Experimental research in the Department of Pediatrics

University Children's Research (UCR)

  • About Us
  • About Us

    UCR@Kinder-UKE houses the pediatric academic research laboratories of the UKE. It is a research hub deeply intertwined with the Pediatric University Center for Innovative Therapies (ped.UCiT). Our department is dedicated to investigating rare genetic diseases, particularly those affecting the pediatric population. Our core goal is to understand the molecular mechanisms underlying these conditions. We study protein misfolding in inborn errors of metabolism and the dynamics of macromolecular protein complexes, delving into the fundamental processes driving pathology and aiming at drug development. Our department hosts a diverse array of expertise ranging from biochemical and biophysical assays to computational modeling and network medicine. Through collaborative partnerships and interdisciplinary innovation, we strive to accelerate the translation of scientific discoveries into benefits to patients.

    We prioritize the development of personalized medicine protocols, leveraging population studies and advanced genetic analyses to tailor therapies to individual patients. Guided by patient insights from our children´s hospital, our research is driven by scientific curiosity and the urgent clinical need for effective treatments to improve outcomes and enhance the quality of life of our children.

  • Kontaktbild Prof. Dr. med. Søren W. Gersting

    Prof. Dr. med

    Søren W. Gersting


    gersting@uke.de

    Søren W. Gersting, MD, is a Professor and Head of University Children’s Research at the Kinder-UKE. He earned his MD from Ludwig-Maximilians-University in Munich in 2002, where he focused on gene therapy for cystic fibrosis. He then completed his postdoctoral training at Dr. von Hauner Children’s Hospital in Munich.

    In 2018, Dr. Gersting was appointed Professor of Pediatric Research at the University Medical Center Hamburg-Eppendorf (UKE). His research investigates how genetic variations lead to altered protein function, particularly through protein misfolding. Dr. Gersting’s work aims to translate these mechanistic insights into novel treatment strategies for rare genetic diseases.

    His translational research incorporates systems medicine, machine learning, and AI-powered approaches to unravel the complex processes underlying these diseases. By identifying and targeting promising compounds, his team is pioneering new therapeutic avenues, including the development of pharmacological chaperones to provide effective solutions for patients suffering from rare genetic conditions.

Research Groups

UCRdrugdev

  • About us
  • About us

    UCRdrugdev is dedicated to rare genetic disease research, driven by the urgent clinical need for effective treatments. These diseases, often characterized by missense mutations resulting in protein misfolding and loss-of-function, encompass various inborn errors of metabolism (IEM). Current therapies, primarily dietary restrictions and stress management, often fall short in improving patient outcomes or quality of life. With a comprehensive understanding of molecular mechanisms and a robust drug development pipeline, we focus on developing pharmacological chaperones to stabilize aberrant proteins. We prioritize input from patients at our children's hospital, guiding our selection of target proteins for investigation. Utilizing our drug screening platform, we identify initial hits, which undergo thorough validation and optimization cycles using specialized biochemical and biophysical assays. Moreover, we expedite discovery by leveraging our cross-disease knowledge and implementing drug repositioning, ultimately speeding up both the development of treatments and, most importantly, their availability for patients in need.

  • Pharmacological chaperones for the rescue of misfolded GCDH in Glutaric Aciduria Type 1

    Project PI: Dr. Madalena Barroso m.barroso@uke.de

     

    Identification of pharmacological chaperones for the therapy of the protein misfolding disorders: phenylketonuria

    Project PI: Prof. Dr. Søren Gersting gersting@uke.de

     

    Identification of pharmacological chaperones for the therapy of the protein misfolding disorders: medium chain acyl-coA dehydrogenase deficiency

    Project PI: Dr. Nora Constanze Laubach n.laubach@uke.de

     

    Identification of allosteric pharmacological chaperones for the therapy of the protein misfolding disorders: Glutaric Aciduria Type 1

    Project PI: Dr. Madalena Barroso m.barroso@uke.de

    Collaborators: Gain Therapeutics, Switzerland

     

    Pharmacological chaperone screening for severe and frequent PKU patient variants

    Project PI: Prof. Dr. Søren Gersting gersting@uke.de

    Collaborators: iniuva GmbH, Germany

    Funding: iniuva GmbH, Germany

     

    Investigation of flavin adenine dinucleotide (FAD) as a pharmacological chaperone for acyl-CoA-dehydrogenases (ACADs)

    Project PI: Prof. Dr. Søren Gersting gersting@uke.de

     

    Synthesis and Assessment of Lead Compounds as Potential Pharmacological Chaperones for Glutaric Aciduria Type 1

    Project PI: Prof. Dr. Søren Gersting gersting@uke.de

    • High throughput screening
    • Cell-culture disease models
    • Recombinant protein expression and purification (FPLC)
    • Enzymatic assays
    • Thermal shift assay
    • Dynamic light scattering
    • Multi-angle light scattering
    • Aggregation assays
    • Isothermal titration calorimetry

  • A comprehensive comparison of deep learning-based compound-target interaction prediction models to unveil guiding design principles.
    Abdollahi S, Schaub D P, Barroso M, Laubach N C, Hutwelker W, Panzer U, Gersting SW, Bonn S.
    J CHEMIFORMATICS. 2024; 16(118). doi: 10.1186/s13321-024-00913-1

    Use of the Novel Site-Directed Enzyme Enhancement Therapy (SEE-Tx) Drug Discovery Platform to Identify Pharmacological Chaperones for Glutaric Acidemia Type 1
    Barroso M,     Puchwein-Schwepcke A, Buettner L, Goebel I, Küchler K, Muntau AC, Delgado A, Garcia-Collazo AM, Martinell M, Barril X, Cubero E, Gersting SW.
    J MED CHEM. 2024; 67, 19:17087-17100. doi: 10.1021/acs.jmedchem.4c00292

    Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1
    Barroso M, Gertzen M, Puchwein-Schwepcke AF, Preisler H, Sturm A, Reiss DD, Danecka MK, Muntau AC, Gersting SW.
    Int J Mol Sci. 2023 Aug 24;24(17):13158. doi: 10.3390/ijms241713158.

    The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.
    Gonzalez Melo M, Remacle N, Cudré-Cung HP, Roux C, Poms M, Cudalbu C, Barroso M, Gersting SW, Feichtinger RG, Mayr JA, Costanzo M, Caterino M, Ruoppolo M, Rüfenacht V, Häberle J, Braissant O, Ballhausen D.
    Mol Genet Metab. 2021 Jun;133(2):157-181. doi: 10.1016/j.ymgme.2021.03.017. Epub 2021 Apr 18.

