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Experimental Neonatology

Experimentelle Neonatologie

Our research focusses on multifactorial aspects of development that contribute to children’s disorders. Various risk factors e.g. malnutrition, inflammation or prematurity could severely impair children’s life and we now want to unravel the underlying key mechanisms to understand how changes in development can result in children’s diseases. Most likely environmental changes during a critical window of development can induce long term modifications that impair children’s health. We hypothesize that these can cause epigenetic, proteomic and metabolic modifications to alter the communication of cells with the surrounding extracellular matrix (ECM), to impair tissue stability and function and finally to affect childrens health.

In our current research we want to understand how alterations in microRNAs, extracellular matrix proteins and mitochondria function affect cell-matrix interactions to destabilize organ development and function during fetal, neonatal and adolescent life. This research should contribute to the development of new diagnostic tools and therapeutic strategies for children’s disease.

Current Projects

  • Mitochondria dysfunction in the developing cartilage
  • Posttranscriptional regulation of tissue development, homeostasis and disease
  • ECM-Immune interactions
  • Annexins in health and disease

The Team

Univ. Prof. Dr. rer. nat. Bent Brachvogel, leader
Telefon +49 221 478-6996
E-Mail bent.brachvogel@uni-koeln.de

Markus Auler
Dr. rer. nat. Björn Bluhm
Dr. rer. nat. Julia Etich
Christian Frie
Veronika Georgieva
Kristina Probst
Mengjie Zhou

Publications

  1. Shimada A, Ideno H, Arai Y, Komatsu K, Wada S, Yamashita T, Amizuka N, Pöschl E, Brachvogel B, Nakamura Y, Nakashima K, Mizukami H, Ezura Y, Nifuji A. Annexin A5 involvement in bone overgrowth at the enthesis. J Bone Miner Res. 2018 Apr 25. ndoi: 10.1002/jbmr.3453. [Epub ahead of print] PubMed PMID: 29694681.

  2. Brylka LJ, Köppert S, Babler A, Kratz B, Denecke B, Yorgan TA, Etich J, Costa IG, Brachvogel B, Boor P, Schinke T, Jahnen-Dechent W. Post-weaning epiphysiolysis causes distal femur dysplasia and foreshortened hindlimbs in fetuin-A-deficient mice. PLoS One. 2017 Oct 31;12(10):e0187030. doi: 10.1371/journal.pone.0187030. eCollection 2017. PubMed PMID: 29088242; PubMed Central PMCID: PMC5663435.

  3. Weiland D, Brachvogel B, Hornig-Do HT, Neuhaus JFG, Holzer T, Tobin DJ, Niessen CM, Wiesner RJ, Baris OR. Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation. J Invest Dermatol. 2018 Jan;138(1):132-140. doi: 10.1016/j.jid.2017.08.019. Epub 2017 Sep 1. PubMed PMID: 28867657.

  4. Bluhm B, Ehlen HWA, Holzer T, Georgieva VS, Heilig J, Pitzler L, Etich J, Bortecen T, Frie C, Probst K, Niehoff A, Belluoccio D, Van den Bergen J, Brachvogel B. miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage. Development. 2017 Oct 1;144(19):3562-3577. doi: 10.1242/dev.148429. Epub 2017 Aug 29. PubMed PMID: 28851708.

  5. Leite Dantas R, Brachvogel B, Schied T, Bergmeier V, Skryabin B, Vogl T, Ludwig S, Wixler V. The LIM-Only Protein Four and a Half LIM Domain Protein 2 Attenuates Development of Psoriatic Arthritis by Blocking Adam17-Mediated Tumor Necrosis Factor Release. Am J Pathol. 2017 Nov;187(11):2388-2398. doi: 10.1016/j.ajpath.2017.07.015. Epub 2017 Aug 18. PubMed PMID: 28823868.

  6. Bergmeier V, Etich J, Pitzler L, Frie C, Koch M, Fischer M, Rappl G, Abken H, Tomasek JJ, Brachvogel B. Identification of a myofibroblast-specific expression signature in skin wounds. Matrix Biol. 2018 Jan;65:59-74. doi: 10.1016/j.matbio.2017.07.005. Epub 2017 Aug 7. PubMed PMID: 28797711.

  7. Leite Dantas R, Masemann D, Schied T, Bergmeier V, Vogl T, Loser K, Brachvogel B, Varga G, Ludwig S, Wixler V. Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes. J Pathol. 2016 Nov;240(3):366-377. doi: 10.1002/path.4786. PubMed PMID: 27555499.

