“We explore the novel functions of blood vessels during development and ageing”
The vertebrate body undergoes physiological changes during development, growth and ageing. Changes in body tissues are accompanied by changes in the organisation of nearby blood vessels. For example, when a tissue undergoes repair and regeneration, or becomes diseased, the organisation of blood vessels within that tissue will change. This suggests that blood vessels play a critical role in maintaining homeostasis, a functional equilibrium within a tissue.
In addition to their role as a transport network, blood vessels have recently been shown to regulate the process in which organs develop, organogenesis, and in which they establish their structure, tissue morphogenesis. They do this by providing molecular signals and growth factors to neighbouring cells in a tissue.
We also aim to understand the role of blood vessels in regulating the physiological functions of the skeletal system. The skeletal system provides mechanical support and is involved in blood cell production, mineral homeostasis and metabolism. It has a range of blood vessel subtypes, each with distinct microenvironments. We investigate the specific interactions between blood vessels and the surrounding bone tissue using a combination of novel approaches such as advanced 3D imaging, intra-vital imaging, transcript profiling and cell-specific inducible mouse genetics.
The ultimate goal of our research is to identify novel therapeutic strategies to manage ageing and age-related bone and blood diseases.
Saravana Ramasamy holds a Sir Henry Dale Fellowship.
Romeo SG, Alawi KM, Rodrigues J, Singh A, Kusumbe A, Ramasamy S. (2019). Endothelial proteolytic activity and interaction with non-resorbing osteoclasts mediate bone elongation. Nature Cell Biology 21, 430-441.
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.
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 Reports 18, 1804-1816.
Gamrekelashvili J, Giagnorio R, Jussofie J, Soehnlein O, Duchene J, Briseno CG, Ramasamy SK, Krishnasamy K, Limbourg A, Hager C, Kapanadze T, Ishifune C, Hinkel R, Radtke F, Strobl LJ, Zimber-Strobl U, Napp LC, Bauersachs J, Haller H, Yasutomo K, Kupatt C, Murphy KM, Adams RH, Weber C, Limbourg FP. (2017). Regulation of monocyte cell fate by blood vessels mediated by Notch signalling. Nature Communications 8, 15486.
Ramasamy SK. (2017). Structure and Functions of Blood Vessels and Vascular Niches in Bone, Stem Cells International.
Kusumbe AP, Ramasamy SK, Itkin T, Mäe MA, Langen UH, Betsholtz C, Lapidot T, Adams RH. (2016). Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature 532, 380-384. doi: 10.1038/nature17638.
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. Nature Communications, 7.
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, 323-328. doi: 10.1038/nature17624.
Ramasamy SK, Kusumbe AP, Adams RH. (2015). Regulation of tissue morphogenesis by endothelial-derived signals. Trends Cell Biology 52, 148-157. doi: 10.1016/j.tcb.2014.11.007.
Ramasamy SK*, Kusumbe AP*, Wang L, Adams RH. (2014). Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature 507, 376-380. doi: 10.1038/nature13146.
Kusumbe AP*, Ramasamy SK*, Adams RH. (2014). Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507, 323-328. doi: 10.1038/nature13145.