The University of Helsinki’s most cited researchers in the fields of geosciences and pharmacology.
Highly cited researchers: geosciences and pharmacology
Markku Kulmala (b. 1958), professor of physics, has been the world's most cited geoscientist since 1 May 2011. He has reached this position thanks to his groundbreaking research on the formation of small particles in the atmosphere as well as on the interaction between the climate and forests. Kulmala has developed completely new hypotheses, provided evidence for them and built a research infrastructure around them, the most central components of which are the SMEAR I and II stations in Värriö and Hyytiälä respectively, both established in the 1990s.
At the turn of the millennium, Kulmala first formulated the hypothesis that the atmosphere must contain molecule clusters and particles of 1—3 nanometers in diameter. He then proved their existence as well as the fact that they largely consist of organic by-products of photosynthesis.
The forests of the world produce such aerosols, which serve as condensation nuclei for droplets and contribute to the creation of clouds. The clouds then reflect sunlight back into space, thus cooling the climate.
These phenomena form the foundation of Kulmala’s hypothesis regarding the feedback mechanism between climate change and forests – namely, that forests slow down climate change. The studies conducted at the SMEAR II station have proven his hypothesis to be correct.
In the feedback mechanism, photosynthesis increases when the amount of carbon dioxide in the atmosphere increases. Photosynthesis creates hydrocarbons as by-products, which then react in the atmosphere, forming fairly stable aerosol particles. These particles serve as condensation nuclei for clouds, which refract sunlight back into space.
As the amount of aerosol particles increases, the refraction becomes more intense in the lower atmosphere. As a result, pine needles located under the tops of coniferous trees receive more photons, which enables them to photosynthesise even more, which binds even more carbon dioxide from the atmosphere, generating even more aerosol particles.
During the past few years, Kulmala has focused on the connections between air quality and climate change as well as potential solutions to improve the air quality in China.
Kulmala and his wife are part of a peer support network for couples and families through the NGO Parempi avioliitto.
Tuukka Petäjä (b. 1975), professor of physics, is a highly cited researcher, particularly as a developer of measuring equipment and methods. For example, he has carried out mass spectrometer measurements of atmospheric sulphuric acid at the SMEAR II station at Hyytiälä.
Thanks to Petäjä’s work, the measuring equipment at Hyytiälä has become more sophisticated, and the range of measurements available has expanded. The founding principle is that measurements are taken 24 hours a day, throughout the year. In addition to continuous measurements, Petäjä has coordinated intensive measuring campaigns where tools which supplement the measurement capacity have been brought to Hyytiälä by the research groups working with them. The most significant such visit was the eight-month measuring campaign undertaken by the mobile laboratory funded by the US Department of Energy at Hyytiälä in 2014.
In recent years, a great deal of groundbreaking research on the interaction between the atmosphere and forests has been conducted at Hyytiälä. The research has indicated that the organic vapours emitted by trees participate in the clustering and growth of small aerosol particles. Ultimately, the cluster grows to a large enough size to enable a cloud droplet to form around it. The clouds and aerosol particles then refract sunlight back into space, which cools down the climate.
Climate change influences the way forests grow, but at the same time, the aerosol particles generated in forests influence the climate. Research into this feedback mechanism has been active at Hyytiälä during the past few years.
Petäjä became interested in the climate effects of aerosols already as a student of physics, and he developed his first aerosol measurement device in his Master's thesis. In 2007-2008, he worked as a postdoctoral researcher at the National Center for Atmospheric Research in the USA, where he became profoundly familiar with mass spectrometer methods of measuring sulfuric acid and hydroxyl radicals in the atmosphere.
In 2008, he brought this competence to the University of Helsinki to serve its SMEAR II station.
Petäjä is in charge of the development of aerosol particle–measuring equipment at the Division of Atmospheric Sciences of the Department of Physics. Thanks to laboratory tests and long-term measurements conducted all over the world, it is now possible to understand step by step on a molecular level how aerosols join together to form new particles and thus impact the world’s radiation balance and climate change.
Janne Backman (b. 1968), professor of clinical pharmacology and personalised medicine, has studied the interactions between drugs and looked into the molecular mechanisms that cause them. His discoveries have often also helped develop research methods for such interactions. Backman has also done extensive research on how other individual factors impact drug treatment.
In the 1990s, the scientific community was becoming aware of the fact that many drugs, such as the sedative midazolam, are broken down in the liver with the help of the CYP3A4 enzyme, and that certain drugs interfere with the normal function of this enzyme - either blocking or accelerating it.
In his dissertation in 1995, Backman studied how different drugs influence midazolam concentrations when used concurrently. To determine the concentration levels, Backman took blood tests, but also studied the effect of the sedative on the patients, for example, measuring their eye movements to determine their reaction speed.
