Fixing leaking capillaries

Sepsis, previously known as blood poisoning, continues to be a common, occasionally lethal disease, which is primarily associated with the breakdown of blood vessel walls. Associate Professor Pipsa Saharinen hopes to create a method which would keep the blood vessel walls intact and blood where it belongs. The European Research Council has granted Saharinen’s ANTILEAK project a five-year €2-million ERC Consolidator Grant.

The central factor in sepsis, and particularly its more severe form, septic shock, is the breakdown of the walls in the capillary vessels, which leads to fluid oozing into the tissue. The increased permeability of capillary walls is also associated with many other common diseases. The blood vessels of cancer tumours are also permeable, which makes drugs less effective in cancerous tissue.

So far, it has been impossible to develop precision treatment of the “leaking” blood vessels, as there has been insufficient background information on the phenomenon.

Illnesses associated with blood vessel leakage constitute a global health problem, afflicting tens of millions of people every year.

Associate Professor Pipsa Saharinen has concentrated on examining the molecular mechanisms that regulate the permeability of blood vessel walls, and her team has now made a significant discovery:

“We’ve identified what may be a key mechanism in the chain of events that results in excessive vascular permeability. With a precision treatment targeting this mechanism, we might be able to halt this detrimental process,” says Saharinen.

The European Research Council has granted Saharinen’s ANTILEAK project a five-year €2-million ERC Consolidator Grant.

There is tremendous need for a drug that could prevent blood vessel leakage.

“Illnesses associated with blood vessel leakage constitute a global health problem, afflicting tens of millions of people every year. These are also very serious illnesses,” Saharinen states.

Breaking dangerous signal chains

The growth factor known as angiopoietin-2, which regulates the generation of blood vessels, is known to also contribute to the regulation of the permeability of blood vessel walls. The Ang2 growth factor controls the cell functions through the Tie2 receptor.

However, Saharinen’s team have found another pathway in addition to the Tie2 channel, which allows Ang2 to send orders to the cell and trigger a process that may lead to blood vessel leakage.

As Ang2 is a key factor in the generation of blood vessels associated with cancer, it was identified as an important target for drug treatment already years ago, and drugs inhibiting its function are in clinical trials.

“At the moment, the drugs in the clinical trials only block the Tie2 signalling pathway, leaving the pathway we discovered open. This could explain why these drugs have not been as effective as could be expected,” says Saharinen.

Pipsa Saharinen hopes to develop antibodies that would allow the control of the signalling chains that regulate blood vessel walls to prevent them from becoming too permeable.

“It would be a major leap in the development of next-generation blood vessel medication.”

Saharinen Lab

University of Helsinki has now over 60 ERC projects. For more information, see research fun­ded by European Research Coun­cil ERC.
European Research Council Grants for five researchers

Five researchers from the University of Helsinki have received the European Research Council’s (ERC) Consolidator Grant.

The Grants are awarded to outstanding researchers with at least seven and up to twelve years of experience after PhD, and a scientific track record showing great promise. On this application round, the total of €630 million euros was awarded to 329 top researchers around Europe. In addition to Pipsa Saharinen, the new ERC grantees at the University of Helsinki are:

Tuomas Tahko, Faculty of Arts

Tuomas Tahko’s research project will pursue the question of what, if anything, unifies the natural sciences from the perspective of metaphysics and philosophy of science. He employs case studies from biology, chemistry, and physics to investigate what does it mean for one scientific phenomenon to be explained in terms of another and under what conditions does scientific unification take place?

“In philosophy, these questions are often discussed under the rubric of reduction. Typically, in asking whether one phenomenon reduces to another, we aim to understand what the ultimate or fundamental basis of the first phenomenon is,” Tahko says.

The research project’s goal is to produce a novel account of unification. A cross-disciplinarily applicable toolbox for unification would be useful for identifying the kind of expertise is needed for understanding a given phenomenon.

Jörg Tiedemann, Faculty of Arts

The goal of Jörg Tiedemann’s research is to develop models for natural language understanding trained on implicit information given by large collections of human translations. His research team will apply massively parallel data sets of over a thousand languages to acquire abstract meaning representations that can be used for reasoning with natural languages and for multilingual neural machine translation.

“Natural language understanding is the holy grail of computational linguistics and a long-term goal in research on artificial intelligence," Tiedemann says.

Kaius Tuori, Faculty of Social Sciences

Kaius Tuori studies the European republican tradition from the perspective of public administrative space. Since the Roman Republic, the officials serving the people and the nation have been at the core of republican tradition.

By combining historical sources and archeological findings, Tuori’s group studies how the space given to public administration reflects its role in the society. In particular, the project investigates the relationship between private and public space and the place of public administration in between those two.

Sara Wickström, HiLIFE & Faculty of Medicine

Sara Wickström will move her research project from Max Planck Institute of Ageing to Helsinki Institute of Life Science HiLIFE. She studies how single cell behaviors are coordinated on the population level and how population-level dynamics is coupled to tissue architecture.

The breakthrough innovation has been developing a method to cultivate hair follicle stem cells that fuel hair follicle regeneration, repair epidermal injuries and, when deregulated, initiate carcinogenesis.

By deconstructing complex tissue level behaviors at an unprecedented spatiotemporal resolution this study has the potential to transform the fundaments of adult stem cell biology with immediate implications to regenerative medicine.