LCB

Hendrik Rusche

PhD student

 

 Education :

  • 10/2011-10/2014 :University of Konstanz, Konstanz, Germany, Degree: Bachelor of Science
  • 11/2014-05/2017 : University of Konstanz, Konstanz, Germany, Degree: Master of Science

Research Interest :

1. Investigating the role of (aberrant) glycosylation in autoimmune diseases and cancer by mass spectrometry

The inflammatory disease multiple sclerosis (MS) is characterized by demyelination in the central nervous system, supposedly linked to autoimmune reactions and formation of autoantibodies in patients. Myelin Oligodendrocyte Glycoprotein (MOG) has been studied previously as potential autoantigen in MS, which lead to the discovery of the MS autoantibody detecting peptide CSF114(N-Glc). This N-glycosylated peptide was able to successfully detect and characterize antibodies in MS patients. The specific posttranslational modification of the CSF114(N-Glc) peptide is virtually absent in eukaryotes, however can be found in abundance in prokaryotic cell surface proteins, thus making these glycoprotein conjugates candidate antigens in development of autoimmune diseases such as MS. Resulting from this reasoning, it has been found that anti-CSF114(N-Glc) antibodies of MS patients also recognize HMW1ct-Glc, an extracellular N-glycosylated adhesin fragment of H. influenzae.

However up until now, the native MS antigen has not been elucidated. Although the synthetic glycosylated peptides and proteins are able to act as probes for detection of antibodies in MS patients, therefore thought to mimic the native epitope, the real antigen presented in patients is as of yet unknown. Hence identification of the native antigen through the design of immunoprecipitation experiments is of utmost interest.

2. Identification and Characterization of Epitope Peptides for Detection of Anti-Adalimumab Antibodies in JIA-Patient Serum

Juvenile idiopathic arthritis (JIA) is an autoimmune disease. Polyarticular JIA affects 5 or more joints—often the same joints on both sides of the body. Sometimes the neck, jaw joints, and small joints in the hands and feet are affected. JIA is the most common type of autoimmune arthritis in children. It occurs more often in girls and can cause inflammation, swelling, stiffness, and pain in the joints, as well as other symptoms, depending on the type of juvenile idiopathic arthritis a child has. The project deals with the characterization of anti-drug antibodies (ADA) developed by some of the patients treated with the therapeutic antibody Adalimumab. Adalimumab is a TNF blocker medicine that can lower the ability of the immune system to fight infections. Nevertheless, it is accepted that anti-Adalimumab antibodies are frequently neutralizing, i.e. abolishing or dramatically diminishing the pharmacological efficacy of the drug. The analysis and characterisation of peptide epitopes (using Liquid-Chromatography Mass Spectrometry – LCMS) recognised by ADA circulating in patient serum, will allow the rational design of synthetic peptide epitopes as probes to be used in a simple ELISA enabling faster and easier screening of patients to help clinicians deciding on alternative treatments.

Publications:

  • Antibody Epitope of Human -GalactosidaseA Revealed by Affinity Mass Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement Therapy of Fabry Disease. Kukacka, Z.; Iurascu, M.; Lupu, L.; Rusche, H.; Murphy, M.; Altamore, L.; Borri, F.; Maeser, S.; Papini, A. M.; Hennermann, J.; Przybylski, M. ChemMedChem, 2018, 13, 909 –915.
  •  Cloning, functional expression and characterization of a bifunctional 3-hydroxybutanal dehydrogenase/reductase involved in acetone metabolism by Desulfococcus biacutus. Frey, J.; Rusche, H.; Schink, B.; Schleheck, D. BMC Microbiology, 2016, 16, 280.

 

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