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Uniklinik Köln

Congenital connective tissue disorders, fibrillinopathies

German

Our workgroup is part of the Department of Pediatrics and Adolescent Medicine at the Medical Faculty of the University of Cologne. Our laboratory is situated at the Center for Biochemistry.

The main focus of our research is to understand the underlying disease mechanisms of pediatric connective tissue disorders, such as cutis laxa, systemic sclerosis, dysregulated bone growth, muscle dystrophy, or the formation of early aortic aneurysms. Our aim is to understand how the extracellular matrix (ECM) regulates the bioavailability of growth factors such as BMPs and TGF-β. This implicates to investigate the pathomechanisms triggered by structural deficiencies in the ECM architecture which are often accompanied by growth factor dysregulation.

We actively participate in the Collaborative Research Centre 829 "Molecular mechanisms regulating skin homeostasis", in the DFG Research Unit FOR2722 "Novel molecular determinants for musculoskeletal extracellular matrix homeostasis - a systemic approach" , as well as in the newly established Collaborative Research Centre TRR259 "Aortic diseases". In addition, we are associated to the Center for Molecular Medicine Cologne (CMMC).

Prof. Dr.--Sengle-Gerhard
Prof. Dr. Gerhard Sengle

Leader of Research Group Congenital connective tissue disorders, fibrillinopathies

telephone icon +49 221 478-97260

Projects

The Team

Christin Adamo, PhD student
Annkatrin Correns, PhD student
Dr. Katrin Hildebrandt, postdoc
Steffen Lütke, PhD student
Yousef Morcos, PhD student
Gabriel Hella, student lab assistant
Dr. Dagmar Sonntag-Bensch, animal models TRR259/ S01
Chara Spanou, PhD student
Antje Tenbieg, Technician
Laura-Marie Zimmermann, PhD student

