Research related to fibrotic diseases is one of the profiling themes of research conducted at the University of Oulu. The Academy of Finland decided to fund a research entity called Fibrosis Diseasome in summer 2017. This entity is managed by the Scientific Director of Biocenter Oulu Professor Johanna Uusimaa.
The University of Oulu has strong traditions in the research of extracellular matrix, one example being the Center of Excellence in Cell-Extracellular Matrix Research in 2012–2017 coordinated by our university.
“Fibrosis-related research is already at a very high level at our university. Another strengths of ours are the unique population and patient cohorts,” says Uusimaa.
A phenomena where previously healthy tissue turns into scar tissue, as the result of either infection, tissue damage or some other reason, which often remains unknown, is called fibrosis. In the worst case, this may result in organ damage and even death.
Fibrosis plays a significant role in several chronic diseases. These include obesity, diabetes, pulmonary and cardiac diseases, fatty liver, chronic kidney disease, musculoskeletal diseases, different skin diseases and degenerative neurological diseases. Many of these diseases are becoming increasingly common with the ageing of the population, which creates challenges for the health care services.
For now, there is no preventative or curing treatment available for fibrosis and medication at best only slows down its progression. In some cases, an organ transplant may be an option where the fibrotic organ, such as the liver or lungs, is replaced with a healthy organ coming from a donor.
Reasons leading to the development of fibrosis vary according to patient groups and, in practice, the disease of every single patient is very unique.
“Since the development mechanisms of fibrotic diseases are very different, very diverse multidisciplinary research is also needed,” Uusimaa says.
The research will generate data on the molecular biological and epidemiological background of fibrosis in complex chronic diseases. The goal is to learn to understand the development mechanisms of fibrosis and to recognise fibrosis at a very early stage.
“This way we will be able to develop markers of the early stage that will enable the follow-up of the clinical situation and treatment response, more individualised treatment and the development of completely new treatments,” says Uusimaa.
Scattered research as a challenge
Currently at the University of Oulu, fibrosis-related research is conducted in 11 different research units at three faculties, which are the Faculty of Biochemistry and Molecular Medicine, Faculty of Medicine and Faculty of Humanities. In addition, research is conducted at two strategic focus institutes of the university, Biocenter Oulu and Eudaimonia, as well as at the Medical Research Center (MRC) Oulu, which is a collaborative organisation of the Oulu University Hospital and University of Oulu.
The outpatient clinics of Oulu University Hospital treat and examine, for example, cardiac and liver fibrosis, fibrotic lung diseases and many rare diseases involving tissue fibrosis.
According to Uusimaa, clinical fibrosis research in particular has been scattered, and bringing fibrosis researchers of different fields together is among the key future objectives.
“The challenge is to strengthen both research coordination and cooperation among researchers, thus enabling the creation of increasingly multidisciplinary research entities.”
Funding to enable top-level recruitment
Since January 2019, profiling funding from the Academy of Finland has been used to recruit experts for two tenure track positions. Professor Vesa Kiviniemi operates in the field of clinical neuroradiology at the Faculty of Medicine and Associate Professor Zhi Jane Chen in the field of immunology at the Faculty of Biochemistry and Molecular Medicine. In addition, two experts will start in tenure track positions in August, Professor Aki Manninen at the Faculty of Biochemistry and Molecular Medicine and Associate Professor Reetta Hinttala at the Faculty of Medicine.
The fibrosis profiling theme has also been taken into account in many other new recruitments and appointments of professors to emphasise the subject area.
Four tenure track researchers
The fibrosis research of Functional Neuroimaging Professor Vesa Kiviniemi involves operational changes in the brain’s waste clearance pathway, i.e. glymphatic system, due to brain gliosis, which is a condition similar to fibrosis in the brain. Kiviniemi is known as a pioneer in the MRI imaging of spontaneous activation of the brain. The independent component analysis (ICA) that he was the first to apply in the differentiation of the brain’s spontaneous activation from the physiological pulsations in the late 1990s has become the object of increasing research in the past years.
Kiviniemi is one of the pioneers in the MRI imaging of spontaneous activation of the brain in the world. His research group demonstrated that, in addition to the human brain artery pulsation, respiratory pulsation and slow vasomotor waves also serve as power sources in the glymphatic system of the brain.
Associate Professor Jane Chen’s objective is to learn to understand the immunological mechanisms related to fibrosis. Her interests involve the role and activity of the so-called helper T cells in chronic inflammation and in the development of fibrosis. Understanding the function of the cells is important, for example, in the development of new medications.
Chen arrived to Oulu in January. She originally graduated from Beijing Medical University (currently Peking University Health Science Center). Chen completed her doctor's degree at the University of Turku. Since then, she has been working as a postdoctoral researcher at the National Institutes of Health of the USA and as an Academy Research Fellow at the University of Turku.
The research group of Professor Aki Manninen is investigating abnormal interactions of prostate cancer cells with the surrounding tissue. Fibrotic changes of the interstitial tissue, i.e. stroma, surrounding the cancer cells play a key role in the regulation of prostate cancer cell growth and activity. On the other hand, cancer cells also actively modulate stromal cell behaviour and the surrounding extracellular matrix. According to Manninen, understanding this bidirectional communication will bring about new possibilities to prevent the progression of prostate cancer.
Manninen investigates changes in the prostate epithelial cells.
The research of Associate Professor Reetta Hinttala involves the recently described severe childhood multiorgan disease, which has been named, according to the main discoveries made in the patient tissue, as FINCA (Fibrosis, Neurodegeneration and Cerebral Angiomatosis). The disease is caused by mutations of the NHLRC2 gene. The objective of Hinttala’s research is to solve the function of the protein produced by the NHLRC2 gene and to establish how the mutations in the gene lead to pulmonary fibrosis, destruction of nerve cells and regeneration of blood vessels in the brain.
Hinttala investigates the function of the protein produced by the NHLRC2 gene with the help of cell and mice models. Hinttala also serves as Coordinator in Transgenic Core Facility of Biocenter Oulu.
“Grand Opening” seminar in October
The first joint scientific seminar of fibrosis researchers will be held at the University of Oulu on 15 October 2019. On that occasion, key researchers of the project will give presentations together with a group of top Finnish and foreign experts on the field.
The seminar also celebrates the long traditions of the University of Oulu in extracellular matrix research with the theme of “Over 50 years of extracellular matrix research”.
Author: Meri Rova
Photos: Seija Leskelä, Tiina Strand
Last updated: 24.6.2019