    Disease-causing mutations affecting surface residues of mitochondrial glutaryl-CoA dehydrogenase impair stability, heteromeric complex formation and mitochondria architecture.
    Schmiesing J, Lohmöller B, Schweizer M, Tidow H, Gersting SW, Muntau AC, Braulke T, Mühlhausen C.
    Hum Mol Genet. 2017 Feb 1;26(3):538-551. doi: 10.1093/hmg/ddw411.

    The domain-specific and temperature-dependent protein misfolding phenotype of variant medium-chain acyl-CoA dehydrogenase.
    Jank JM, Maier EM, Reiβ DD, Haslbeck M, Kemter KF, Truger MS, Sommerhoff CP, Ferdinandusse S, Wanders RJ, Gersting SW, Muntau AC.
    PLoS One. 2014 Apr 9;9(4):e93852. doi: 10.1371/journal.pone.0093852. eCollection 2014.

    Innovative strategies to treat protein misfolding in inborn errors of metabolism: pharmacological chaperones and proteostasis regulators.
    Muntau AC, Leandro J, Staudigl M, Mayer F, Gersting SW.
    J Inherit Metab Dis. 2014 Jul;37(4):505-23. doi: 10.1007/s10545-014-9701-z. Epub 2014 Apr 1.

    Novel pharmacological chaperones that correct phenylketonuria in mice.
    Santos-Sierra S, Kirchmair J, Perna AM, Reiss D, Kemter K, Röschinger W, Glossmann H, Gersting SW, Muntau AC, Wolber G, Lagler FB.
    Hum Mol Genet. 2012 Apr 15;21(8):1877-87. doi: 10.1093/hmg/dds001. Epub 2012 Jan 13.

    Bioluminescence resonance energy transfer: an emerging tool for the detection of protein-protein interaction in living cells.
    Gersting SW, Lotz-Havla AS, Muntau AC.
    Methods Mol Biol. 2012;815:253-63. doi: 10.1007/978-1-61779-424-7_19.
    PMID: 22130997

    The interplay between genotype, metabolic state and cofactor treatment governs phenylalanine hydroxylase function and drug response.
    Staudigl M, Gersting SW, Danecka MK, Messing DD, Woidy M, Pinkas D, Kemter KF, Blau N, Muntau AC.
    Hum Mol Genet. 2011 Jul 1;20(13):2628-41. doi: 10.1093/hmg/ddr165. Epub 2011 Apr 28.

    Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism.
    Muntau AC, Gersting SW.
    J Inherit Metab Dis. 2010 Dec;33(6):649-58. doi: 10.1007/s10545-010-9185-4. Epub 2010 Sep 8.

    New insights into tetrahydrobiopterin pharmacodynamics from Pah enu1/2, a mouse model for compound heterozygous tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.
    Lagler FB, Gersting SW, Zsifkovits C, Steinbacher A, Eichinger A, Danecka MK, Staudigl M, Fingerhut R, Glossmann H, Muntau AC.
    Biochem Pharmacol. 2010 Nov 15;80(10):1563-71. doi: 10.1016/j.bcp.2010.07.042. Epub 2010 Aug 10.

    Activation of phenylalanine hydroxylase induces positive cooperativity toward the natural cofactor.
    Gersting SW, Staudigl M, Truger MS, Messing DD, Danecka MK, Sommerhoff CP, Kemter KF, Muntau AC.
    J Biol Chem. 2010 Oct 1;285(40):30686-97. doi: 10.1074/jbc.M110.124016. Epub 2010 Jul 27.

    Pahenu1 is a mouse model for tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency and promotes analysis of the pharmacological chaperone mechanism in vivo.
    Gersting SW, Lagler FB, Eichinger A, Kemter KF, Danecka MK, Messing DD, Staudigl M, Domdey KA, Zsifkovits C, Fingerhut R, Glossmann H, Roscher AA, Muntau AC.
    Hum Mol Genet. 2010 May 15;19(10):2039-49. doi: 10.1093/hmg/ddq085. Epub 2010 Feb 23.

    Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening.
    Maier EM, Gersting SW, Kemter KF, Jank JM, Reindl M, Messing DD, Truger MS, Sommerhoff CP, Muntau AC.
    Hum Mol Genet. 2009 May 1;18(9):1612-23. doi: 10.1093/hmg/ddp079. Epub 2009 Feb 18.

    Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability.
    Gersting SW, Kemter KF, Staudigl M, Messing DD, Danecka MK, Lagler FB, Sommerhoff CP, Roscher AA, Muntau AC.
    Am J Hum Genet. 2008 Jul;83(1):5-17. doi: 10.1016/j.ajhg.2008.05.013. Epub 2008 Jun 5.

UCRmetab

  • About us
  • About us

    UCRmetab, part of UCR@Kinder-UKE, delves into the mechanistic basis of rare genetic diseases, particularly focusing on protein misfolding, a common mechanism in inherited metabolic disorders such as phenylketonuria, MCAD deficiency, and glutaric acidemia. Using patient cell and protein-based models, we deepen our understanding of disease and aim to identify new or more effective biomarkers. Our translational efforts encompass systems medicine approaches targeting the phenylalanine hydroxylase proteostasis network and exploring the impact of genetic variants in metabolic disorders. Leveraging enzymatic assays and specialized expertise in missense mutation-induced protein misfolding, we actively promote drug development tailored to rare genetic diseases, striving for more therapeutic options and personalized treatment approaches to better serve our unique patient populations.

