Academy of Finland Professor Kari Alitalo (b. 1952), head of the Translational Cancer Biology Research Programme and director of the Wihuri Research Institute, has discovered several growth factors that regulate the development of blood and lymphatic vessels as well as identified the receptors of messages from the growth factors. He has also studied growth factor and receptor use in the treatment of illnesses.

In the 1990s, Alitalo and his research group discovered the receptors VEGFR-3 and Tie1, which receive growth factor messages, as well as the first lymphatic vessel growth factor VEGF-C and, together with international partners, the growth factors VEGF-B and VEGF-D.

The researchers discovered that cellular messages that pass through lymphatic and blood vessels essentially follow the same logic in both systems. This observation proves that evolution is economical in its product development.

From re­search dis­cov­er­ies to forms of treat­ment

The findings have staggering application potential. In the future, treatment based on blood and lymphatic vessel growth factors could be mainstream for many illnesses.

Already cancer treatment seeks to block blood vessel growth factors to defeat tumours.

On the other hand, the growth of blood vessels could be accelerated in patients with cardiovascular diseases. This has already been established to help prevent heart attacks in animal models.

According to the latest results from Alitalo’s laboratory, diabetes associated with adult obesity (type 2 diabetes) could also be alleviated by increasing vascular growth factors. This is because the improved circulation allows insulin to better regulate blood sugar levels in fatty tissue, for example.

Growth factor research has also helped doctors strengthen blood vessel walls, a technique used, for example, in the treatment of lung trauma resulting from a car accident or in cases of blood poisoning in which blood serum leaks into tissues.

Occasionally, breast cancer will metastasise into the lymphatic nodes of the armpit.  After the metastatic tumours are surgically removed and the remaining cancer cells destroyed through radiation therapy, there will be scar tissue blocking the lymphatic vessels in the armpit, which may result in permanent tissue swelling in the arm. With the help of lymphatic vessel growth factors, new lymphatic vessels can be generated at the location of the scar, so that fluid can drain from the arm more freely. Such treatments are currently being developed by the Finnish pharmaceutical company Herantis.

A sci­ent­ist from child­hood

As a child, Alitalo began to study the hard sciences independently when his severe asthma restricted his hobbies and opportunities to spend the summer holidays outside. In the national mathematics competition for upper secondary school pupils, the young Alitalo shared the first prize, but went on to study medicine at his father’s recommendation.

Alitalo received his doctorate in 1981 as the highest ranking doctoral graduand of the conferment ceremony, while working at Antti Vaheri's laboratory in the University of Helsinki's Department of Virology. In his dissertation, Alitalo determined how cancer viruses found in chickens can change the way normal cells attach to the extracellular matrix.

Can­cer ge­net­ics in San Fran­cisco

After receiving his doctorate, Alitalo moved to San Francisco to the laboratory of the famous cancer researcher Michael Bishop, where he was the first to image the Myc oncogene and oncoprotein from the Finnish OK10 virus (Oker Blom-Kallio 10) he had brought with him. Alitalo asked Bishop for permission to find genes that would correspond to the chicken oncogenes from the abnormal chromosomes of cancerous cells – and found duplicates of the Myc cancer gene.

However, a previously unknown disease began to spread in San Francisco, killing young men in particular, with even a young child becoming infected after a transfusion. It was partially for this reason that Alitalo sent his family back to Finland and followed them in 1983.

Bishop and his colleague from the same laboratory, Harold Varmus, later received a Nobel prize for discovering the cancer genes.

The epidemic that frightened the Alitalos was later understood to be AIDS, but Alitalo stayed in Finland, although he travels widely for work.

Rais­ing the next gen­er­a­tion of re­search­ers

Over the decades, Alitalo has held many different professorships and research leadership positions. He has supervised more than 40 doctoral dissertations and has mentored seven professors and numerous generations of researchers, whose career development Alitalo feels both responsible for and proud of.

