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Holger Gerhardt, Ph.D.

Vascular Biology Laboratory, London Research Institute –
Cancer Research UK, London, UK
Vascular Patterning Laboratory, VRC, VIB, Leuven, Belgium

gerhardtlabsfrance

From left to right:
Veronique Gebala, Filipa Neto, Irene Aspalter, Li-Kun Phng, Fabio Stanchi, Russell Collins, Holger Gerhardt, Anne-Clemence Vion, Anan Ragab, Ilse Geudens, Pavel Nedvetsky, Thomas Mathivet, Martin Jones, Marly Balcer.

Primary Research:
The Gerhardt lab is a joint venture between the Vascular Biology Lab (VBL) in London and the Vascular Patterning Lab (VPL) in Leuven seeking to foster new insights by establishing an interdisciplinary team that can draw inspiration from the diverse scientific environment present at the LRI and the VIB. This "two in one" approach provides broad access to technology and helps linking basic studies in vascular patterning with disease models while providing opportunities for close interactions with clinician scientists. It is our vision to build synergy and teamwork across the institutions in order to unravel the fundamental principles and molecular control of vascular patterning in development and disease.

Our primary research aims to take vascular cell biology into the in vivo situation by using a combination of imaging and increasingly selective single cell approaches in mouse and zebrafish that highlight the behavior of endothelial cells and their coordination to achieve functional vessel morphogenesis. In collaboration with many colleagues in the field we search ways to image molecules, cells and networks across time and space; from subcellular processes in individual cells with sub-second resolution in order to study mechanisms of cell guidance, shape change, polarity and signaling to whole vascular network level over the course of embryonic or postnatal development in order to understand how formation and remodeling of the network is orchestrated in tight association with vascular function. Recent work from our lab unraveled unexpected social behaviors at the cellular level in angiogenic sprouts (Jakobsson et al., NCB, 2010). Endothelial cells compete for the tip, continuously shuffle and rearrange, and appear to dynamically coordinate their behavior to achieve network formation. Ongoing studies place a feedback between VEGF and Notch signaling at the heart of collective endothelial behavior, and new dynamic insights begin to unravel the complexity and systems level integration of Notch signaling into the fundamental mechanisms of vascular branching. Spatial computational modeling in iteration with experimentation helps us to develop and refine hypotheses that in turn further push our efforts in imaging and quantitative analysis. We see important challenges ahead in the integration of signaling and physical forces experienced by the individual endothelial cells as they transit from leading tip cells to lumen forming stalk cells. Understanding how genetics and blood flow combine to shape the vascular tree is of fundamental importance not only for cardiovascular disease, but for all aspects of larger scale tissue engineering efforts.

We envision that the incorporation of multiple approaches and the cross-institutional "two in one" configuration will bring us closer to a comprehensive understanding of vascular morphogenesis in physiological and non-physiological angiogenesis and therefore also closer to new approaches in therapy.

If you want to know more about our work and us check out the VPL and the VBL homepage. Or, even better, read our recent papers and find out why a single endothelial cell forming a lumen can suddenly collapse (Martin et al., EMBO J, 2013), why some migrating endothelial cells do just fine in vivo without filopodia (Phng et al., Development, 2013), and much more.

Lab Members:

Dr Holger Gerhardt (Group Leader)
Dr Russell Collins (Senior Scientific Officer)
Dr Anan Ragab (Senior Scientific Officer)
Dr Raquel Blanco (Research Fellow)
Dr Claudio Areias Franco (Research Fellow)
Dr Martin Jones (Research Fellow)
Dr Andrea Taddei (Research Fellow)
Irene Aspalter (Graduate Student)
Véronique Gebala (Graduate Student)
Filipa Neto (Graduate Student)
Benedetta Ubezio (Graduate Student)
Dr Fabio Stanchi (Staff Scientist)
Dr Ilse Geudens (Post-doctoral Scientist)
Dr Li-Kun Phng (Post-doctoral Scientist)
Dr Pavel Nedvedsky (Post-doctoral Scientist)
Marly Balcer (Lab Technician)

Number of trainees in the laboratory: 7 postdoctoral fellows, 4 graduate students

Former lab members:
Eleonora Lapi, Andrin Wacker, Katie Bentley

Laboratory Web sites:

http://www.london-research-institute.org.uk/research/holger-gerhardt

http://www.vib.be/en/research/scientists/Pages/Holger-Gerhardt-Lab.aspx

Recent Publications:

Franco CA, Blanc J, Parlakian A, Blanco R, Aspalter IM, Kazakova N, Diguet N, Mylonas E, Gao-Li J, Vaahtokari A, Penard-Lacronique V, Fruttiger M, Rosewell I, Mericskay M, Gerhardt H*, Li Z*. SRF selectively controls tip cell invasive behavior in angiogenesis. Development. 2013;140(11):2321-2333.*co-corresponding authors

Martin M, Geudens I, Bruyr J, Potente M, Bleuart A, Lebrun M, Simonis N, Deroanne C, Twizere JC, Soubeyran P, Peixoto P, Mottet D, Janssens V, Hofmann WK, Claes F, Carmeliet P, Kettmann R, Gerhardt H*, Dequiedt F*. PP2A regulatory subunit Bα controls endothelial contractility and vessel lumen integrity via regulation of HDAC7. EMBO J. 2013;32(18):2491-503.*co-corresponding authors

Phng LK, Stanchi F, Gerhardt H. Filopodia are dispensable for endothelial tip cell guidance. Development. 2013;140(19):4031-40

Guarini V, Deflorian G, Franco CA, Kruger M, Phng LK, Bentley K, Toussaint L, Dequiedt F, Mostoslavsky R, Schmidt MHH, Zimmermann B, Brandes RP, Mione M, Westphal CH, Braun T, Zeiher AM, Gerhardt H, Dimmeler S, Potente M. Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature. 2011;473(7346):234-8

Potente, M., Gerhardt, H., and Carmeliet, P. (2011). Basic and therapeutic aspects of angiogenesis. Cell 146, 873-887.

Stenzel D, Franco CA, Estrach S, Mettouchi A, Sauvaget D, Rosewell I, Schertel A, Armer H, Domogatskaya A, Rodin S, Tryggvason K, Collinson L, Sorokin L, Gerhardt H. Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. EMBO Rep. 2011 Oct 7. doi: 10.1038/embor.2011.194

Stenzel, D., Lundkvist, A., Sauvaget, D., Busse, M., Graupera, M., van der Flier, A., Wijelath, E.S., Murray, J., Sobel, M., Costell, M., Takahashi, S., Fassler, R., Yamaguchi, Y., Gutmann, D.H., Hynes, R.O., and Gerhardt, H. (2011). Integrin-dependent and -independent functions of astrocytic fibronectin in retinal angiogenesis. Development 138, 4451-4463

Jakobsson L, Franco CA, Bentley K, Collins RT, Ponsioen B, Aspalter IM, Rosewell I, Busse M, Thurston G, Medvinsky A, Schulte-Merker S, Gerhardt H. Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol. 2010;12(10):943-53

Bentley K, Mariggi G, Gerhardt H, Bates PA. Tipping the balance: robustness of tip cell selection, migration and fusion in angiogenesis. PLoS Comput Biol. 5:e1000549