Publications of the last five years

Original publications

  1. Hiepen C, Jatzlau J, Hildebrandt S, Kampfrath B, Goktas M, Murgai A, Cuellar Camacho JL, Haag R, Ruppert C, Sengle G, Cavalcanti-Adam EA, Blank KG, Knaus P (2019). BMPR2 acts as a gatekeeper to protect endothelial cells from increased TGFβ responses and altered cell mechanics. PLoS Biol. 17: e3000557.
  2. Mayorca-Guiliani AE, Willacy O, Madsen CD, Rafaeva M, Elisabeth Heumüller S, Bock F, Sengle G, Koch M, Imhof T, Zaucke F, Wagener R, Sasaki T, Erler JT, Reuten R (2019). Decellularization and antibody staining of mouse tissues to map native extracellular matrix structures in 3D. Nat Protoc. 14: 3395-3425.
  3. Heumüller SE, Talantikite M, Napoli M, Armengaud J, Mörgelin M, Hartmann U, Sengle G, Paulsson M, Moali C, Wagener R (2019). C-terminal proteolysis of the collagen VI α3 chain by BMP-1 and proprotein convertase(s) releases endotrophin in fragments of different sizes. J Biol Chem. 294: 13769-13780.
  4. Elezagic D, Mörgelin M, Hermes G, Hamprecht A, Sengle G, Lau D, Höllriegl S, Wagener R, Paulsson M, Streichert T, Klatt AR (2019). Antimicrobial peptides derived from the cartilage.-specific C-type Lectin Domain Family 3 Member A (CLEC3A) - potential in the prevention and treatment of septic arthritis. Osteoarthritis Cartilage 27: 1564-1573.
  5. Yin W, Kim HT, Wang S, Gunawan F, Li R, Buettner C, Grohmann B, Sengle G, Sinner D, Offermanns S, Stainier DYR. Fibrillin-2 is a key mediator of smooth muscle extracellular matrix homeostasis during mouse tracheal tubulogenesis. Eur Respir J. (2019) 53(3).
  6. Lockhart-Cairns MP, Lim KTW, Zuk A, Godwin ARF, Cain SA, Sengle G, Baldock C (2019). Internal cleavage and synergy with twisted gastrulation enhance BMP inhibition by BMPER. Matrix Biol. (2019) 77, 73-86.
  7. Mularczyk EJ, Singh M, Godwin ARF, Galli F, Humphreys N, Adamson AD, Mironov A, Cain SA, Sengle G, Boot-Handford RP, Cossu G, Kielty CM, Baldock C (2018). ADAMTS10-mediated tissue disruption in Weill-Marchesani Syndrome. Hum Mol Genet. 27, 3675-3687.
  8. Ruthard J, Hermes G, Hartmann U, Sengle G, Pongratz G, Ostendorf B, Schneider M, Höllriegl S, Zaucke F, Wagener R, Streichert T, Klatt AR (2018). Identification of antibodies against extracellular matrix proteins in human osteoarthritis. Biochem Biophys Res Commun. 503, 1273-1277.
  9. Do NN, Willenborg S, Eckes B, Jüngst C, Sengle G, Zaucke F, Eming SA (2018). Myeloid Cell-Restricted STAT3 Signaling Controls a Cell-Autonomous Antifibrotic Repair Program. J Immunol. 201, 663-674.
  10. Nüchel J, Ghatak S, Zuk AV, Illerhaus A, Mörgelin M, Schönborn K, Blumbach K, Wickström SA, Krieg T, Sengle G, Plomann M, Eckes B (2018). TGFB1 is secreted through an unconventional pathway dependent on the autophagic machinery and cytoskeletal regulators. Autophagy 14, 465-486.
  11. Vallecillo-García P, Orgeur M, Vom Hofe-Schneider S, Stumm J, Kappert V, Ibrahim DM, Börno ST, Hayashi S, Relaix F, Hildebrandt K, SengleG, Koch M, Timmermann B, Marazzi G, Sassoon DA, Duprez D, Stricker S (2017). Odd skipped-related 1 identifies a population of embryonic fibro-adipogenic progenitors regulating myogenesis during limb development. Nat Commun. 8, 1218.
  12. Schiavinato A, Keene DR, Imhof T, Doliana R, Sasaki T, Sengle G (2017). Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of osteoblasts. Sci Rep. 7, 5526.
  13. Brauchle E, Bauer H, Fernes P, Zuk A, Schenke-Layland K, Sengle G (2017). Raman microspectroscopy as a diagnostic tool for the non-invasive analysis of fibrillin-1 deficiency in the skin and in the in vitro skin models. Acta Biomater. 52, 41-48.
  14. Corallo D, Schiavinato A, Bizzotto D, Milanetto M, Guljelmovic M, Keene DR, Sengle G, Braghetta P, Bonaldo P. EMILIN3, an extracellular matrix molecule with restricted distribution in skin. Exp Dermatol. (2017) 26, 435-438.
  15. Gkogkolou P, Hildebrandt K, Broekaert S, Metze D, Sengle G*, Böhm M*. Cutis laxa acquisita: novel insights into impaired elastic fibre regeneration. Br J Dermatol. (2017) 176, 832-835. *Shared senior authors.
  16. Bultmann-Mellin I, Essers J, van Heijingen P, von Melchner H, Sengle G, Anja Sterner Kock A (2016). Function of Ltbp 4L and fibulin 4 in survival and elastogenesis. Dis Model Mech. 9, 1367-1374.
  17. Troilo H, Barrett AL, Zuk AV, Lockhart-Cairns MP, Wohl AP, Bayley CP, Dajani R, Tunnicliffe RB, Green L, Jowitt TA, Sengle G, Baldock C (2016). Structural characterization of twisted gastrulation provides insights into opposing functions on the BMP signalling pathway. Matrix Biol. 55, 49-62.
  18. Wohl AP, Troilo H, Zuk AV, Collins R, Baldock C, Sengle G (2016). Extracellular regulation of BMP activity by the microfibril component fibrillin-1. J Biol Chem. 291, 12732-46.
  19. Schiavinato A, Keene DR, Wohl AP, Corallo D, Colombatti A, Wagener R, Paulsson M, Bonaldo P, Sengle G (2016). Targeting of EMILIN-1 and EMILIN-2 to fibrillin microfibrils facilitates their incorporation into the extracellular matrix. J Invest Dermatol. (2016) 136, 1150-1160.
  20. Pilecki B, Holm AT, Schlosser A, Moeller JB, Wohl AP, Zuk AV, Heumüller SE, Wallis R, Moestrup SK, Sengle G, Holmskov U, Sorensen GL (2016). Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation. J Biol Chem. 291, 1103-14.
  21. Sengle G, Carlberg V, Tufa SF, Charbonneau NL, Smaldone S, Carlson EJ, Ramirez F, Keene DR, Sakai LY (2015). Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice. PLoS Genet. 11, e1005340.
  22. Bultmann-Mellin I, Conradi A, Maul AC, Dinger K, Wempe F, Wohl AP, Imhof T, Wunderlich FT,  Bunck AC, Nakamura T, Koli K, Bloch W, Ghanem A, Heinz A, von Melchner H, Sengle G, Sterner-Kock A (2015). Modeling autosomal recessive cutis laxa type 1C (ARCL1C) in mice reveals distinct functions of Ltbp-4 isoforms. Dis Model Mech. 8, 403-15.

Reviews

  1. Zimmermann LM, Mehrkens D, Baldus S, Sengle G (2020). Vaskuläre Inflammation: Interaktion zwischen ECM und Immunzellen. Trillium Immunologie 4(1) im Druck.
  2. Zigrino P, and Sengle G (2019). Fibrillin microfibrils and proteases, key integrators of fibrotic pathways. Adv Drug Deliv Rev. 146:3-16.
  3. Schulz JN, Plomann M, Sengle G, Gullberg D, Krieg T, Eckes B (2018). New developments on skin fibrosis - Essential signals emanating from the extracellular matrix for the control of myofibroblasts. Matrix Biol. 68-69:522-532.
  4. Troilo H, Barrett AL, Wohl AP, Jowitt TA, Collins RF, Bayley CP, Zuk AV, Sengle G, Baldock C. The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity. Biochem Soc Trans. (2015) 43, 795-800.
  5. Sengle G, Sakai LY. The fibrillin microfibril scaffold: A niche for growth factors and mechanosensation? Matrix Biol. (2015) 47, 3-12.