  • Characterization of phenylalanine hydroxylase proteostasis network

    Project PI: Dr. Madalena Barroso m.barroso@uke.de

     

    Characterization of misfolded protein variants in rare genetic diseases

    Project PI: Dr. Madalena Barroso m.barroso@uke.de

     

    Establishment of a GCDH activity assay for monitoring of activity in animal tissues

    Project PI: Dr. Madalena Barroso m.barroso@uke.de

    Funding: Dr. Diana Ballhausen - University of Lausanne and University Hospital of Lausanne, Switzerland

     

    Understanding brain-specific GCDH-linked metabolism

    Project PI: Dr. Madalena Barroso m.barroso@uke.de

    Funding: Prof. Dr. Ronald Wanders - Amsterdam University Medical Center, Nederlands

     

    Interaction network of CLPB variants

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

    • Cell-culture disease models
    • BRET (Bioluminescence Resonance Energy Transfer) Assays
    • Enzymatic assays
    • Recombinant protein expression and purification (FPLC)
    • Thermal shift assay
    • Aggregation assays
    • Blotting and immuno assays

  • Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1.
    Barroso M, Gertzen M, Puchwein-Schwepcke AF, Preisler H, Sturm A, Reiss DD, Danecka MK, Muntau AC, Gersting SW.
    Int J Mol Sci. 2023 Aug 24;24(17):13158. doi: 10.3390/ijms241713158.

    The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.
    Gonzalez Melo M, Remacle N, Cudré-Cung HP, Roux C, Poms M, Cudalbu C, Barroso M, Gersting SW, Feichtinger RG, Mayr JA, Costanzo M, Caterino M, Ruoppolo M, Rüfenacht V, Häberle J, Braissant O, Ballhausen D.
    Mol Genet Metab. 2021 Jun;133(2):157-181. doi: 10.1016/j.ymgme.2021.03.017. Epub 2021 Apr 18.

    Disease-causing mutations affecting surface residues of mitochondrial glutaryl-CoA dehydrogenase impair stability, heteromeric complex formation and mitochondria architecture.
    Schmiesing J, Lohmöller B, Schweizer M, Tidow H, Gersting SW, Muntau AC, Braulke T, Mühlhausen C.
    Hum Mol Genet. 2017 Feb 1;26(3):538-551. doi: 10.1093/hmg/ddw411.

    The domain-specific and temperature-dependent protein misfolding phenotype of variant medium-chain acyl-CoA dehydrogenase.
    Jank JM, Maier EM, Reiβ DD, Haslbeck M, Kemter KF, Truger MS, Sommerhoff CP, Ferdinandusse S, Wanders RJ, Gersting SW, Muntau AC.
    PLoS One. 2014 Apr 9;9(4):e93852. doi: 10.1371/journal.pone.0093852. eCollection 2014.

    Bioluminescence resonance energy transfer: an emerging tool for the detection of protein-protein interaction in living cells.
    Gersting SW, Lotz-Havla AS, Muntau AC.
    Methods Mol Biol. 2012;815:253-63. doi: 10.1007/978-1-61779-424-7_19.
    PMID: 22130997

    The interplay between genotype, metabolic state and cofactor treatment governs phenylalanine hydroxylase function and drug response.
    Staudigl M, Gersting SW, Danecka MK, Messing DD, Woidy M, Pinkas D, Kemter KF, Blau N, Muntau AC.
    Hum Mol Genet. 2011 Jul 1;20(13):2628-41. doi: 10.1093/hmg/ddr165. Epub 2011 Apr 28.

    Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening.
    Maier EM, Gersting SW, Kemter KF, Jank JM, Reindl M, Messing DD, Truger MS, Sommerhoff CP, Muntau AC.
    Hum Mol Genet. 2009 May 1;18(9):1612-23. doi: 10.1093/hmg/ddp079. Epub 2009 Feb 18.

    Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability.
    Gersting SW, Kemter KF, Staudigl M, Messing DD, Danecka MK, Lagler FB, Sommerhoff CP, Roscher AA, Muntau AC.
    Am J Hum Genet. 2008 Jul;83(1):5-17. doi: 10.1016/j.ajhg.2008.05.013. Epub 2008 Jun 5.

UCRcomplex

  • About us
  • About us

    Proteins rarely act as single entities. To function properly, the majority of proteins interact with other proteins, forming macromolecular protein complexes. Our main interest is to better understand metabolic disorders by investigating protein complexes in disease conditions. Using complexome profiling as our main research tool, we gain insight into the composition, stability, assembly/disassembly and dynamics of macromolecular protein complexes. Complexome profiling is a technique used in molecular biology to study protein complexes within cells. It involves the separation and analysis of native protein complexes under physiological conditions, providing insights into the organization of these complexes within a cellular context. The process typically involves separation of proteins without disrupting their native interactions by techniques such as blue-native PAGE or clear native PAGE followed by mass spectrometry analysis to identify and quantify the individual proteins within the complexes.

  • Multiplexed complexomics to foster routine protein complex profiling in medical research and diagnostics

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

    Collaborators: Prof. Hartmut Schlüter

    Funding: Else-Kröner-Fresenius Stiftung (2019_A135)

     

    Complexome remodeling and lysine acylation in organic acidemias

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

    Collaborators: Mathias Woidy, Klinik und Poliklinik für Kinder- und Jugendmedizin, Kinder-UKE / Zina Piper Maastricht University

     

    Medium chain acyl-CoA dehydrogenase in-gel activity assay development.

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

    Collaborators: Prof. Charlotte Uetrecht, Centre for Structural Systems Biology, Hamburg, Germany

     

    Analysis of lung tissue from CFTR knockout mice with cystic fibrosis by complexome profiling.

    Project PI: Prof. Michaela Schedel

    Collaborators: Prof. Michaela Schedel, Translational Pulmonology, Ruhrlandklinik, Universitätsmedizin Essen, Essen, Germany

     

    Characterization of oxidative phosphorylation complexes during oocyte to embryo transition.

    Project PI: Prof. Ruth Lehmann

    Collaborators: Dr. Christoph Gaebelein/Prof. Ruth Lehmann, Whitehead Institute, Massachusetts Institute of Technology, Cambridge, USA

     

    Complexome analysis of patient fibroblast with suspected mitochondriopathies.

    Project PI: Dr. Kostantinos Tsiakas tsiakas@uke.de

    Collaborators: Dr. Konstantinos Tsiakas / Dr. Mathias Woidy, Klinik und Poliklinik für Kinder- und Jugendmedizin, Kinder-UKE

     

    Functional analysis of UQCC4 on the assembly of multi-subunit protein complexes in mitochondria.

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

    Collaborators: Prof. Ilka Wittig / Dr. Alfredo Cabrera-Orefice, Goethe Universität, Frankfurt am Main, Germany

     

    Mitochondrial proteome remodeling and compensatory mechanisms in glutaric acidemia type I.

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

    Collaborators: Zina Piper, Maastricht University / Dr. Mathias Woidy

     

    Regulation of Inflammasomes Activation by Inter-organelle Protein Complexes.

