Ciliopathies
Most ciliopathies are caused by mutations and present as syndromic disorders (i.e. Bardet-Biedl-, Alström-, Joubert Syndrome). Some ciliopathies are restricted to a single organ like certain forms of Leber congenital amaurosis (LCA), where patients suffer from blindness without being affected from other symptoms.
We aim at identifying the molecular mechanisms of ciliopathies looking into the endophenotype of the affected cells. To achieve this, we employ high end quantitative mass spectrometric approaches with the goal to identify changes in interconnectivity of proteins that ultimately lead to the disease phenotypes. This in combination with cell biology, analysis of signalling and high resolution imaging including STED and EM helps us to decipher how cilia integrate cellular functions from single cells to complex tissues and how these get lost with ciliary dysfunction.
Current Projects
- Impact of missense mutations in recessive Mendelian disease: Insight from ciliopathies. Wellcome Trust Collaborative Award in Science: (2019-2024)
- Neurodevelopmental ciliopathies: a multimodel approach from molecular mechanisms to patients variant interpretation and treatment strategies, NDCil, EU (2022-2026)
- European Training Network for Studying Ciliary Signalling In Development and Disease, SCiLS, EU (2020-2024)
- Multimodale Analyse der durch CRB1 Mutationen ausgelösten Netzhautdegeneration in humanen retinalen Organoiden aus Stammzellen. DFG (2019-2023)
- Analyse der molekularen Funktion von ALMS1. DFG (2022-2025)
- Analyse der molekularen Funktion von ALMS1. University of Tübingen ƒortüne-programme (2021-2022)
- Tistou and Charlotte Kerstan Foundation 2010-date
Collaborations
- Ronald Roepman, Radboud University Medical Center, Department of Human Genetics, Nijmegen, The Netherlands
- Rob Russell, Protein Evolution group, BioQuant and Biochemie Zentrum (BZH), University of Heidelberg
- Colin Johnson, Medical & Molecular Genetics, University of Leeds, UK
- Heymut Omran, Laboratory for cilia research, Westfälische Wilhelms-Universität (WWU) Münster, Germany
- Soren Christensen, Cell biology and Physiology, University of Copenhagen, Denmark
- Heiko Lickert, Institute of Diabetes and Regeneration Research, Helmholtz Diabetes Centerand Technical University Munich, Germany
- Achim Gossler, Institute of Molecular Biology, Medizinische Hochschule Hannover, Germany
- Robert Lukowski, Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, Germany
- Phil Beales and Dagan Jenkins, Genetics and Genomic Medicine, Cilia Disorders, UCL Great Ormond Street Institute of Child Health, London, UK
- Steve Twigg, Wilkie Group: Clinical Genetics, Weatherall Institute of Molecular Medicine, University of Oxford, UK
- Sylvie Schneider-Maunoury, Institut de Biologie Paris-Seine (IBPS), Université Pierre et Marie Curie, Paris, France
- Enza Maria Valente, Department of Molecular Medicine, University of Pavia, Italy
- Oliver Blacque, School of Biomolecular and Biomedical Science, University College Dublin, Ireland
- András Dr. Dinnyés, HCEMM-USZ StemCell Research Group, Szeged, Hungary
Selected Publications
- Szymanska K, Boldt K, Logan CV, Adams M, Robinson PA, Ueffing M, Zeqiraj E, Wheway G, and Johnson CA. Regulation of canonical Wnt signalling by the ciliopathy protein MKS1 and the E2 ubiquitin-conjugating enzyme UBE2E1. Elife. 2022;11(
- Volz AK, Frei A, Kretschmer V, de Jesus Domingues AM, Ketting RF, Ueffing M, Boldt K, Kramer-Albers EM, and May-Simera HL. Bardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles. Nature communications. 2021;12(1):5671.
- Beyer T, Klose F, Kuret A, Hoffmann F, Lukowski R, Ueffing M, and Boldt K. Tissue- and isoform-specific protein complex analysis with natively processed bait proteins. J Proteomics. 2021;231(103947.