  8. Etich J, Bergmeier V, Pitzler L, Brachvogel B. Identification of a reference gene for the quantification of mRNA and miRNA expression during skin wound healing. Connect Tissue Res. 2017 Mar;58(2):196-207. doi: 10.1080/03008207.2016.1210606. Epub 2016 Jul 7. PubMed PMID: 27386825.

  9. Scholz P, Auler M, Brachvogel B, Benzing T, Mallman P, Streichert T, Klatt AR. Detection of multiple annexin autoantibodies in a patient with recurrentn miscarriages, fulminant stroke and seronegative antiphospholipid syndrome. Biochem Med (Zagreb). 2016;26(2):272-8. doi: 10.11613/BM.2016.032. PubMed PMID: 27346975; PubMed Central PMCID: PMC4910275.

  10. Steiger J, Stephan A, Inkeles MS, Realegeno S, Bruns H, Kröll P, de Castro Kroner J, Sommer A, Batinica M, Pitzler L, Kalscheuer R, Hartmann P, Plum G, Stenger S, Pellegrini M, Brachvogel B, Modlin RL, Fabri M. Imatinib Triggers Phagolysosome Acidification and Antimicrobial Activity against Mycobacterium bovis Bacille Calmette-Guérin in Glucocorticoid-Treated Human Macrophages. J Immunol. 2016 Jul 1;197(1):222-32. doi: 10.4049/jimmunol.1502407. Epub 2016 May 27. PubMed PMID: 27233968; PubMed Central PMCID: PMC5536119.

  11. Kreft S, Klatt AR, Straßburger J, Pöschl E, Flower RJ, Eming S, Reutelingsperger C, Brisson A, Brachvogel B. Skin Wound Repair Is Not Altered in the Absence of Endogenous AnxA1 or AnxA5, but Pharmacological Concentrations of AnxA4 and AnxA5 Inhibit Wound Hemostasis. Cells Tissues Organs. 2016;201(4):287-98. doi: 10.1159/000445106. Epub 2016 Apr 30. PubMed PMID: 27178140.

  12. Zhou Z, Pausch F, Schlötzer-Schrehardt U, Brachvogel B, Pöschl E. Erratum to: Induction of initial steps of angiogenic differentiation and maturation of endothelial cells by pericytes in vitro and the role of collagen IV. Histochem Cell Biol. 2016 May;145(5):527-9. doi: 10.1007/s00418-016-1429-4. PubMed PMID: 27038636.

  13. Reuten R, Nikodemus D, Oliveira MB, Patel TR, Brachvogel B, Breloy I, Stetefeld J, Koch M. Maltose-Binding Protein (MBP), a Secretion-Enhancing Tag for Mammalian Protein Expression Systems. PLoS One. 2016 Mar 30;11(3):e0152386. doi: 10.1371/journal.pone.0152386. eCollection 2016. PubMed PMID: 27029048; PubMed Central PMCID: PMC4814134.

  14. Pitzler L, Auler M, Probst K, Frie C, Bergmeier V, Holzer T, Belluoccio D, van den Bergen J, Etich J, Ehlen H, Zhou Z, Bielke W, Pöschl E, Paulsson M, Brachvogel B. miR-126-3p Promotes Matrix-Dependent Perivascular Cell Attachment, Migration and Intercellular Interaction. Stem Cells. 2016 May;34(5):1297-309.doi: 10.1002/stem.2308. Epub 2016 Mar 9. Erratum in: Stem Cells. 2017 Jul;35(7):1866. PubMed PMID: 26934179.

  15. Zhou Z, Pausch F, Schlötzer-Schrehardt U, Brachvogel B, Pöschl E. Induction of initial steps of angiogenic differentiation and maturation of endothelial cells by pericytes in vitro and the role of collagen IV. Histochem Cell Biol. 2016 May;145(5):511-25. doi: 10.1007/s00418-015-1398-z. Epub 2016 Jan 9. Erratum in: Histochem Cell Biol. 2016 May;145(5):527-9. PubMed PMID: 26747274.

  16. Etich J, Brachvogel B. [Role of cartilage extracellular matrix for the development and function of the immune system]. Z Rheumatol. 2015 Oct;74(8):711-3. doi: 10.1007/s00393-015-1650-x. German. PubMed PMID: 26450435.