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

     

    Interaction network of CLPB variants

    Project PI: Dr. Sergio Guerrero-Castillo s.guerrerocastillo@uke.de

    • Complexome Profiiling
    • Blue-native electrophoresis
    • hrCN-PAGE
    • In-vitro activity assays
    • In-gel activity assays
    • Cell culture and cell fractionation
    • Organelle enrichment

  • Multiplexed complexome profiling using tandem mass tags.
    Guerrero-Castillo S    , Krisp C, Küchler K, Arnold S, Schlüter H, Gersting SW. Biochim Biophys Acta Bioenerg. (2021) 1862(9):148448. doi: 10.1016/j.bbabio.2021.148448.

    Ablation of mitochondrial DNA results in widespread remodeling of the mitochondrial complexome.
    Guerrero-Castillo S,     van Strien J, Brandt U, Arnold S. EMBO J. (2021) e108648 doi: 10.15252/embj.2021108648.

    Complexome Profiling-Exploring Mitochondrial Protein Complexes in Health and Disease
    Cabrera-Orefice A, Potter A, Evers F, Hevler JF, Guerrero-Castillo S
    FRONT CELL DEV BIOL. 2021;9:796128. doi: 10.3389/fcell.2021.796128.

    Neutropenia and intellectual disability are hallmarks of biallelic and de novo CLPB
    deficiency
    Wortmann SB, Ziętkiewicz S, Guerrero-Castillo S, Feichtinger RG, Wagner M, Russell J,
    Ellaway C, Mróz D, Wyszkowski H, Weis D, Hannibal I, von Stülpnagel C, Cabrera-Orefice A,
    Lichter-Konecki U, Gaesser J, Windreich R, Myers KC, Lorsbach R, Dale RC, Gersting SW, Prada
    CE, Christodoulou J, Wolf NI, Venselaar H, Mayr JA, Wevers RA
    GENET MED. 2021;23(9):1705-1714. doi: 10.1038/s41436-021-01194-x.

    CEDAR, an online resource for the reporting and exploration of complexome profiling
    data
    van Strien J, Haupt A, Schulte U, Braun HP, Cabrera-Orefice A, Choudhary JS, Evers F,
    Fernandez-Vizarra E, Guerrero-Castillo S, Kooij TWA, Páleníková P, Pardo M, Ugalde C, Wittig
    I, Wöhlbrand L, Brandt U, Arnold S, Huynen MA
    BIOCHIM BIOPHYS ACTA BIOENERG. 2021;1862(7):148411. doi:
    10.1016/j.bbabio.2021.148411.

    The plastid proteome of the nonphotosynthetic chlorophycean alga Polytomella parva
    Fuentes-Ramírez EO, Vázquez-Acevedo M, Cabrera-Orefice A, Guerrero-Castillo S, González-
    Halphen D
    NICROBIOL RES. 2021;243:126649. doi: 10.1016/j.micres.2020.126649.

    TMEM70 functions in the assembly of complexes I and V
    Sánchez-Caballero L, Elurbe DM, Baertling F, Guerrero-Castillo S, van den Brand M, van Strien
    J, van Dam TJP, Rodenburg R, Brandt U, Huynen MA, Nijtmans LGJ
    BIOCHIM BIOPHYS ACTA BIOENERG. 2020;1861(8):148202. doi:
    10.1016/j.bbabio.2020.148202.

    Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-
    enzyme interface is associated with metabolic cutis laxa
    Mohamed M, Gardeitchik T, Balasubramaniam S, Guerrero-Castillo S, Dalloyaux D, van Kraaij
    S, Venselaar H, Hoischen A, Urban Z, Brandt U, Al-Shawi R, Simons JP, Frison M, Ngu LH,
    Callewaert B, Spelbrink H, Kallemeijn WW, Aerts JMFG, Waugh MG, Morava E, Wevers RA
    J INHERIT METAB DIS. 2020;43(6):1382-1391. doi: 10.1002/jimd.12255.

    COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein
    complexes in Barth syndrome
    Van Strien J, Guerrero-Castillo S, Chatzispyrou IA, Houtkooper RH, Brandt U, Huynen MA
    BIOINFORMATICS. 2019;35(17):3083-3091. doi: 10.1093/bioinformatics/btz025.

    Deactivation of mitochondrial complex I after hypoxia-ischemia in the immature brain
    Stepanova A, Konrad C, Guerrero-Castillo S, Manfredi G, Vannucci S, Arnold S, Galkin A
    J CEREB BLOOD FLOW METAB. 2019;39(9):1790-1802. doi: 10.1177/0271678X18770331.

    Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural
    Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies
    Gardeitchik T, Mohamed M, Ruzzenente B, Karall D, Guerrero-Castillo S, Dalloyaux D, van den
    Brand M, van Kraaij S, van Asbeck E, Assouline Z, Rio M, de Lonlay P, Scholl-Buergi S,
    Wolthuis DFGJ, Hoischen A, Rodenburg RJ, Sperl W, Urban Z, Brandt U, Mayr JA, Wong S, de
    Brouwer APM, Nijtmans L, Munnich A, Rötig A, Wevers RA, Metodiev MD, Morava E.
    AM J HUM GENET. 2018;102(4):685-695 doi: 10.1016/j.ajhg.2018.02.012.

    Barth syndrome cells display widespread remodeling of mitochondrial complexes
    without affecting metabolic flux distribution
    Chatzispyrou IA, Guerrero-Castillo S, Held N, Ruiter J, Denis S, Ijlst L, Wanders R, Weeghel M,
    Ferdinandusse S, Vaz F, Brandt U, Houtkooper RH
    BIOCHIM BIOPHYS ACTA MOL BASIS DIS. 2018;1864(11):3650-3658 doi:
    10.1016/j.bbadis.2018.08.041.

    The Assembly Pathway of Mitochondrial Respiratory Chain Complex I
    Guerrero-Castillo S, Baertling F, Kownatzki D, Wessels HJ, Arnold S, Brandt U, Nijtmans L
    CELL METAB. 2017;25(1):128-139 doi: 10.1016/j.cmet.2016.09.002.

    Identification and evolutionary analysis of tissue-specific isoforms of mitochondrial
    complex I subunit NDUFV3
    Guerrero-Castillo S, Cabrera-Orefice A, Huynen MA, Arnold S
    BIOCHIM BIOPHYS ACTA. 2017;1858(3):208-217 doi: 10.1016/j.bbabio.2016.12.004.