In 2015 the scientific world was shaken when young researchers in Alitalo’s group, Aleksanteri Aspelund and Salli Antila, found that unlike what is commonly believed, there are, in fact, lymphatic vessels in the meninges. This discovery may lead to new innovations in the treatment of conditions such as degenerative memory diseases.

Kari Alitalo: Publications, projects, activities

Kari Alitalo Lab: Translational Cancer Biology Research Program

 

During his extensive career, Heikki Joensuu (*1956), professor of clinical oncology and research director at the Helsinki University Hospital Comprehensive Cancer Center, has developed effective precision drugs for many forms of cancer.

In 2000, Joensuu and his colleagues were the first in the world to discover that Imatinib, a drug used to treat leukaemia, was also effective against gastrointestinal stomach tumours, or GISTs. Before this, there was no effective treatment available for this relatively rare form of cancer.

At the Department of Oncology, Joensuu experimented using Imatinib on a patient with GIST, and the drug was dramatically effective in destroying the tumour.

During the following year, 147 GIST patients were treated with Imatinib in a collaborative study between the University of Helsinki and three American universities. Approximately 90% of the patients benefitted from the treatment and found that their quality of life improved. The drug was quickly approved in America as a treatment for GIST.

The efficacy of Imatinib was later confirmed in a series of randomised tests. It became a standard drug against GIST, and continues as such.

In 2012, Joensuu proved that treatment with Imatinib after GIST surgery radically reduced the likelihood of the cancer reoccurring.

The FinHer trial has also gained a great deal of attention.

In FinHer, breast cancer patients are given a drug known as Herceptin for a year after surgery to prevent regrowth of cancer tumours. However, laboratory experiments have indicated that the drug docetaxel increases the efficacy of Herceptin up to a hundredfold.

At the turn of the century, Joensuu and his colleagues established that a few weeks of combined treatment with Herceptin and docetaxel prevented the recurrence of cancer as effectively as a year’s course of Herceptin, and was associated with fewer cardiac side-effects

The price for the combination treatment is approximately €6,000, while a year of Herceptin can cost up to €35,000.

However, the study only involved 232 patients, and elsewhere, more extensive studies had established the efficacy of the year-long course. For this reason, the year-long course of Herceptin has become standard, also in Finland.

However, Joensuu and his colleagues have continued to study the combined treatment, using more extensive, international data.

As a drug researcher in the public sector, Joensuu considers it his responsibility to also study ways to reduce the costs of treatments. This could enable society to provide treatment to a greater number of patients.

Between 1995 and 2009, Joensuu was the chief physician of the Department of Oncology at the Helsinki University Hospital. Throughout his career, he has simultaneously studied cancer and treated cancer patients.

As a researcher, he considers it important to see the patients and the effects of the drugs, and as a physician, he finds it useful to know the researchers and the latest results in the field.

Heikki Joensuu: Publication, projects and Activities

Jaakko Kaprio (*1952), Academy of Finland Professor of genetic epidemiology and director of the Institute for Molecular Medicine Finland FIMM, has spent his entire career working on twin cohorts, both accumulating them and using them in research. 

Using the cohort studies, Kaprio has established that genetic factors underlie susceptibility for several diseases. For instance, diabetes, multiple sclerosis, Parkinson's disease and strokes all have a component that is at least partially hereditary.

In his most cited article from 2000, Kaprio combined the twin data from three Nordic cancer surveys and discovered that prostate cancer, colon cancer and breast cancer in particular all have a significant genetic component.

Kaprio has found that genetic variation also has an impact on the risk for lung cancer. Smoking itself is a major risk factor, but among people who smoke exactly the same amount, it is genetics that determines how the body reacts to the foreign compounds, removes them and repairs the resulting cell damage.

Twin cohort studies are important because they control for genetic variation. If identical twins have a higher likelihood for a specific characteristic or susceptibility for a particular disease than non-identical twins, this is a powerful indication that genetics is related to the issue.

