Regulation of blood-brain-barrier function by pericytes

    The function of the blood-brain barrier relies on close interactions between different cell types including endothelial cells, pericytes and astrocytes. Here, we propose to study the role of the transcriptional coactivators YAP/TAZ and the Hippo signaling pathway in brain pericytes with cell type-specific and inducible genetic approaches in mice, cell biology, RNA sequencing, and biochemistry experiments. The planned work will provide important novel insights into the functional properties of pericytes and their role in the regulation of the blood-brain barrier.

    Research area: Endothelial cell biology

    Prof. Dr. Ralf Adams

    Funding period: July 2016 - June 2020

    • Publications

      Original articles

      • Tikhonova AN, Dolgalev I, Hu H, Sivaraj KK, Hoxha E, Cuesta-Domínguez Á, Pinho S, Akhmetzyanova I, Gao J1, Witkowski M, Guillamot M, Gutkin MC, Zhang Y, Marier, Diefenbach C, Kousteni S, Heguy A, Zhong H, Fooksman DR, Butler JM, Economides A, Frenette PS, Adams RH, Satija R, Tsirigos A, Aifantis I (2019). The bone marrow microenvironment at single-cell resolution. Nature 569:222-228.
      • Duarte D, Hawkins ED, Akinduro O, Ang H, De Filippo K, Kong IY, Haltalli M, Ruivo N, Straszkowski L, Vervoort SJ, McLean C, Weber TS, Khorshed R, Pirillo C, Wei A, Ramasamy SK, Kusumbe AP, Duffy K, Adams RH, Purton LE, Carlin LM, Lo Celso C (2018). Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML. Cell Stem Cell. 22:64-77.
      • Kato K, Diéguez-Hurtado R, Park DY, Hong SP, Kato-Azuma S, Adams S, Stehling M, Trappmann B, Wrana JL, Koh GY, Adams RH (2018). Pulmonary pericytes regulate lung morphogenesis. Nat Commun. 9:2448. *work from the previous funding period of the CRC 1009.
      • Bixel MG, Kusumbe AP, Ramasamy SK, Sivaraj KK, Butz S, Vestweber D, Adams RH (2017). Flow Dynamics and HSPC Homing in Bone Marrow Microvessels. Cell Rep. 18:1804-1816.
      • Eilken HM, Diéguez-Hurtado R, Schmidt I, Nakayama M, Jeong HW, Arf H, ... & Adams RH (2017). Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1. Nature Communications, 8(1), 1574. (doi:10.1038/s41467-017-01738-3)
      • Langen UH, Pitulescu ME, Kim JM, Enriquez-Gasca R, Sivaraj KK, Kusumbe AP, Singh A, Di Russo J, Bixel MG, Zhou B, Sorokin L, Vaquerizas JM, Adams RH (2017). Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat Cell Biol. 19:189-201.
      • Itkin T, Gur-Cohen S, Spencer JA, Schajnovitz A, Ramasamy SK, Kusumbe AP, Ledergor G, Jung Y, Milo I, Poulos MG, Kalinkovich A, Ludin A, Kollet O, Shakhar G, Butler JM, Rafii S, Adams RH, Scadden DT, Lin CP, Lapidot T (2016). Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 532:323-8.
      • Kusumbe AP, Ramasamy SK, Itkin T, Mäe MA, Langen UH, Betsholtz C, Lapidot T, Adams RH (2016). Age-dependent modulation of vascular niches for hematopoietic stem cells. Nature 532:380-4.
      • Ramasamy SK, Kusumbe AP, Schiller M, Zeuschner D, Bixel MG, Milia C, Gamrekelashvili J, Limbourg A, Medvinsky A, Santoro MM, Limbourg FP, Adams RH (2016). Blood flow controls bone vascular function and osteogenesis. Nat Commun. 7:13601.