    MR-1S Interacts with PET100 and PET117 in Module-Based Assembly of Human
    Cytochrome c Oxidase
    Vidoni S, Harbour ME, Guerrero-Castillo S, Signes A, Ding S, Fearnley IM, Taylor RW, Tiranti
    V, Arnold S, Fernandez-Vizarra E, Zeviani M
    CELL REP. 2017;18(7):1727-1738 doi: 10.1016/j.celrep.2017.01.044.

    Mutations in ATP6V1E1 or ATP6V1A Cause Autosomal-Recessive Cutis Laxa
    Van Damme T, Gardeitchik T, Mohamed M, Guerrero-Castillo S, Freisinger P, Guillemyn B,
    Kariminejad A, Dalloyaux D, van Kraaij S, Lefeber DJ, Syx D, Steyaert W, De Rycke R,
    Hoischen A, Kamsteeg EJ, Wong SY, van Scherpenzeel M, Jamali P, Brandt U, Nijtmans L,
    Korenke GC, Chung BH, Mak CC, Hausser I, Kornak U, Fischer-Zirnsak B, Strom TM, Meitinger
    T, Alanay Y, Utine GE, Leung PK, Ghaderi-Sohi S, Coucke P, Symoens S, De Paepe A, Thiel
    C, Haack TB, Malfait F, Morava E, Callewaert B, Wevers RA
    AM J HUM GENET. 2017;100(2):216-227 doi: 10.1016/j.ajhg.2016.12.010.

    A homozygous missense mutation in ERAL1, encoding a mitochondrial rRNA chaperone,
    causes Perrault syndrome
    Chatzispyrou IA, Alders M, Guerrero-Castillo S, Zapata Perez R, Haagmans MA, Mouchiroud L,
    Koster J, Ofman R, Baas F, Waterham HR, Spelbrink JN, Auwerx J, Mannens MM, Houtkooper
    RH, Plomp AS
    HUM MOL GENET. 2017;26(13):2541-2550. doi: 10.1093/hmg/ddx152.

    The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in
    Mitochondria
    König T, Tröder SE, Bakka K, Korwitz A, Richter-Dennerlein R, Lampe PA, Patron M,
    Mühlmeister M, Guerrero-Castillo S, Brandt U, Decker T, Lauria I, Paggio A, Rizzuto R, Rugarli
    EI, De Stefani D, Langer T
    MOL CELL. 2016;64(1):148-162. doi: 10.1016/j.molcel.2016.08.020.

    Mutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and
    Isolated Complex I Deficiency
    Sánchez-Caballero L, Ruzzenente B, Bianchi L, Assouline Z, Barcia G, Metodiev MD, Rio M,
    Funalot B, van den Brand MA, Guerrero-Castillo S, Molenaar JP, Koolen D, Brandt U,
    Rodenburg RJ, Nijtmans LG, Rötig A
    AM J HUM GENET. 2016;99(1):208-16. doi: 10.1016/j.ajhg.2016.05.022.

    Unraveling the complexity of mitochondrial complex I assembly: A dynamic process
    Sánchez-Caballero L, Guerrero-Castillo S, Nijtmans L
    BIOCHIM BIOPHYS ACTA. 2016;1857(7):980-90. doi: 10.1016/j.bbabio.2016.03.031.

    Evolution and structural organization of the mitochondrial contact site (MICOS) complex
    and the mitochondrial intermembrane space bridging (MIB) complex
    Huynen MA, Mühlmeister M, Gotthardt K, Guerrero-Castillo S, Brandt U
    BIOCHIM BIOPHYS ACTA. 2016;1863(1):91-101. doi: 10.1016/j.bbamcr.2015.10.009.

UCRpersmed

  • About us
  • About us

    UCRpersmed is a dedicated research group specializing in personalized medicine protocols, with a focus on phenylketonuria (PKU). Through extensive population studies and advanced genetic analysis, we aim to uncover the prevalence and distribution of PAH gene variants globally. Employing innovative laboratory techniques, they delve into the functional properties of these variants, aiming to elucidate genotype-phenotype correlations crucial for individualized treatment strategies. UCRpersmed is committed to developing practical diagnostic tools and treatment algorithms, integrating molecular diagnostics and computational modeling to tailor therapies to each patient's unique genetic and metabolic profile. With collaborative partnerships driving knowledge exchange and interdisciplinary innovation, UCRpersmed strives to contribute to improved outcomes and quality of life for patients worldwide.

  • Researchers

    Student research assistants

    • Greta Stoltmann
    • Sahba Bahrani

    Alumni and Former Members

    • Malcolm Summer Rose-Heine
    • Viviane Kasten
    • Dr. Marta Danecka
    • Ingrid Goebel

  • Mechanisms of phenylalanine hydroxylase function

    Project PI: Dr. Polina Gundorova p.gundorova@uke.de

    Collaborators: Prof. Stefan Bonn, Dr. Behnam Yousefi, Robin Khatri - Center for Molecular Neurobiology Hamburg (ZMNH) Systembiology

     

    Database of PAH genotypes and PAH activity landscapes
    http://pah-activitylandscapes.org/

    Project PI: Dr. Polina Gundorova p.gundorova@uke.de

     

    Functional analysis for PAH intronic variants

    Project PI: Dr. Polina Gundorova p.gundorova@uke.de

    Collaborators: Rachael McNeilly, Rebecca Whittington, Ian Berry - Bristol Genetics Laboratory, North Bristol NHS Trust, Bristol, England, United Kingdom

    Funding: 2025 - 2028: DFG grant GU 2431/2-1 "Functional studies using a personalized approach to treat phenylketonuria patients"

     

    Personalized treatment for phenylketonuria patients

    Project PI: Dr. Polina Gundorova p.gundorova@uke.de

    Collaborators:

    • Dr. Maja Stojiljkovic, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
    • Dr. Lucia Sur, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj, Romania
    • Dr. Romana Vulturar, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj, Romania
    • Dr. Daniela Iorgulescu, Department of Pediatrics, National Institute for Mother and Child Health "Alessandrescu-Rusescu", Bucharest, Romania
    • Prof. Dr. Urh Groselj, University of Ljubljana, Faculty of Medicine, University Children's Hospital Ljubljana, Ljubljana, Slovenia
    • Prof. Dr. Jeongho Lee, Department of Pediatrics, Soonchunhyang University Hospital, Seoul, Korea
    • Prof. Dr. Ida Vanessa Schwartz, Dr. Rafael Hencke Tresbach, PhD, Genetics Department, Hospital de Clinicas de Porto Alegre-UFRGS, Porto Alegre, Brazil
    • Dr. Ana Chiesa, Buenos Aires Childrens Hospital, Buenos Aires, Argentina

    Funding: 2022: Biomarin research grant; 2025 - 2028: DFG grant GU 2431/2-1 "Functional studies using a personalized approach to treat phenylketonuria patients"

     

    PAH activity landscapes for 50 frequent Russian mild genotypes

    Project PI: Dr. Polina Gundorova p.gundorova@uke.de

    Funding: 2020: DAAD short-term research fellowship
    2021-2023: Humboldt Research Fellowship for Postdoctoral Researchers

    • Cell culture disease models
    • Protein activity assays
    • Automated liquid handling
    • High performance liquid chromatography (HPLC)

  • BH4-deficient hyperphenylalaninemia in Russia
    Gundorova P, Kuznetcova IA, Baydakova GV, Stepanova AA, Itkis YS, Kakaulina VS,
    Alferova IP, Lyazina LV, Andreeva LP, Kanivets I, Zakharova EY, Kutsev SI, Polyakov
    AV
    PLoS ONE. 2021;16(4):e0249608. doi:10.1371/journal.pone.0249608

    The Genetic Landscape and Epidemiology of Phenylketonuria
    Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, Chiesa AE,
    Christodoulou J, Đorđević M, Desviat LR, Eliyahu A, Evers RAF, Fajkusova L, Feillet F, Bonfim-
    Freitas PE, Giżewska M, Gundorova P, Karall D, Kneller K, Kutsev SI, Leuzzi V, Levy HL,
    Lichter-Konecki U, Muntau AC, Namour F, Oltarzewski M, Paras A, Perez B, Polak E, Polyakov
    AV, Porta F, Rohrbach M, Scholl-Bürgi S, Spécola N, Stojiljković M, Shen N, Santana-da Silva
    LC, Skouma A, van Spronsen F, Stoppioni V, Thöny B, Trefz FK, Vockley J, Yu Y, Zschocke J,
    Hoffmann GF, Garbade SF, Blau N
    AM J HUM GENET. 2020;107(2). doi: 10.1016/j.ajhg.2020.06.006

    Genotypes of 2579 patients with phenylketonuria reveal a high rate of BH4 non-
    responders in Russia
    Gundorova P, Stepanova AA, Kuznetsova IA, Kutsev SI, Polyakov AV
    PLoS ONE. 2019;14(1):e0211048. doi:10.1371/journal.pone.0211048

    The study of the full spectrum of variants leading to hyperphenylalaninemia have
    revealed 10 new variants in the PAH gene
    Kuznetcova I, Gundorova P, Ryzhkova O, Polyakov A
    METAB BRAIN DIS. 2019;34(6):1547-1555. doi: 10.1007/s11011-019-00461-w

    Molecular-genetic causes for the high frequency of phenylketonuria in the population
    from the North Caucasus
    Gundorova P, Zinchenko RA, Kuznetsova IA, Bliznetz EA, Stepanova AA, Polyakov AV
    PLoS ONE. 2018;13(8):e0201489. doi:10.1371/journal.pone.0201489

    Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH)
    genotypes promotes personalised medicine in phenylketonuria
    Danecka MK, Woidy M, Zschocke J, Feillet F, Muntau AC, Gersting SW
    J MED GENET. 2015;52(3):175-85. doi: 10.1136/jmedgenet-2014-102621

    The interplay between genotype, metabolic state and cofactor treatment governs
    phenylalanine hydroxylase function and drug response
    Staudigl M, Gersting SW, Danecka MK, Messing DD, Woidy M, Pinkas D, Kemter KF, Blau N,
    Muntau AC
    HUM MOL GENET. 2011;20(13):2628-41. doi: 10.1093/hmg/ddr165.

UCRnetmed

  • About us
  • About us

    Coming from basic and applied science in the field of mathematics and physics, network medicine has a holistic approach to analyze and represent biological systems. Cellular components such as DNA, RNA, proteins, and metabolites interact with each other and are collectively condensed in huge biological network. Diseases are seen as local perturbations caused within these networks. The tools provided by network medicine enable the in-silico study of diseases and their related perturbations at molecular level, the investigation of their mechanistic links to other diseases and the repurposing of therapeutic approaches from one disease to a neighboring disease. We recently demonstrated the applicability of such methods to the group of Inborn Errors of Metabolism (IEM) and focus our work on the understanding of IEM. In more detail, we want to leverage the potential of network medicine as a cheap tool to create opportunities for drug repurposing and finally help our patients.

  • Researchers

    Alumni and Former Members

    • Zina Piper (Master thesis: A network medicine approach identifies DLD, MDH and SDH as potential therapeutic targets in Organic Acidemias)

  • Applying network based approaches to study inborn errors of metabolism

    Project PI: Dr. med. Dipl.-Ing.(FH) Mathias Woidy m.woidy@uke.de , Dr. med. Julia Cramer j.cramer@uke.de

     

    Drug-repurposing for inborn errors of metabolism.

    Project PI: Dr. med. Dipl.-Ing.(FH) Mathias Woidy m.woidy@uke.de

    Collaborators: Prof. Dr. Harald H.H.W. Schmidt, MD PhD PharmD (Maastrich University)

     

    Etablierung einer VR-Platform in der klinischen Routine.

    Project PI: Dr.med. Dipl.-Ing.(FH) Mathias Woidy m.woidy@uke.de

    Collaborators: Univ.-Prof. Dr. rer. nat. Dipl.-Phys. Jörg Menche (Vienna)

     

    Identification of the PAH proteostasis network.

    Project PI: Dr. med. Dipl.-Ing.(FH) Mathias Woidy m.woidy@uke.de , Dr.med. Julia Cramer j.cramer@uke.de

    Collaborators: Luka Haupt, Dr. Madalena Barroso

    • BRET-based protein-interaction screening
    • In-Silico modelling of molecular networks: Python and R

  • Further information will be provided soon.