Three of the most important cohorts are twins born before 1957, between 1975 and 79, and between 1983 and 86. These groups of twins have been interviewed at regular intervals. Some have also been asked to participate in clinical studies which have involved blood and gene samples.

These Finnish twin cohorts are exceptionally valuable. In Finland, the collection of older cohorts has also been handled well thanks to the efficient population register system. Finns are also a fairly genetically homogenous people. During the Stone Age, the population of Finland shrank to perhaps just a few thousand people. A particularly rare mutation that made its way to that historical bottleneck will have become quite common in the population, and therefore easy to monitor.

Roughly speaking, twin cohort studies have developed along the following lines. Previously, it was possible to use statistical methods to determine that many diseases and characteristics were dependent on genetics. Now, however, researchers have been able to pinpoint the exact genes and their effects.

Kaprio is one of the world’s foremost specialists in the genetics of addiction. From 2010 onwards, he has been discovering genes relating to tobacco addiction in particular.

In his recent study, based on full genome sequencing conducted among Finnish twin cohorts, Kaprio and his colleagues realised that 80% of the variation in the speed at which nicotine degrades in the body can be explained with genetic variation. They found hundreds of gene markers that influence this phenomenon, and 30% of the variation in the degradation rate could be attributed to the three most important markers in the regulatory sequence of the gene CYP2A6.

Based on this information, it will be possible to use gene markers to customise the correct dosage in nicotine-replacement therapy or the use of other types of treatments and drugs.

Jaakko Kaprio: Publications, Projects and Activities

Markus Perola (b.1966) is a research professor at the National Institute for Health and Welfare (THL), senior researcher at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) and visiting professor at the University of Tartu. His scientific career is characterised by simultaneous connections in many different directions.

Major health datasets received from different institutions - such as THL’s FINRISKI or FIMM’s genome surveys – have proven fertile ground for big data analyses both individually and combined. By data mining these resources, Perola has determined many factors relating to the causes and background of many non-contagious diseases.

Perola is constantly involved in major international consortia which consolidate data from several countries. This results in massive co-publications for scientific journals, with hundreds of authors.

For instance, it has been found that obesity is linked to 97 genes – and that most of them influence the brain. This supports the hypothesis that the cause of obesity lies not in the basic metabolism, but in the different reactions people have to their appetites and satiety.

Perola’s approach is based on systemic biology, i.e., the way everything impacts everything else. His work combines many of the trendy “omics”: genomics, epigenomics, transcriptomics, metabolomics and phenomics.

Perola’s most notable study to date has been the 2014 discovery that the amount of certain normal metabolic biomarkers in the blood could be used to determine an individual’s risk of dying from an illness within five years. Perola was interviewed extensively, even by CNN. The markers probably indicate general unwellness in the body.

Perola has also found that while women undergo a shift in their lipid metabolism which increases the ratio of “bad" cholesterol to “good" cholesterol and can render them susceptible to atherosclerosis at menopause, meaning around the age of 50, men can experience this as young as in their 30s.

Perola first studied to become a physician, but at his summer job as a pathologist's assistant at the Department of Forensic Medicine he was sent to Professor Leena Palotie’s laboratory to study gene technology, and was swept up by the research.

After completing a doctoral dissertation in genetics, Perola spent a year specialising in internal medicine, until Palotie lured him to become a postdoctoral researcher in Professor Kenneth Lange's research group in California to develop tools for analysing genetic data.

In 2001, Perola returned to Finland and began his work at THL and FIMM. In addition to his research career, Perola takes a night shift a few times a month at the Haartman Hospital, working on internal medicine emergencies as a “hobby” and to stay in touch with clinical medical work.

Markus Perola: publications, projects, activities

Tiinamaija Tuomi (b. 1963), docent of internal medicine, has built her research career around diabetes.