It is now known that up to half of all drugs are metabolised with the CYP3A4 enzyme. Based on Backman’s discoveries, the pharmaceutical industry now commonly uses midazolam as a model substance in tests to see whether a new drug interferes with the CYP3A4 metabolism.
After completing his dissertation, Backman spent more than a year as a postdoctoral researcher in Stuttgart with the intention of focusing on research into the targeted drug delivery systems for cancer that were being developed. The ambitious projects were unfortunately bogged down by methodological challenges, and the biggest discovery Backman made in Germany came from a side project.
Backman took part in a research project that was among the first to establish that levels of the cyclooxygenase-2 enzyme were elevated in infected joint tissues. The discovery made sense and explained the efficacy of COX2-selective anti-inflammatory painkillers, which were still under development at the time.
In 1998, Backman returned to Professor Pertti Neuvonen’s famous group to scrutinise drug-drug interactions.
At the turn of the millennium, they discovered that two cholesterol medications, cerivastatin and gemfibrozil, caused muscle damage when used simultaneously. The muscle damage caused by cerivastatin ultimately led to approximately 100 deaths worldwide, and the drug was consequently pulled from the market in 2001.
In a clinical study published in 2002, Backman and his colleagues proved that gemfibrozil caused the levels of cerivastatin in the bloodstream to elevate sixfold, or even tenfold in some cases, which was responsible for the high risk of muscle damage.
Backman began to trace the exact biochemical mechanism underlying this interaction, but American researchers got there first, demonstrating how gemfibrozil blocks the cerivastatin-metabolising CYP2C8 enzyme through a complex process.
However, his study of this matter later led Backman to make many juicy discoveries about significant drug interactions. Often the underlying mechanism has been that the function of the enzymes breaking down the drug has for some reason become disrupted.
Pertti Neuvonen (b. 1943), professor emeritus of clinical pharmacology, has studied drug interactions since the late 1960s and continues to work at Biomedicum despite being nominally retired. Neuvonen ranks as 52nd in the global citation ranking of drug researchers (pharmacology and toxicology).
In his research, Neuvonen divides drugs into “villains" and "victims". The villains change the behaviour of the victim drugs by heightening their potency to a dangerous degree or completely blocking them, even in cases where the two drugs would be perfectly safe and effective if taken separately.
Many of Neuvonen's studies have been sparked by his doctor colleagues consulting him on a strange patient case. To determine the reasons for the cases, Neuvonen and his group have undertaken special investigations.
For example, Neuvonen was once contacted by a dermatologist whose patient had used a calcium blocker to lower blood pressure without complications, but once the patient was prescribed an anti-fungal drug, his legs became very swollen up to the knees.
The patient agreed to undergo further testing. He first took the calcium blocker without the anti-fungal drug and then with it, which triggered a tenfold increase in the amount of the blocker in his blood. After this, the interaction of the drugs was confirmed with a control group of healthy volunteers.
Neuvonen and his group have used similar methods to identify several villain and victim drugs from among commonly used medications.
Statins used to control cholesterol, short-acting sleeping pills, certain allergy and asthma medications as well as several diabetes, heart and pain medications have been identified as victims.
Meanwhile, some anti-fungal medications, antibiotics, psychiatric medications and hypolipidemic drugs have been found to be villains. The interactions between these drugs may be lethal.
The results of Neuvonen’s group often have an immediate impact on drug treatment. Through the study of the mechanisms and rules of drug interactions, the researchers have prevented adverse effects and improved treatment results. Many of the group’s discoveries are now found in textbooks, but the original research is rarely cited.
Together with his colleagues, Neuvonen has also worked to improve drug safety on a more general level by seeking to determine the significance of the patient’s age, genetics and additional illnesses on drug interactions and improving the treatment of poisoning victims.
During his career, Neuvonen has occasionally quarrelled with the pharmaceutical industry, as companies have initially sought to deny his research results. However, Neuvonen still views drug development positively and considers it important. Drug safety has improved in leaps and bounds during his career, both in Finland and elsewhere.
Jaakko Kangasjärvi (b. 1960), professor of plant biology, has built his career around reactive oxygen species (ROS), such as hydroxyl radicals and hydrogen peroxide. Kangasjärvi was among the first scholars to establish that ROS compounds are also beneficial to plant cells in transmitting signals. He is ranked as the 13th most cited among the world's botanists and zoologists.
ROS compounds have traditionally been thought to be unfortunate by-products of energy production, harmful to cells which must neutralise them with antioxidants.
At the beginning of his career in the 1990s, Kangasjärvi’s research group studied the harmful effects of ozone on plants. The leaves of birch trees, for example, begin to die when the air has a high concentration of ozone. This damage was thought to be physical in nature.
The truth, however, proved to be more complex. Kangasjärvi discovered that the ROS compounds created when ozone degrades trigger a suicide mechanism in the plant cell. The plant cell interprets the presence of an ROS compound as a sign that pathogens are nearby. One form of defence against pathogens is that the cell destroys itself so that the pathogen cannot spread.
