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Vascular Oncology and Metastasis

Division of Vascular Oncology and Metastasis

Prof. Dr. Hellmut Augustin

Three dimensional fluorescent microscopic view of subcutaneous blood vessels
© dkfz.de

Our laboratory studies the interactions between tumor cells and blood and lymphatic vessels during tumor progression and metastasis, as it relates to the growth of blood vessels in tumors. Angiogenesis, the sprouting of new blood vessels from existing vessels, is an oncofetal process that occurs physiologically during development and postnatal growth, but in adults is mostly restricted to pathological processes, which makes it an attractive target. Angiogenesis is characterized by molecular and cellular events which enable cells of the vessel wall (endothelial cells) to sprout from a pre-existing capillary to form new capillaries, which could then form a vascular network that matures over time with the recruitment of perivascular mural cells (smooth muscle cells, pericytes). We study the essential role of Angiopoietin/Tie signaling in blood and lymphatic vessels and analyze the molecular and functional properties of endothelial cells and pericytes during physiological and pathological angiogenesis and vessel remodeling. Given the critical roles of blood and lymphatic dysfunction for numerous oncological and non-oncological diseases, this work is aimed at better understanding the complexity of vessel functions to pave the way for rational therapeutic exploitation.

FUTURE OUTLOOK:
Molecules of the Angiopoietin/Tie ligand/receptor family exert gatekeeper functions within the vascular system to control tissue homeostasis and serve metabolic maintenance functions. Future work of the laboratory will be aimed at better understanding the molecular mechanisms of the vessel wall in the control of tissue homeostasis, most notably as it relates to maintenance and repair processes. Experimental approaches include (i) the vascular control of liver regeneration and liver tumorigenesis, (ii) the role of blood vessels in contributing to fibrotic tissue remodeling, (iii) the role of the vasculature in controlling tissue metabolism, including obesity, (iv) the role of blood vessels during aging and the role of vessel wall resident and bone marrow-derived stem cells during this process, and (v) the role of blood vessels in mediating the metastatic dissemination of circulating tumor cells. The lab will further intensify its efforts to elucidate the molecular and functional properties of the least well understood cells of the vessel wall, the perivascular pericytes, a cell type lining the outer surface of capillaries. We will study pericyte-endothelial interactions in depth to unravel pericyte function during pathological conditions including fibrosis and tumor progression.

Contact

Prof. Dr. Hellmut Augustin
Vascular Oncology and Metastasis (A190)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 1500

Selected Publications

  • Singhal M, Gengenbacher N, La Porta S, Gehrs S, Shi J, Kamiyama M, Bodenmiller DM, Fischl A, Schieb B, Besemfelder E, Chintharlapalli S, Augustin HG: Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking anti¬body. EMBO Mol Med, 12:e11164, 2020.
  • Singhal S#, Liu X#, Inverso D, Jiang K, Dai J, He H, Bartels S, Li W, Abdul Pari, AA, Gengenbacher N, Besemfelder E, Hui L, Augustin HG*, Hu J*: Endothelial cell fitness dictates the source of rege¬ne¬rating liver vasculature. J Exp Med, 215: 2497-2508, 2018 (#equally contributing first authors; *equally contributing last authors).
  • Schlereth K, Weichenhan D, Bauer T, Heumann T, Giannakouri E, Lipka D, Jaeger S, Schlesner M, Aloy P, Eils R, Plass C*, Augustin HG*: The transcriptomic and epigenetic map of vascular quiescence in the continuous lung endothelium. Elife, pii:e34423, 2018 (*equally contributing last authors).
  • La Porta S, Roth L, Singhal M, Mogler C, Spegg C, Schieb B, Qu X, Adams RH, Baldwin HS, Savant S, Augustin HG: Endothelial Tie1-mediated angiogenesis and vascular abnormalization promote tumor progression and metastasis. J Clin Invest, 128: 834-845, 2018
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