While working as a postdoctoral researcher in Melbourne in 1993, Tuomi and her colleagues found that approximately 10% of diabetics experience symptoms which place them somewhere in between type 1 and type 2 diabetes. The syndrome was termed LADA (latent autoimmune diabetes in adults) and is also known as type 1.5 diabetes.

Like type 2 diabetics, LADA patients only become diabetic in adulthood and do not require insulin treatment at the onset of the disease. On the other hand, the disease process is the same as with type 1 diabetes: the body’s autoimmune system attacks the insulin-producing cells in the pancreas and destroys them. However, the rate of destruction is much slower than in type 1 diabetes.

Through her genetic research, Tuomi later discovered that LADA diabetics have a fairly even spread of risk genes associated with both type 1 and type 2 diabetes, and it can be considered a genuine hybrid.

Tuomi is the joint head of the Botnia family study, based mainly in the Ostrobothnia region of Finland, which has tracked type 2 diabetics and their healthy family members since 1990 to determine how genes and lifestyle impact the development of diabetes. The study has involved approximately 15,000 people, and it has garnered many interesting results, particularly after 2005.

Tuomi has participated in several major gene screenings and has been involved with the discovery of the one hundred most common risk gene types associated with the development of type 2 diabetes. A larger group of risk genes means a larger probability that the individual will become diabetic, but lifestyle is also significant.

Tuomi and her colleagues recently discovered a gene variant in Ostrobothnia which seems to shield its carrier from diabetes.

Tuomi’s primary long-term occupation is being in charge of the treatment of diabetics at the Helsinki University Hospital's Endocrinology Outpatient Clinic. She conducts scientific research alongside her work, a few days a week.

Tiinamaija Tuomi: Publications, projects and activities

Jaakko Tuomilehto (b. 1946), professor emeritus of public health, led the research team that was the first in the world to establish in a rigorous, controlled study that type 2 diabetes is preventable through lifestyle choices. The study, published in 2001, has been cited more than 4,000 times. Before that, type 2 diabetes was commonly thought to be largely hereditary and difficult to prevent.

During his long career, Tuomilehto has in many contexts proven that lifestyle – exercise, smoking, obesity as well as alcohol, fat and salt intake - makes a difference. Today, these discoveries have become mainstream and have given rise to the current care recommendations.

In the mid-1980s, Tuomilehto and his research group established that treatment of high blood pressure among people of more than 60 years of age is still sensible, and in 2008, he made the same discovery among patients more than 80 years of age.

Thanks to Tuomilehto’s research in the 1980s, we now know that when treating blood pressure, the key is to prevent systolic pressure from getting too high. Before this, it was mistakenly thought that an increase in diastolic pressure was more dangerous.

Tuomilehto launched his career in the 1970s, studying blood pressure in the famous North Karelia Project, which was the first ever population-level health care project aiming to prevent chronic diseases. The most significant publications from the project were released at the beginning of the 1980s, but the project left Tuomilehto with the enthusiasm and data to launch a variety of follow-up studies relating to the prevention of diabetes.

At the turn of the new millennium, Tuomilehto and his research group drafted the much used and much cited diagnostic criteria which are used when diagnosing diabetes from high blood sugar in Europe (DECODE) and Asia (DECODA). The research data indicated that asymptomatic high blood sugar is related to cardiovascular disease and increased mortality regardless of diabetes.

In the first Finnish full-genome sequencing in 2007, Tuomilehto's group found genes that increase susceptibility to diabetes. At that point, it was possible to confirm that at least ten different gene loci were involved in type 2 diabetes.

Later, Tuomilehto has been involved in international joint analyses, and now approximately 100 gene loci are known to increase susceptibility for diabetes. Many of them have little impact if present individually.

During the past few years, Tuomilehto and his research group have proven that the same risk factors underlie Alzheimer’s disease and cardiovascular disease. This means that a healthy lifestyle can also help your memory.

Jaakko Tuomilehto: Publications, projects and activities