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Carmen Ruiz de Almodóvar and the link between the nervous and vascular systems

Dr. Carmen Ruiz de Almodóvar from the Heidelberg University Biochemistry Centre has been awarded an ERC Starting Grant to study the molecular similarities between the nervous and vascular systems. The researcher showed that angiogenic factors such as VEGF also control the growth of neuronal cells and may be responsible for disorders in the development of nervous systems.

Neuronal wiring: a neuron and its dendrites © Universität Heidelberg

The excellent reputation of the European Research Council (ERC) funding programmes is largely due to the expertise and autonomy of the reviewers, who, independently from national, economic and research-policy related aspects, evaluate proposals solely on their quality and the scientific excellence of the applicants, who come from the entire European research area. The ERC owes this autonomy mainly to its founder and first president, Professor Fotis Kafatos. Kafatos, who was also the director general of the European Molecular Biology Laboratory (EMBL) between 1993 and 2005, and his colleague and former president of the German Research Foundation, Professor Ernst-Ludwig Winnacker, were instrumental in establishing and developing the ERC, which was officially inaugurated in 2007. Kafatos’ successor, Helga Nowotny, Professor emeritus at the ETH Zurich and ‘grande dame’ of European science research, is continuing Kafatos’ work as director of the ERC and of its funding programmes.

ERC Starting Grant awarded to Carmen Ruiz de Almodóvar

Dr. Carmen Ruiz de Almodóvar © Universität Heidelberg

ERC Starting Grants are available to researchers of any nationality with two to seven years’ experience since completion of their PhD and a highly promising scientific track record. Research must be conducted in a public or private research organisation located in one of the EU member states or associated countries. Being awarded an ERC Starting Grant means much more than simply receiving funding for a research project and gaining financial independence for up to five years. They are also a form of accolade in that they give up-and-coming scientists entry into top-level European research. Dr. Carmen Ruiz de Almodóvar Egea, a young Spanish researcher from the Heidelberg University Biochemistry Centre, has been awarded an ERC Starting Grant for a project entitled “Neurovascular communication in the neural tube during development”.

Schematic of signal transmission related to ‘axon guidance’ (explanations in the text). © University of Texas Southwestern

As different as they otherwise are, the nervous and vascular systems surprisingly have quite a number of characteristics in common and use similar signals and principles for growth, differentiation and spreading around the body. A specialised endothelial cell is located at the tip of a growing blood vessel. This cell reacts to signals from the environment and guides the growing blood vessel to its final destination. Nerve axons also have a specialised structure known as a growth cone, which receives and reacts to signals from the environment and guides the axon to its final destination (a process known as axon guidance). It is interesting to know that some of the signals are the same as those that control angiogenesis, i.e. the formation and targeted growth of new blood vessels. On the other hand, a key factor of angiogenesis, the vascular endothelial growth factor (VEGF), plays a key role in axon guidance, a discovery to which Ruiz de Almodóvar made a significant contribution. Little is known about the function of angiogenic factors in the development of the nervous system, the signalling pathways and the molecular basis of communication between the nervous and vascular systems. Using biochemical, cell- and molecular biology methods, mouse models and organotypic cultures, Carmen Ruiz de Almodóvar and her colleagues are studying the neurovascular link, i.e. the molecular connection between neurons and endothelial cells. The researchers are aiming to obtain a better understanding of the signalling pathways and cellular mechanisms used by angiogenic molecules to control neuronal cells, as well as of the communication between nervous and vascular systems during embryonic development.

Moving towards the neurovascular link

Carmen Ruiz de Almodóvar studied biochemistry at the University of Granada. She did her PhD at the Institute of Parasitology and Biomedicine “Lopez-Neyra” of the CSIC (Consejo Superior de Investigaciones Científicas/Spanish National Research Council), which is the largest research organisation in Spain. Articles on the results from her doctoral thesis on programmed cell death (apoptosis) in breast cancer cells and the effect of TRAIL – an apoptosis-inducing ligand similar to the tumour necrosis factor – have been published in a number of renowned scientific journals. After completing her PhD in 2004, Carmen Ruiz de Almodóvar became a post-doctoral fellow at the Vesalius Research Center led by Professor Peter Carmeliet at the Catholic University in Leuven (Belgium). Named after Andreas Vesalius (1514-1564), a famous Flemish Renaissance anatomist, the research centre, which is part of the Flemish Institute of Biotechnology (Vlaams Instituut voor Biotechnologie, VIB), has made a name for itself in the investigation of the molecular basis of angiogenesis and its medical importance. And it is where Carmen Ruiz de Almodóvar was introduced to the research topic for which she has now received the ERC grant.

At first sight, the nervous and vascular systems have little in common. Their functions are far too different: the vascular network, an interweaving network of capillaries, supplies all tissues with sufficient amounts of blood; the nerves originate in the CNS (brain and spinal marrow) and transmit electrical signals to the peripheral organs. Despite all these differences, the nerves and vessels of vertebrates, including humans, are closely linked anatomically, something Vesalius presented most impressively in his marvellous woodcut illustrations back in the 16th century. Nowadays, the term “neurovascular bundle” is applied to body nerves, veins, lymph vessels and arteries that travel together in the body, suggesting biological links between these organ systems.

“The human vascular system“ (left) and "The human nervous system” (right) from “De humani corporis fabrica” by Andreas Vesalius, 1543. © Berlin Museum of Medical History at the Charité

In Carmeliet’s laboratory in Leuven, Carmen Ruiz de Almodóvar and her colleagues discovered that VEGF and its receptors are also expressed in neurons and exert a regulatory function as they grow into the organs. This discovery provided the researchers with the basis for investigating neurovascular connections on the molecular level. The finding is also of great importance for medical reasons: VEGF-dependent signalling pathways are part of almost all types of diseases that involve angiogenic processes, including cancer, cardiovascular and inflammatory diseases. It is now known that VEGF is also involved in neurodegenerative diseases and that it has a direct influence on different types of nerve cells, including neural stem cells. VEGF relates to a family of proteins and genes whose components have different functions; due to their complex effects on intracellular signalling pathways, they are not yet understood in great detail.

From Leuven to Heidelberg

Following her post-doctoral period in Leuven, Carmen Ruiz de Almodóvar spent some time as visiting scientist in the laboratory of Professor Marc Tessier-Lavigne at Genentech, San Francisco, USA. Tessier-Lavigne, a renowned neuroscientist and long-standing chief scientific officer of the world’s first and foremost biotechnology company, was however appointed president of Rockefeller University in New York in 2011. Carmen Ruiz de Almodóvar moved on to Heidelberg where she became the head of a group of researchers at the Biochemistry Centre carrying out research into the “Molecular and cellular mechanisms of neuronal wiring, with a particular focus on the neurovascular link“. She is also a member of the Interdisciplinary Centre of Neurosciences at the University of Heidelberg. Carmen Ruiz de Almodóvar’s project, which is now strengthened by the ERC Starting Grant, brings together two areas for which research institutions in the Rhine-Neckar region are well known – the neurosciences and vascular research (see also BIOPRO article of July 7th 2010: Excellent vascular research in Baden-Württemberg). Due to her connections with the VIB Vesalius Research Center at the Catholic University in Leuven, Dr. Carmen Ruiz de Almodóvar and her involvement in research into the therapeutic potential of angiogenic factors in neurodegenerative diseases, is an excellent example of the European Health Axis (see BIOPRO article of October 17th 2011, A European Health Axis) which the BioRN network established between the well-known research locations of Heidelberg, Leuven and Cambridge. 

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