Institute of Cellular Medicine

Staff Profile

Dr Karin Engelhardt

Research Associate

Background

Roles and Responsibilities

I am a Research Associate in the research group of Dr. Sophie Hambleton on a five-year project funded by the Sir Jules Thorn Charitable Trust, “Bringing next generation sequencing to the next generation”. 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

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).

Languages

I speak German and English.

Research

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".  

Publications