Published: 04-10-2013 00:00 | Updated: 13-02-2014 12:11

The Knut and Alice Wallenberg Foundation donates SEK 175 million to research at Karolinska Institutet

The Knut and Alice Wallenberg Foundation has announced its decision to finance six research projects at Karolinska Institutet. The foundation is to donate a total of SEK 174.9 million to research on changes in cerebral neurons, how the faulty regulation of the genome can lead to cancer and other diseases, new therapies for skin cancer, metabolic disorders of the brain, cardiovascular disease and inherited blood lipid disorders.

Maintaining neuronal identity - Transcriptional control of the aging brain

Professor Thomas Perlmann and his group at the Department of Cell and Molecular Biology have been granted SEK 40.4 million, to be shared with their collaboration partners, for a five-year study of how mature neurons retain their identities so that they may function properly in the adult brain.

"We'll be focusing on dopamine cells, which are degenerated in Parkinsons disease," says Professor Perlmann. "We'll be analysing dopamine cells in the normal and Parkinson's brain in order to understand in detail the genetic regulation mechanisms that determine the normal functioning of these cells in the ageing brain. Another important objective is to understand how changes in these mechanisms contribute to disease, and how these changes can be protected against in future clinical therapies."

Growth Control and Cancer

Professor Jussi Taipale at the Department of Biosciences and Nutrition is to receive SEK 38.9 million over five years to study the regulatory code in DNA strands that controls gene expression. The results will provide insight into the machinery that governs when and where genes are expressed, and the mechanisms that lead to diseases such as cancer, diabetes and cardiovascular disease.

"The primary purpose of the project is to crack the regulatory code so that we can read and understand the human genome," says Professor Taipale. "Using data generated through high-tech and data-intensive analyses, we'll discover how gene expression is regulated. Once we know this, the next step will be to create a model for how combinations of factors regulate gene expression in normal cells and, for example, cancer cells."

Novel treatment of advanced melanoma by targeted pro-senescence therapy combined with immunotherapy

Professor Lars-Gunnar Larsson at the Department of Microbiology, Tumour and Cell Biology is to receive SEK 33.6 million for a five-year research project aimed at finding better treatments for advanced melanoma, which is one of the fastest-growing tumour diseases and one of the most fatal. Every year, over 2,800 new cases are diagnosed in Sweden, with 500 recorded deaths.

"It appears as if advanced metastasising cancer diseases also develop a resistance to targeted and immune-stimulating melanoma therapies, and so new strategies are needed for beating these forms of cancer," says Professor Larsson.

"One of the body's most important defence mechanisms against cancer is senescence, which prevents the further division of tumour cells. Pro-senescence therapy is a new field in tumour biology and well be examining whether its combination with immune therapy can have synergic effects able to improve treatments for advanced melanoma."

Novel treatments for metabolic disorder of the brain

Professor Anna Wedell has been awarded a research grant of SEK 26.4 million for a five-year project studying metabolic disorders of the brain. Metabolic disorders are caused by disruption to physiochemical processes, and because of the brains sensitivity to such problems, most metabolic disorders cause brain damage if not caught in time. Common symptoms are retarded development, epilepsy or acute states of crisis that can even lead to premature death. The diseases are potentially treatable, but detailed knowledge of the pathogenic mechanisms is needed before new therapies can be developed.

"So far we've discovered two completely new metabolic diseases, findings that have given us fundamentally new knowledge of brain metabolism," says Professor Wedell. "We'll now be bringing together four research teams, and giving them unique opportunities to conduct in-depth studies into new disease mechanisms in patients with brain-impacting metabolic disorders. The aim is to develop new therapies for this large group of patients."

The Karolinska CardioVascular Initiative (KCVI)

Professor Kenneth Chien at the Department of Cell and Molecular Biology is to receive a three-year grant of SEK 24.7 million for four research projects into the pathogenesis and treatment of cardiovascular disease.

Cardiovascular disease is the most common cause of death in the West and accounts for approximately 40 per cent of deaths in Sweden. The aims of the research include producing a "molecular encyclopaedia" of the structure of different human cardiac cells in order to chart the hereditary contributors to cardiovascular disease; and stepping up successful trials using synthetic mRNA on mice to trials using human subjects.

"In our research on mice, we've managed to get cardiac muscle cells to express a certain growth factor that makes the heart's stem cells produce new blood vessels so that the heart can heal itself after suffering an infarction," says Professor Chien. "We think that it's possible to use the heart as a factory for producing growth factors for a specific group of stem cells, which suggests that we can create new heart tissue without adding any new cells to the heart."

Discovering new forms of monogenic hyperlipidemias by whole genome sequencing in families with extreme metabolic phenotypes

Professor Bo Angelin at the Department of Medicine in Huddinge is to receive SEK 10.8 million for a two-year project identifying the mechanisms that determine why a predisposition for increased levels of blood lipids is hereditary. Raised levels of blood lipids (cholesterol and triglycerides) are associated with an increased risk of myocardial infarction, stroke and premature death. Such inherited diseases, where fifty per cent of the children born of affected parents inherit the disposition, are estimated to be present in two per cent of the population. In most cases, the cause is unknown at a molecular level, something that is necessary for optimal diagnosis and early treatment, not least for symptom-free children and adults.

"Inherited blood lipid disorders are a common reason why relatively young individuals suffer from cardiovascular disease," says Professor Bo Angelin. "The disease requires early discovery and treatment, and our research will improve diagnostic and therapeutic techniques for this important patient group. If we can identify new disease-related genetic mutations, we'll also be able to develop new drugs of benefit to larger patient groups with high cardiovascular risk."

Knut and Alice Wallenberg Foundation