Dr Karin Engelhardt
- Email: email@example.com
- Telephone: 0191-208-2750
- Address: Institute of Cellular Medicine
3rd Floor William Leech Building
Newcastle upon Tyne
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.
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
Newcastle University, 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.
I am a member of the European Society of Primary Immunodeficiencies (ESID).
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".
- Engelhardt K, McGhee S, Winkler S, Sassi A, Woellner C, Lopez-Herrera G, Chen A, Kim H, Lloret M, Schulze I, Ehl S, Thiel J, Pfeifer D, Veelken H, Niehues T, Siepermann K, Weinspach S, Reisli I, Keles S, Genel F, Kutuculer N, Camcioǧlu Y, Somer A, Karakoc-Aydiner E, Barlan I, Gennery A, Metin A, Degerliyurt A, Pietrogrande M, Yeganeh M, Baz Z, Al-Tamemi S, Klein C, Puck J, Holland S, McCabe E, Grimbacher B, Chatila T. Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. Journal of Allergy and Clinical Immunology 2009, 124(6), 1289-1302.e4.
- Schepp J, Chou J, Skrabl-Baumgartner A, Arkwright PD, Engelhardt KR, Hambleton S, Morio T, Rother E, Warnatz K, Geha R, Grimbacher B. 14 Years after Discovery: Clinical Follow-up on 15 Patients with Inducible Co-Stimulator Deficiency. Frontiers in Immunology 2017, 8.
- Duncan CJA, Dinnigan E, Theobald R, Grainger A, Skelton AJ, Hussain R, Willet JDP, Swan DJ, Coxhead J, Thomas MF, Thomas J, Zamvar V, Slatter MA, Cant AJ, Engelhardt KR, Hambleton S. Early-onset autoimmune disease due to a heterozygous loss-of-function mutation in TNFAIP3 (A20). Annals of the Rheumatic Diseases 2018, 77(5), 783-786.
- 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. Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing. Journal of Clinical Immunology 2017, 37(1), 42-50.
- Singh Dang T, 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, Santibanez Koref M, Reynard LN, Ali S, Hambleton S. Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency. Journal of Clinical Immunology 2016, 36(2), 117-122.
- 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. Erratum to: Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency (vol 36, pg 117, 2016). 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. Hematopoietic stem cell transplantation for CTLA4 deficiency. Journal of ALlergy and Clinical Immunology 2016, 138(2), 615-619.
- Robertson N, Engelhardt K, Morgan N, Barge D, Cant A, Hugues S, Abinun M, Xu YB, Koref M, Arkwright P, Hambleton S. A Novel 10bp Frameshift Deletion In ICOS In Two Patients With Combined Immunodeficiency. In: UK PIN 2015. 2015, Belfast, Northern Ireland: Wiley-Blackwell Publishing Ltd.
- Robertson N, Engelhardt KR, Morgan NV, Barge D, Cant AJ, Hughes SM, Abinun M, Xu YB, Koref MS, Arkwright PD, Hambleton S. Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis. Journal of Clinical Immunology 2015, 35(7), 598-603.
- Al Qayoodhi A, Hambleton S, Hattersley AT, Cant AJ, Flanagan SE, Engelhardt K, Swan D, Willet J, Xu YB, Koref MS, Leahy TR. Autoimmunity In STAT3 Gain Of Function Mutations; Broadening The Phenotype. In: UKPIN 2015 Meeting. 2015, Belfast, Northern Ireland: Wiley-Blackwell Publishing Ltd.
- 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. DOCK8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients. Journal of Clinical Immunology 2015, 35(2), 189-198.
- Milner JD, Vogel TP, Forbes L, Ma CA, Stray-Pedersen A, Niemela JE, Lyons JJ, Engelhardt KR, Zhang Y, Topcagic N, Roberson EDO, Matthews H, Verbsky JW, Dasu T, Vargas-Hernandez A, Varghese N, McClain KL, Karam LB, Nahmod K, Makedonas G, Mace EM, Sorte HS, Perminow G, Rao VK, O'Connell MP, Price S, Su HC, Butrick M, McElwee J, Hughes JD, Willet J, Swan D, Xu Y, Santibanez-Koref M, Slowik V, Dinwiddie DL, Ciaccio CE, Saunders CJ, Septer S, Kingsmore SF, White AJ, Cant AJ, Hambleton S, Cooper MA. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood 2015, 125(4), 591-599.
- 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. Human IFNAR2 deficiency: lessons for antiviral immunity. Science Translational Medicine 2015, 7(307), 307ra154.
- Duncan C, Mohamad S, Young D, Skelton A, Leahy R, Munday D, Butler K, Morfopoulou S, Brown J, Hubank M, Connell J, Gavin P, McMahon C, Dempsey E, Lynch N, Jacques T, Valappil M, Cant A, Engelhardt K, Breuer J, Randall R, Hambleton S. Human IFNAR2 Deficiency: Lessons For Antiviral Immunity. In: UKPIN 2015 Meeting. 2015, Belfast, Northern Ireland: Wiley-Blackwell Publishing Ltd.
- Engelhardt KR, Xu YB, Grainger A, Batacchi MGCG, Swan DJ, Willet JDP, Abd Hamid IJ, Agyeman P, Barge D, Bibi S, Jenkins L, Flood T, Abinun M, Slatter M, Gennery AR, Cant AJ, Koref MS, Hambleton S. Identification Of Heterozygous Single- And Multi-exon Deletions In IL7R By Whole Exome Sequencing. In: UKPIN 2015 Meeting. 2015, Belfast, Northern Ireland: Wiley-Blackwell Publishing Ltd.
- Engelhardt KR, Gertz ME, Keles S, Schaffer AA, Sigmund EC, Glocker C, Saghafi S, Pourpak Z, Ceja R, Sassi A, Graham LE, Massaad 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, Yilmaz M, Genel F, Aytekin C, Kutukculer N, Somer A, Kilic M, Reisli I, Camcioglu Y, Gennery AR, Cant AJ, Jones A, Gaspar BH, 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. The extended clinical phenotype of 64 patients with dedicator of cytokinesis 8 deficiency. Journal of Allergy and Clinical Immunology 2015, 136(2), 402-412.
- 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. The Extended Clinical Phenotype of 58 Patients with Dock8 Deficiency. 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. ZNF341 controls STAT3 expression and thereby immunocompetence. Science Immunology 2018, 3(24).