Prof. Dr. Holger Gerhardt
Research areas: angiogenesis, tumour angiogenesis, vascular plasticity and patterning in development and disease, imaging
Prof. Gerhardt is DZHK Professor for Experimental Cardiovascular Research at the Charité Berlin and Head of the Integrative Vascular Biology Laboratory at Max-Delbrück Center for Molecular Medicine, Berlin-Buch.
Research focus
The Integrative Vascular Biology Laboratory aims to unravel the fundamental principles and molecular/genetic regulation of functional vascular network formation in development and disease. The ultimate goal of Prof. Gerhardt’s group’s research is the advancement of our understanding of mechanisms and molecules controlling the formation and patterning of a hierarchically branched vascular network such that we can inform, innovate and implement therapeutic approaches to mitigate cardiovascular complications and establish or restore tissue homeostasis in compromised patients. In their research efforts, the research group focuses on unraveling how endothelial cells collectively integrate mechanical and chemical stimuli to achieve functional vascular patterning and pave the way towards translational research into maladaptive behavior in disease.
To study these processes, the Integrative Vascular Biology Laboratory develops and uses genetic tools to image and manipulate molecules, complexes, and cells in a spatiotemporal controlled manner in vivo in mouse and zebrafish models. Prof. Gerhardt’s group further uses iteration between predictive computational modeling and experimentation to develop hypotheses and systems-level understanding of the processes at play.
Key findings of the past few years include the discovery of the mechanism of vascular lumen formation by inverse membrane blebbing under blood pressure, the identification of a phase transition in Notch signaling dynamics that switch blood vessel formation from branching to expansion, a role for YAP/TAZ signaling in controlling junctional dynamics and plasticity to enable endothelial cell rearrangements while keeping vessels tight, and a role of primary cilia in endothelial cells sensitizing nascent vessels to the stabilizing activity of BMP under blood flow.
Additionally, Prof. Gerhardt is the Vice-spokesperson of the DZHK Partnersite Berlin and Speaker of the DZHK Professors. He also holds a Professorship at the Berlin Institute of Health and is the European coordinator for the Fondation Leducq transatlantic network of excellence ATTRACT.
Major achievements and awards
- Chair Gordon Research Conference Angiogenesis (2015)
- Hooke Medal of the British Society for Cell Biology (2012)
- Judah Folkman Award of the North American Vascular Biology Organization (2011)
- Walter Flemming Medal of the German Society for Cell Biology (2009)
- Lister Institute of Preventive Medicine Prize (2008)
Key publications
Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways. Gloger, M., Menzel, L., Grau, M., Vion, A.C., Anagnostopoulos, I., Zapukhlyak, M., Gerlach, K., Kammertöns, T., Hehlgans, T., Zschummel, M., Lenz, G., Gerhardt, H., Höpken, U.E., Rehm, A. Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways. Cancer Res, 2020. (in Press)
Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1. Zhao, X., Nedvetsky, P., Stanchi, F., Vion, A.C., Popp, O., Zühlke, K., Dittmar, G., Klussmann, E., Gerhardt, H. Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1. eLife 8: e46380, 2019.
Artery-vein specification in the zebrafish trunk is pre-patterned by heterogeneous Notch activity and balanced by flow-mediated fine tuning. Geudens, I., Coxam, B., Alt, S., Gebala, V., Vion, A.C., Meier, K., Rosa, A., Gerhardt, H. Artery-vein specification in the zebrafish trunk is pre-patterned by heterogeneous Notch activity and balanced by flow-mediated fine tuning. Development 146(16): dev.181024, 2019.
ATTRACT: arterial flow as attractor for endothelial cell migration. Georgieva, P.B., Marchuk, D.A., Gerhardt, H. Circ Res 125(3): 262-264, 2019.
GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients. Hu, X., Matsumoto, K., Jung, R.S., Weston, T.A., Heizer, P.J., He, C., Sandoval, N.P., Allan, C.M., Tu, Y., Vinters, H.V., Liau, L.M., Ellison, R.M., Morales, J.E., Baufeld, L.J., Bayley, N.A., He, L., Betsholtz, C., Beigneux, A.P., Nathanson, D.A., Gerhardt, H., Young, S.G., Fong, L.G., Jiang, H. GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients. eLife 8: e47178, 2019.
Development of a backward-mode photoacoustic microscope using a Fabry-Pérot sensor. Pohle, U., Baumann, E., Pulwer, S., Villringer, C., Zhang, E.Z., Gerhardt, H., Laufer, J. Development of a backward-mode photoacoustic microscope using a Fabry-Pérot sensor. Proc SPIE 10878: 108786L, 2019.
Endothelial calcineurin signaling restrains metastatic outgrowth by regulating Bmp2. Hendrikx, S., Coso, S., Prat-Luri, B., Wetterwald, L., Sabine, A., Franco, C.A., Nassiri, S., Zangger, N., Gerhardt, H., Delorenzi, M., Petrova, T.V. Endothelial calcineurin signaling restrains metastatic outgrowth by regulating Bmp2. Cell Rep 26(5): 1227-1241, 2019.
Imaging glioma progression by intravital microscopy. Stanchi, F., Matsumoto, K., Gerhardt, H. Imaging glioma progression by intravital microscopy. Methods Mol Biol 1862: 227-243, 2019.
Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility. Angulo-Urarte, A., Casado, P., Castillo, S.D., Kobialka, P., Kotini, M.P., Figueiredo, A.M., Castel, P., Rajeeve, V., Milá-Guasch, M., Millan, J., Wiesner, C., Serra, H., Muixi, L., Casanovas, O., Viñals, F., Affolter, M., Gerhardt, H., Huveneers, S., Belting, H.G., Cutillas, P.R., Graupera, M. Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility. Nat Commun 9(1): 4826, 2018.
NanoSIMS imaging reveals unexpected heterogeneity in nutrient uptake by brown adipocytes. He, C., Hu, X., Weston, T.A., Jung, R.S., Heizer, P., Tu, Y., Ellison, R., Matsumoto, K., Gerhardt, H., Tontonoz, P., Fong, L.G., Young, S.G., Jiang, H. NanoSIMS imaging reveals unexpected heterogeneity in nutrient uptake by brown adipocytes. Biochem Biophys Res Commun 504(4): 899-902, 2018.
Further information
Fondation Leducq Transatlantic Network of Excellence ATTRACT
CRC1366 Vascular Control of Organ Function