UCRneuro

  • About us
  • About us

    UCRneuro analyzes CLN7 disease, a lysosomal neurodegenerative storage disorder belonging to the group of neuronal ceroid lipofuscinoses (NCLs), which is caused by the loss of the lysosomal membrane protein CLN7. We have generated mouse models for CLN7 which recapitulate key features of human CLN7 disease like neurodegeneration, neuroinflammation and lysosomal dysfunction. We analyse CLN7 patient mutations and their impact on half life times, intracellular trafficking and localization, N-glycosylation and proteolytic cleavage of CLN7 to identify mutations with functional impairment. Linkages in biochemical functions and common neurodegenerative pathways using Cln7-deficient mouse models and cell lines are explored. Biochemical methods are utilized to identify the unknown function/substrates of CLN7 in lysosomes. Aim of our studies is to identify main pathomechanisms of CLN7 disease leading to lysosomal dysfunction and neurodegeneration, possible biochemical and pathomechanical linkages with other NCLs and the unknown function/substrates of the putative lysosomal membrane transporter CLN7.

  • Researchers

    PD Dr. Stephan Storch storch@uke.de ORCID

    Master students

    Liana Uebler

    Student research assistants

    Berker Ersoy

    Alumni and Former Members

    Dr. rer. nat. Tatyana Danyukova (Post-Doc)
    Dr. med. Khandsuren Ariunbat (Doktoral student)
    Sneha Nemani (M. Sc.)
    Dr. rer. nat. Laura Brandenstein (Doktoral student)
    Dr. rer. nat. Mine Franke (Doktoral student, DFG-Graduate College 1459)
    Dr. rer. nat. Pieter Steenhuis (Doktorand, DFG-Graduate College 1459)
    Dr. med. Jana Galal (Doktoral student)
    Dr. med. Adrian Meder (Doktoral student)

  • Functional analysis of CLN7 and identification of pathomechanisms in CLN7 disease

    Project PI: PD Dr. Stephan Storch storch@uke.de

    Collaborators: Dr. Christian Posern, Dr. Angela Schulz

    Funding: 2019-2024 : Mila’s Miracle Foundation, Bolder, USA

    • Mouse models for CLN7 disease
    • CLN7-deficient cell lines (MEFs, HAP1 cells, cerebellar cell lines)
    • Biochemical and cell biological analysis of lysosomal and autophagic dysfunction
    • Sorting and trafficking motifs of lysosomal membrane proteins
    • Subcellular fractionation
    • Double immunofluorescence microscopy
    • Isolation of lysosomes using magnetobeads and antibody-based methods (Lyso-IP)
    • Stable isotope labeling with amino acids in cell culture (SILAC)
    • Proteomic analyses of lysosomes
    • Analysis of genotype- phenotype correlations in CLN7 disease

  • CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry
    Heinl ES, Lorenz S, Schmidt B, Nasser M Laqtom N, Mazzulli JR, Francelle L, Yu TW,
    Greenberg B, Storch S, Tegtmeier I, Othmen H, Maurer K, Steinfurth M, Witzgall R, Milenkovic
    V, Wetzel CH, Reichold M
    iSCIENCE. 2022;25:105082. doi: 10.1016/j.isci.2022.105082.

    CLN7 mutation causes aberrant redistribution of protein isoforms and contributes to
    Batten disease pathobiology
    Sharaireh AM, Guevara-Ferrer M, Herranz-Martin S, Garcia-Macia M, Phillips A, Tierney A,
    Hughes MP, Coombe-Tennant O, Nelvagel H, Burrows AE, Fielding S, FitzPatrick LM, Thornton
    CD, Storch S, Mole SE, Dowsey A, Unwin R, Bolanos JP, Rahim AA, McKay TR
    BioRxiv. 2022. doi: 10.1101 /2022.04.21.488782

    Experimental therapeutic approaches for the treatment of retinal pathology in neuronal
    ceroid lipofuscinoses
    Bartsch U, Storch S.
    FRONT NEUROL. 2022;13:866983. doi: 10.3389/fneur.2022.866983.

    Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid
    lipofuscinosis
    Lopez-Fabuel I, Garcia-Macia M, Buondelmonte C, Burmistrova O, Bonora N, Alonso-Batan P,
    Morant-Ferrando B, Vicente-Gutierrez C, Jimenez-Blasco D, Quintana-Cabrera R, Fernandez E,
    Llop J, Ramos-Cabrer P, Sharaireh A, Guevara-Ferrer M, Fitzpatrick L, Thompton CD, McKay
    TR, Storch S, Medina DL, Mole SE, Fedichev PO, Almeida A, Bolaños JP
    NAT COMMUN. 2022;13:536. doi: 10.1038/s41467-022-28191-1.

    Converging roles of PSENEN/PEN2 and CLN3 in the autophagy-lysosome system
    Klein M, Kaleem A, Oetjen S, Wünkhaus D, Binkle L, Schilling S, Gjorgjieva M, Scholz R,
    Gruber-Schoffnegger D, Storch S, Kins S, Drewes G, Hoffmeister-Ullerich S, Kuhl D, Hermey G
    AUTOPHAGY. 2021;29:1-18. doi: 10.1080/15548627.2021.2016232

    Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype
    Soldati C, Lopez-Fabuel I, Wanderlingh LG, Garcia-Macia M, Monfregola J, Esposito A,
    Napolitano G, Guevara-Ferrer M, Scotto Rosato A, Krogsaeter EK, Paquet D, Grimm CM,
    Montefusco S, Braulke T, Storch S, Mole SE, De Matteis MA, Ballabio A, Sampaio JL, McKay T,
    Johannes L, Bolanos JP, Medina DL
    EMBO MOL MED. 2021;13:e13742. doi: 10.15252/emmm.202013742.

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th
    edition)
    Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H,
    Abildgaard MH, Abudu YP et al.
    AUTOPHAGY. 2021;17:1-382. doi: 10.1080/15548627.2020.1797280.

    Modulation of Kv4.2/KChIP3 interaction by the ceroid lipofuscinosis neuronal 3 protein
    CLN3
    Seifert C, Storch S, Bähring R
    J BIOL CHEM. 2020;295:12099-12110. doi: 10.1074/jbc.RA120.013828.