  17. Etich J, Holzer T, Pitzler L, Bluhm B, Brachvogel B. MiR-26a modulates extracellular matrix homeostasis in cartilage. Matrix Biol. 2015 Apr;43:27-34. doi: 10.1016/j.matbio.2015.02.014. Epub 2015 Mar 10. PubMed PMID: 25766405.

  18. Brachs S, Turqueti-Neves A, Stein M, Reimer D, Brachvogel B, Bösl M, Winkler T, Voehringer D, Jäck HM, Mielenz D. Swiprosin-1/EFhd2 limits germinal center responses and humoral type 2 immunity. Eur J Immunol. 2014 Nov;44(11):3206-19. doi: 10.1002/eji.201444479. Epub 2014 Sep 16. PubMed PMID: 25092375.

  19. Brachvogel B, Zaucke F, Dave K, Norris EL, Stermann J, Dayakli M, Koch M, Gorman JJ, Bateman JF, Wilson R. Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome. J Biol Chem. 2013 May 10;288(19):13481-92. doi: 10.1074/jbc.M112.444810. Epub 2013 Mar 24. PubMed PMID: 23530037; PubMed Central PMCID: PMC3650385.

  20. Etich J, Bergmeier V, Frie C, Kreft S, Bengestrate L, Eming S, Mauch C, Eckes B, Ulus H, Lund FE, Rappl G, Abken H, Paulsson M, Brachvogel B. PECAM1(+)/Sca1(+)/CD38(+) vascular cells transform into myofibroblast-like cells in skin wound repair. PLoS One. 2013;8(1):e53262. doi: 10.1371/journal.pone.0053262. Epub 2013 Jan 4. PubMed PMID: 23308177; PubMed Central PMCID: PMC3537615.

  21. Ueki H, Mizushina T, Laoharatchatathanin T, Terashima R, Nishimura Y, Rieanrakwong D, Yonezawa T, Kurusu S, Hasegawa Y, Brachvogel B, Pöschl E, Kawaminami M. Loss of maternal annexin A5 increases the likelihood of placental platelet thrombosis and foetal loss. Sci Rep. 2012;2:827. doi: 10.1038/srep00827. Epub 2012 Nov 9. PubMed PMID: 23145320; PubMed Central PMCID: PMC3494014.

  22. Ehlen HW, Chinenkova M, Moser M, Munter HM, Krause Y, Gross S, Brachvogel B, Wuelling M, Kornak U, Vortkamp A. Inactivation of anoctamin-6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues. J Bone Miner Res. 2013 Feb;28(2):246-59. doi: 10.1002/jbmr.1751. PubMed PMID: 22936354.

  23. Grskovic I, Kutsch A, Frie C, Groma G, Stermann J, Schlötzer-Schrehardt U, Niehoff A, Moss SE, Rosenbaum S, Pöschl E, Chmielewski M, Rappl G, Abken H, Bateman JF, Cheah KS, Paulsson M, Brachvogel B. Depletion of annexin A5, annexin A6, and collagen X causes no gross changes in matrix vesicle-mediated mineralization, but lack of collagen X affects hematopoiesis and the Th1/Th2 response. J Bone Miner Res. 2012 Nov;27(11):2399-412. doi: 10.1002/jbmr.1682. PubMed PMID: 22692895.

  24. Willenborg S, Lucas T, van Loo G, Knipper JA, Krieg T, Haase I, Brachvogel B, Hammerschmidt M, Nagy A, Ferrara N, Pasparakis M, Eming SA. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair. Blood. 2012 Jul 19;120(3):613-25. doi: 10.1182/blood-2012-01-403386. Epub 2012 May 10. PubMed PMID: 22577176.

  25. Groma G, Xin W, Grskovic I, Niehoff A, Brachvogel B, Paulsson M, Zaucke F. Abnormal bone quality in cartilage oligomeric matrix protein and matrilin 3 double-deficient mice caused by increased tissue inhibitor of metalloproteinases 3 deposition and delayed aggrecan degradation. Arthritis Rheum. 2012 Aug;64(8):2644-54. doi: 10.1002/art.34435. PubMed PMID: 22378539.

