakobs S, Hartberger JM, Fliegauf M, Bossen C, Wehmeyer ML, Neubauer JC, Bulashevska A, Proietti M, Fröbel P, Nöltner C, Yang L, Rojas-Restrepo J, Langer N, Winzer S, Engelhardt KR, Glocker C, Pfeifer D, Klein A, Schäffer AA, Lagovsky I, Lachover-Roth I, Béziat V, Puel A, Casanova JL, Fleckenstein B, Weidinger S, Kilic SS, Garty BZ, Etzioni A, Grimbacher B. . Science Immunology 2018, 3(24).
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• Spegarova JS, Lawless D, Mohamad SMB, Engelhardt KR, Doody G, Shrimpton J, Rensing-Ehl A, Ehl S, Rieux-Laucat F, Cargo C, Griffin H, Mikulasova A, Acres M, Morgan NV, Poulter JA, Sheridan EG, Chetcuti P, O'Riordan S, Anwar R, Carter C, Przyborski S, Windebank K, Cant AJ, Lako M, Bacon CM, Savic S, Hambleton S. . Blood 2020, 136(9), 1055-1066.
• Lum SH, Anderson C, McNaughton P, Engelhardt K, MacKenzie B, Watson H, Al-Mousa H, Al-Herz W, Al-Saud B, Mohammed R, ALZahrani D, Alghamdi HA, Goronfolah L, Nademi Z, Habibolla S, Flinn AM, Shillitoe B, Owens S, Williams E, Emonts M, Hambleton S, Abinun M, Flood T, Cant A, Gennery AR, Slatter M. . Blood 2020, 135(12), 954-973.
• Anzilotti C, Swan DJ, Boisson B, Deobagkar-Lele M, Oliveira C, Chabosseau P, Engelhardt KR, Xu X, Chen R, Alvarez L, Berlinguer-Palmini R, Bull KR, Cawthorne E, Cribbs AP, Crockford TL, Dang TS, Fearn A, Fenech EJ, de Jong SJ, Lagerholm C, Ma CS, Sims D, Van Den Berg B, Xu Y, Cant AJ, Kleiner G, Leahy TR, de laMorena MT, Puck JM, Shapiro RS, van der Burg M, Chapman JR, Christianson JC, Davies B, McGrath JA, Przyborski S, Santibanez Koref M, Tangye SG, Werner A, Rutter GA, Padilla-Parra S, Casanova JL, Cornall RJ, Conley ME, Hambleton S. . Nature Immunology 2019, 20, 350-361.
• Zhang Z, Gothe F, Pennamen P, James JR, McDonald D, Mata CP, Modis Y, Alazami AM, Acres M, Haller W, Bowen C, Doffinger R, Sinclair J, Brothers S, Zhang Y, Matthews H, Naudion S, Pelluard F, Alajlan H, Yamazaki Y, Notarangelo LD, Thaventhiran JED, Engelhardt KR, Al-Mousa H, Hambleton S, Rooryck C, Smith KGC, Lenardo MJ. . Journal of Experimental Medicine 2019, 216(6), 1311-1327.
• Swan DJ, Aschenbrenner D, Lamb CA, Chakraborty K, Clark J, Pandey S, Engelhardt KR, Chen R, Cavounidis A, Ding Y, Krasnogor N, Carey CD, Acres M, Needham S, Cant AJ, Arkwright PD, Chandra A, Okkenhaug K, Uhlig HH, Hambleton S. . Haematologica 2019, 104(10), e483-e486.
• Duncan CJA, Thompson BJ, Chen R, Rice GI, Gothe F, Young DF, Lovell SC, Shuttleworth VG, Brocklebank V, Corner B, Skelton AJ, Bondet V, Coxhead J, Duffy D, Fourrage C, Livingston JH, Pavaine J, Cheesman E, Bitetti S, Grainger A, Acres M, Innes BA, Mikulasova A, Sun R, Hussain H, Wright R, Wynn R, Zarhrate M, Zeef LAH, Wood K, Hughes SM, Harris CL, Engelhardt KE, Crow YJ, Randall RE, Kavanagh D, Hambleton S, Briggs TA. . Science Immunology 2019, 4(42), eaav7501.
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