    Functional characterization of novel MFSD8 pathogenic variants anticipates neurological
    involvement in juvenile isolated maculopathy
    Bauwens M, Storch S, Weisschuh N, Ceuterick-de Groote C, De Rycke R, Guillemyn B, De
    Jaegere S, Coppieters F, Van Cos-ter R, Leroy BP, De Baere E
    CLIN GENET. 2020;97:426-436. doi: 10.1111/cge.13673.

    A newly generated neuronal cell model of CLN7 disease reveals aberrant lysosome
    motility and impaired cell survival
    von Kleist L, Ariunbat K, Braren I, Stauber T, Storch S, Danyukova T
    MOL GENET METAB. 2019;126:196-205. doi: 10.1016/j.ymgme.2018.09.009.

    Current and emerging treatment strategies for neuronal ceroid lipofuscinoses
    Kohlschütter A, Schulz A, Bartsch U, Storch S
    CNS DRUGS. 2019;33:315-325. doi: 10.1007/s40263-019-00620-8.

    Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a
    complex retinal phenotype
    Atiskova Y, Bartsch S, Danyukova T, Becker E, Hagel C, Storch S, Bartsch U
    SCI REP. 2019;9:14185. doi: 10.1038/s41598-019-50726-8.

    The CLN3 gene and protein: What we know
    Mirza M, Vainshtein A, DiRonza A, Chandrachud U, Haslett LJ, Palmieri M, Storch S, Groh J,
    Dobzinski N, Napolitano G, Schmidtke C, Kerkovich DM
    MOL GENET GENOMIC MED. 2019;7(12):e859. doi: 10.1002/mgg3.859.

    Loss of CLN7 results in depletion of soluble lysosomal proteins and impaired mTOR
    reactivation
    Danyukova T, Ariunbat K, Thelen M, Brocke-Ahmadinejad N, Mole SE, Storch S
    HUM MOL GENET. 2018;27:1711-1722. doi: 10.1093/hmg/ddy076.

    Disease-linked glutarylation im-pairs function and interactions of mitochondrial proteins
    and contributes to mitochondrial heterogeneity
    Schmiesing J, Storch S, Dörfler AC, Schweizer M, Makrypidi-Fraune G, Thelen M, Sylvester M,
    Gieselmann V, Meyer-Schwesinger C, Koch-Nolte F, Tidow H, Mühlhausen C, Waheed A, Sly
    WS, Braulke T
    CELL REP. 2018;24:2946-2956. doi: 10.1016/j.celrep.2018.08.014.

    Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the
    lysosomal membrane protein Cln7
    Brandenstein L, Schweizer M, Sedlacik J, Fiehler J, Storch S
    HUM MOL GENET. 2016; 25:777-791. doi: 10.1093/hmg/ddv615.

    Retinal Degeneration in Mice Deficient in the Lysosomal Membrane Protein CLN7
    Jankowiak W, Brandenstein L, Dulz S, Hagel C, Storch S, Bartsch U
    INVEST OPHTALMOL VIS SCI. 2016;57:4989-4998. doi: 10.1167/iovs.16-20158.

    Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease
    Damme M, Brandenstein L, Fehr S, Jankowiak W, Bartsch U, Schweizer M, Hermans-
    Borgmeyer I, Storch S
    NEUROBIOL DIS. 2014;65:12-24. doi: 10.1016/j.nbd.2014.01.003.

    Transport of the GlcNAc-1-phosphotransferase α/β-subunit precursor protein to the
    Golgi apparatus requires a combinatorial sorting motif
    Franke M, Braulke T, Storch S
    J BIOL CHEM. 2013;288:1238–1249. doi: 10.1074/jbc.M112.407676.

    Proteolytic cleavage of the disease-related lysosomal membrane glycoprotein CLN7
    Steenhuis P, Froemming J, Reinheckel T, Storch S
    BIOCHIM BIOPHYS ACTA. 2012;1822:1617-1628. doi: 10.1016/j.bbadis.2012.05.015.

UCRµbiom

  • About us
  • About us

    Chronic inflammatory diseases present a major health burden among pediatric patients. The underlying pathomechanisms are based on a combination of genetic susceptibility, environmental triggers, intestinal dysbiosis, and immunometabolic dysregulation leading to sustained inflammation. Hence, reprogramming of the gut immune axis due to early life infections that require antibiotic treatment and hospitalization could be an environmental trigger favoring sustained inflammatory responses.
    1. Preterm neonates are susceptible to sepsis and show signs of chronic inflammatory dysregulation as seen in bronchopulmonary dysplasia (BPD). We study the gut immune axis in preterm neonates, by employing a multi-omics approach using stool and blood samples in patients with neonatal sepsis versus healthy controls. Thereby we identify risk categories that result in a personalized preventive medicine model to reduce the risk of chronic inflammatory diseases.
    2. We study a cohort of juvenile idiopathic arthritis (JIA) patients to gain a better understanding of the pediatric gut immune axis, once inflammation has become chronically dysregulated. We analyze clinical datasets as well as stool, blood and synovial fluid samples of JIA patients with a multiomics approach. In addition, we use a 3D model of the synovial membrane to study the interaction of immune cells and the synovial membrane, as well as to test new therapeutic approaches such as modulators of immune cell metabolism. Ultimately, we aim to improve the understanding of JIA pathogenesis and to provide biomarkers in the gut-immune-axis that enable individualized treatment of JIA patients.

  • Further information will be provided soon.

  • Further information will be provided soon.

UCRnephro

  • About us
  • About us

    UCRnephro is studying genetic kidney diseases with a focus on glomerular disease. This includes identification and characterization of novel monogenic causes of nephrotic syndrome (NS) and congenital anomalies of the kidney and urinary tract (CAKUT). Furthermore, a spectrum of glomerular disease with genetic predisposition leading to susceptibility towards environmental trigger factors is recognized. Under this hypothesis, we are aiming to use insight gained from rare monogenic diseases to develop treatment strategies for acquired glomerular diseases.

  • Further information will be provided soon.

    • Exome sequencing
    • Gene and gene-set burden analysis
    • scRNA transcriptomics
    • 2D and 3D (kidney organoids) Cell-culture disease models
    • Mouse disease models
    • Recombinant protein expression and purification
    • Immunofluorescence and laser scanning confocal microscopy
    • Flow cytometry
    • Luciferase assays
    • AAV-based gene replacement therapy

  • Further information will be provided soon.

Zertifikat Ausgezeichnet für Kinder
Gütesiegel der Deutschen Gesellschaft für Muskelkranke e.V.