  26. Wilson R, Norris EL, Brachvogel B, Angelucci C, Zivkovic S, Gordon L, Bernardo BC, Stermann J, Sekiguchi K, Gorman JJ, Bateman JF. Changes in the chondrocyte and extracellular matrix proteome during post-natal mouse cartilage development. Mol Cell Proteomics. 2012 Jan;11(1):M111.014159. doi: 10.1074/mcp.M111.014159. Epub 2011 Oct 11. PubMed PMID: 21989018; PubMed Central PMCID: PMC3270109.

  27. Groma G, Grskovic I, Schael S, Ehlen HW, Wagener R, Fosang A, Aszodi A, Paulsson M, Brachvogel B, Zaucke F. Matrilin-4 is processed by ADAMTS-5 in late Golgi vesicles present in growth plate chondrocytes of defined differentiation state. Matrix Biol. 2011 May;30(4):275-80. doi: 10.1016/j.matbio.2011.04.002. Epub 2011 Apr 22. PubMed PMID: 21539915.

  28. Bouter A, Gounou C, Bérat R, Tan S, Gallois B, Granier T, d'Estaintot BL, Pöschl E, Brachvogel B, Brisson AR. Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair. Nat Commun. 2011;2:270. doi: 10.1038/ncomms1270. PubMed PMID: 21468022; PubMed Central PMCID: PMC3104517.

  29. Rosenbaum S, Kreft S, Etich J, Frie C, Stermann J, Grskovic I, Frey B, Mielenz D, Pöschl E, Gaipl U, Paulsson M, Brachvogel B. Identification of novel binding partners (annexins) for the cell death signal phosphatidylserine and definition of their recognition motif. J Biol Chem. 2011 Feb 18;286(7):5708-16. doi: 10.1074/jbc.M110.193086. Epub 2010 Dec 3. PubMed PMID: 21131363; PubMed Central PMCID: PMC3037683.

  30. Eming SA, Koch M, Krieger A, Brachvogel B, Kreft S, Bruckner-Tuderman L, Krieg T, Shannon JD, Fox JW. Differential proteomic analysis distinguishes tissue repair biomarker signatures in wound exudates obtained from normal healing and chronic wounds. J Proteome Res. 2010 Sep 3;9(9):4758-66. doi: 10.1021/pr100456d.PubMed PMID: 20666496.

  31. Belluoccio D, Etich J, Rosenbaum S, Frie C, Grskovic I, Stermann J, Ehlen H, Vogel S, Zaucke F, von der Mark K, Bateman JF, Brachvogel B. Sorting of growth plate chondrocytes allows the isolation and characterization of cells of a defined differentiation status. J Bone Miner Res. 2010 Jun;25(6):1267-81. doi:10.1002/jbmr.30. PubMed PMID: 20200945.

  32. Belluoccio D, Grskovic I, Niehoff A, Schlötzer-Schrehardt U, Rosenbaum S, Etich J, Frie C, Pausch F, Moss SE, Pöschl E, Bateman JF, Brachvogel B. Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of growth plate cartilage but does not inhibit the induction of mineralization. J Bone Miner Res. 2010 Jan;25(1):141-53. doi: 10.1359/jbmr.090710. PubMed PMID: 19580468.

  33. Allen JM, Zamurs L, Brachvogel B, Schlötzer-Schrehardt U, Hansen U, Lamandé SR, Rowley L, Fitzgerald J, Bateman JF. Mice lacking the extracellular matrix protein WARP develop normally but have compromised peripheral nerve structure and function. J Biol Chem. 2009 May 1;284(18):12020-30. doi: 10.1074/jbc.M806968200. Epub 2009 Mar 11. PubMed PMID: 19279005; PubMed Central PMCID: PMC2673271.

  34. Cameron TL, Belluoccio D, Farlie PG, Brachvogel B, Bateman JF. Global comparative transcriptome analysis of cartilage formation in vivo. BMC Dev Biol. 2009 Mar 10;9:20. doi: 10.1186/1471-213X-9-20. PubMed PMID: 19272164; PubMed Central PMCID: PMC2662817.

  35. Frey B, Munoz LE, Pausch F, Sieber R, Franz S, Brachvogel B, Poschl E, Schneider H, Rödel F, Sauer R, Fietkau R, Herrmann M, Gaipl US. The immune reaction against allogeneic necrotic cells is reduced in Annexin A5 knock out mice whose macrophages display an anti-inflammatory phenotype. J Cell Mol Med. 2009 Jul;13(7):1391-9. doi: 10.1111/j.1582-4934.2008.00395.x. Epub 2008 Jul 9. PubMed PMID: 18624762; PubMed Central PMCID: PMC4496152.