This means that ozone damage is the result of both gene function and metabolism - and that ROS compounds have a signalling function. After making this discovery, Kangasjärvi has focused on the many signalling functions and mechanisms of ROS compounds by studying the Arabidopsis, a common model plant in plant biology.
When plants are exposed to pathogenic microbes they begin to produce ROS compounds to signal that action is needed. Similarly, when plants are exposed to bright light after long periods in the shade they begin to produce ROS compounds, after which the plant is quick to adapt to its new circumstances.
During his career, Kangasjärvi has also conducted a great deal of genome sequencing, for example on the Populus trichocarpa, Arabidopsis and Petula bendula. Even though Kangasjärvi studies genes and molecular biology, his work has a basis in evolutionary biology, as he has been trying to determine what concrete benefit can particular gene functions yield to the plant as it strives to adapt to its environment.
Transporter proteins have lifted Mikko Niemi (b.1975), professor of pharmacogenetics, to the top of the list of Finland’s most-cited drug researchers. In his groundbreaking studies, Niemi has established that hereditary variations in transport proteins influence the ways drugs are absorbed, how they reach the right location in the cell and how they are excreted from the system.
Niemi completed his doctoral dissertation in the early 2000s under Professor Pertti Neuvonen’s supervision on the interactions between diabetes medications, specifically, how certain drugs interfere with the enzymes responsible for breaking down diabetes medications in the liver. Niemi observed significant differences in drug concentrations in healthy individuals and suspected genetics to be the cause. At the time, however, there was little competence in Finland to study such issues.
Genomics was trending at the time, and in 2003, Niemi left for Stuttgart's famous Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology to gain more experience in the field.
During his postdoctoral research, Niemi discovered that the genetic variation of the OATP1B1 transport protein influenced the concentration of the water-soluble cholesterol medication pravastatin. He also located a mutation which reduced the drug's access to the liver and its excretion from the system.
It was thought at the time that transport proteins were only significant in the flow of certain water-soluble drugs in the system, and that fat-soluble drugs – that is to say, most of them – could easily slip past the fatty acids of the cell membranes.
Niemi was sceptical of this hypothesis. After returning to Helsinki in 2004, he established his own research group, which made its breakthrough in 2006. Niemi and his colleagues discovered that the fat-soluble cholesterol drug simvastatin also required a transport protein and that a hereditary mutation in the OATP1B1 gene disrupted the flow of the fat-soluble simvastatin more than that of the water-soluble pravastatin.
This discovery shook the field of pharmacology. Niemi was invited to join an international consortium of academic and industrial researchers and pharmaceutical officials to consider the impact of transport proteins on drug development.
The report on the significance of transport proteins, published by the consortium in 2010, has been cited nearly a thousand times. It is currently routine in drug development to study how differences in transport proteins impact the flow of the drug in the system, and whether the new drug could interact with other drugs by preventing their transport.
The transport protein gene test, based on Niemi’s work, is in clinical use in several countries, and Niemi has himself participated in the international consortium drafting instructions for interpreting the results of the test.
Jouni Hirvonen (b. 1965), professor in pharmaceutical technology, has received a boost in his citation numbers from the research in silicon particles he began in 2003 in cooperation with the University of Turku.
Introducing a drug inside a porous silicon (PSi) structure is one of the most promising nanotechnology innovations in the field of pharmacy. Research on the topic became a global trend at the turn of the millennium, and Hirvonen and his colleagues have been at its forefront. No PSi drugs have yet reached the market.
Hirvonen's breakthrough study from 2005 describes how well PSi particles are suited for delivering hydrophobic drugs in particular. Most drugs are hydrophobic, which is to say that they are difficult to dissolve into water and thus have weak potency.
Hydrophobia is usually caused by the capacity of drug molecules to clump together into large water-resistant crystals. Hirvonen’s study established that once the drugs are packed into the 2-50–nanometre pores of PSi particles, they cannot crystallise and consequently dissolve better in the patient's system.
Together with his group, Hirvonen has since discovered how PSi particles can be coated using different materials. These coatings can slow down the dissolution of the drug to ensure a consistent drug release or to help deliver the drug to the desired target.
At the moment, Hirvonen’s group is studying how PSi particles can help patients suffering from heart failure or degenerative brain diseases.
At the beginning of his research career in the 1990s, Hirvonen worked as a doctoral student in Kuopio and a postdoctoral researcher in California, studying how electrical current can be used to push charged drug compounds through the skin.
Most drugs, peptides in particular, carry an electric charge. Hirvonen has participated in the development of medicinal patches with a low electric charge.
Hirvonen has a host of administrative responsibilities. He is a member of the board of the European Association of Faculties of Pharmacy as well as the European Directorate for the Quality of Medicines and Health Care. Hirvonen has been the dean of the Faculty of Pharmacy since 2010.