- Latour BL, Van De Weghe JC, Rusterholz TD, Letteboer SJ, Gomez A, Shaheen R, Gesemann M, Karamzade A, Asadollahi M, Barroso-Gil M, Chitre M, Grout ME, van Reeuwijk J, van Beersum SE, Miller CV, Dempsey JC, Morsy H, University of Washington Center for Mendelian G, Bamshad MJ, Genomics England Research C, Nickerson DA, Neuhauss SC, Boldt K, Ueffing M, Keramatipour M, Sayer JA, Alkuraya FS, Bachmann-Gagescu R, Roepman R, and Doherty D. Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. J Clin Invest. 2020;130(8):4423-39.
- Kennedy SA, Jarboui MA, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn MA, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko BN, Iglesias-Martinez LF, Ryan CJ, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn DJ, and Kolch W. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). Nature communications. 2020;11(1):499.
- Ying G, Boldt K, Ueffing M, Gerstner CD, Frederick JM, and Baehr W. The small GTPase RAB28 is required for phagocytosis of cone outer segments by the murine retinal pigmented epithelium. J Biol Chem. 2018;293(45):17546-58.
- Beyer T, Bolz S, Junger K, Horn N, Moniruzzaman M, Wissinger Y, Ueffing M, and Boldt K. CRISPR/Cas9-mediated Genomic Editing of Cluap1/IFT38 Reveals a New Role in Actin Arrangement. Mol Cell Proteomics. 2018;17(7):1285-94.
- Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, van Beersum SE, Horn N, Willer JR, Mans DA, Dougherty G, Lamers IJ, Coene KL, Arts HH, Betts MJ, Beyer T, Bolat E, Gloeckner CJ, Haidari K, Hetterschijt L, Iaconis D, Jenkins D, Klose F, Knapp B, Latour B, Letteboer SJ, Marcelis CL, Mitic D, Morleo M, Oud MM, Riemersma M, Rix S, Terhal PA, Toedt G, van Dam TJ, de Vrieze E, Wissinger Y, Wu KM, Apic G, Beales PL, Blacque OE, Gibson TJ, Huynen MA, Katsanis N, Kremer H, Omran H, van Wijk E, Wolfrum U, Kepes F, Davis EE, Franco B, Giles RH, Ueffing M, Russell RB, Roepman R, and Group UKRD. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications. 2016;7(11491.
- Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TT, Racher H, Phelps IG, Toedt G, Kennedy J, Wunderlich KA, Sorusch N, Abdelhamed ZA, Natarajan S, Herridge W, van Reeuwijk J, Horn N, Boldt K, Parry DA, Letteboer SJF, Roosing S, Adams M, Bell SM, Bond J, Higgins J, Morrison EE, Tomlinson DC, Slaats GG, van Dam TJP, Huang L, Kessler K, Giessl A, Logan CV, Boyle EA, Shendure J, Anazi S, Aldahmesh M, Al Hazzaa S, Hegele RA, Ober C, Frosk P, Mhanni AA, Chodirker BN, Chudley AE, Lamont R, Bernier FP, Beaulieu CL, Gordon P, Pon RT, Donahue C, Barkovich AJ, Wolf L, Toomes C, Thiel CT, Boycott KM, McKibbin M, Inglehearn CF, Consortium UK, University of Washington Center for Mendelian G, Stewart F, Omran H, Huynen MA, Sergouniotis PI, Alkuraya FS, Parboosingh JS, Innes AM, Willoughby CE, Giles RH, Webster AR, Ueffing M, Blacque O, Gleeson JG, Wolfrum U, Beales PL, Gibson T, Doherty D, Mitchison HM, Roepman R, and Johnson CA. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nat Cell Biol. 2015;17(8):1074-87.
- Boldt K, Mans DA, Won J, van Reeuwijk J, Vogt A, Kinkl N, Letteboer SJ, Hicks WL, Hurd RE, Naggert JK, Texier Y, den Hollander AI, Koenekoop RK, Bennett J, Cremers FP, Gloeckner CJ, Nishina PM, Roepman R, and Ueffing M. Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice. J Clin Invest. 2011;121(6):2169-80.