  36. Allen JM, Brachvogel B, Farlie PG, Fitzgerald J, Bateman JF. The extracellular matrix protein WARP is a novel component of a distinct subset of basement membranes. Matrix Biol. 2008 May;27(4):295-305. doi: 10.1016/j.matbio.2008.01.005. Epub 2008 Jan 30. PubMed PMID: 18314316.

  37. Mittag J, Oehr W, Heuer H, Hämäläinen T, Brachvogel B, Pöschl E, Bauer K. Expression and thyroid hormone regulation of annexins in the anterior pituitary. J Endocrinol. 2007 Dec;195(3):385-92. PubMed PMID: 18000301.

  38. Eming SA, Brachvogel B, Odorisio T, Koch M. Regulation of angiogenesis: wound healing as a model. Prog Histochem Cytochem. 2007;42(3):115-70. Epub 2007 Aug 20. Review. PubMed PMID: 17980716.

  39. Brachvogel B, Pausch F, Farlie P, Gaipl U, Etich J, Zhou Z, Cameron T, von der Mark K, Bateman JF, Pöschl E. Isolated Anxa5+/Sca-1+ perivascular cells from mouse meningeal vasculature retain their perivascular phenotype in vitro and in vivo. Exp Cell Res. 2007 Jul 15;313(12):2730-43. Epub 2007 May 8. PubMed PMID: 17543301.

  40. Gaipl US, Munoz LE, Rödel F, Pausch F, Frey B, Brachvogel B, von der Mark K, Pöschl E. Modulation of the immune system by dying cells and the phosphatidylserine-ligand annexin A5. Autoimmunity. 2007 Jun;40(4):254-9. Review. PubMed PMID: 17516206.

  41. Munoz LE, Frey B, Pausch F, Baum W, Mueller RB, Brachvogel B, Poschl E, Rödel F, von der Mark K, Herrmann M, Gaipl US. The role of annexin A5 in the modulation of the immune response against dying and dead cells. Curr Med Chem. 2007;14(3):271-7. Review. PubMed PMID: 17305532.

  42. Munoz LE, Franz S, Pausch F, Fürnrohr B, Sheriff A, Vogt B, Kern PM, Baum W, Stach C, von Laer D, Brachvogel B, Poschl E, Herrmann M, Gaipl US. The influence on the immunomodulatory effects of dying and dead cells of Annexin V. J Leukoc Biol. 2007 Jan;81(1):6-14. Epub 2006 Sep 27. PubMed PMID: 17005907.

  43. Brachvogel B, Moch H, Pausch F, Schlötzer-Schrehardt U, Hofmann C, Hallmann R, von der Mark K, Winkler T, Pöschl E. Perivascular cells expressing annexin A5 define a novel mesenchymal stem cell-like population with the capacity to differentiate into multiple mesenchymal lineages. Development. 2005 Jun;132(11):2657-68. Epub 2005 Apr 27. PubMed PMID: 15857912.

  44. Pöschl E, Schlötzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y, Mayer U. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development. 2004 Apr;131(7):1619-28. Epub 2004 Mar 3. PubMed PMID: 14998921.

  45. Brachvogel B, Dikschas J, Moch H, Welzel H, von der Mark K, Hofmann C, Pöschl E. Annexin A5 is not essential for skeletal development. Mol Cell Biol. 2003 Apr;23(8):2907-13. PubMed PMID: 12665588; PubMed Central PMCID: PMC152556.

  46. Brachvogel B, Reichenberg D, Beyer S, Jehn B, von der Mark K, Bielke W. Molecular cloning and expression analysis of a novel member of the Disintegrin and Metalloprotease-Domain (ADAM) family. Gene. 2002 Apr 17;288(1-2):203-10. PubMed PMID: 12034510.

  47. Brachvogel B, Welzel H, Moch H, von der Mark K, Hofmann C, Pöschl E. Sequential expression of annexin A5 in the vasculature and skeletal elements during mouse development. Mech Dev. 2001 Dec;109(2):389-93. PubMed PMID: 11731255.

  48. Dreier B, Fritz S, Volkert G, Brachvogel B, Lottspeich F, Fey GH. A 32-kDa proteolytic fragment of transcription factor Stat3 is capable of specific DNA binding. J Biol Chem. 1997 Aug 29;272(35):22118-24. PubMed PMID: 9268355.

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