New Drugs for Heart Diseases
The human heart beats approximately 100,000 times every day. Pumping oxygen-rich blood across our body, the heart is essential in keeping our other organs healthy. A heart attack occurs when cardiac cells, including the beating heart muscle cells (cardiomyocytes) are themselves deprived of oxygen due to a blockage in a blood vessel in the heart. This in turn leads to the death of these cells which are incapable of regrowing, and therefore reduces the heart’s pumping capacity. This phenomenon is known as heart failure. Similarly, high blood pressure or genetic conditions can cause the heart muscle to stiffen or enlarge, decreasing the heart’s ability to pump blood.
We aim to address some of the fundamental questions pertaining to heart diseases. One of our goals is to identify ways to force remaining heart muscle cells to regrow (proliferate) to heal the heart after a heart attack. Stem cells are excellent tools for such studies as they can become any cell type of the human body. In our lab, we generate heart muscle cells and blood vessel endothelial cells from stem cells and study the effects of different conditions, drugs, or chemical compounds on these cells.
Learn more about Dr Qasim Majid and Dr Virpi Talman from the Regenerative Cardiac Pharmacology lab.
Fluorescence microscope images of:
- Human pluripotent stem cell-derived cardiomyocytes.
- Human pluripotent stem cell-derived cardiomyocytes and endothelial cells.
Prof. Yliperttula leads the multidisciplinary and multinational Biopharmaceutics research group at the University of Helsinki’s Faculty of Pharmacy.
The research program consists of the development of biomaterials for cell culture, drug delivery, and tissue repair together with detection technology. The developed biomaterials are based on nanofibrillated cellulose, nanoparticles, and extracellular vesicles.
Two of the most important projects on-going in the Biopharmacy research group are:
- EV Ecosystem: https://www.bloodservice.fi/Research%20Projects/ev-ecosystem
- GeneCellNano Flagship: https://www.genecellnano.fi
Nanofibrillated cellulose in skin graft donor site treatment (FibDex)
A.Detachment of dressing from donor site. without breaking the newly formed skin.
B.The epithelialised skin without scar formation.
In vitro and in vivo enhanced antitumor effects of oncolytic virus and paclitaxel encapsulated in extracellular vesicles (EVs).
A.Lung cancer cells were implanted subcutaneously into mice and EV formulations were administered intravenously (i.v.). Tumor growth was followed over time.
B.Kaplan-Meier test was used to calculate the survival profile.
Funding sources: BioCenter Finland, Tekes-The Finnish Funding Agency for Technology and Innovation, EU-FP7 (LIV-ES project, HEALTH-F5-2008-223317), Graduate School of Pharmaceutical Sciences, Finnish Red Cross Service, MATRENA graduate schools, Academy of Finland and EU-Erasmus Exchange Student Exchange Programme, UPM-GrowDexI I –III projects, UPM-Wound project, Huttunen foundation, professor-pool Orion foundation
Light triggered drug release
A central theme in pharmaceutical research is controlling drug release. A particular area of interest for us is light-triggered release from nanosized drug carriers. We consider light to be the most flexible drug-release trigger for advanced drug delivery systems. Light can be used to both trigger and subsequently control the drug release with extreme time and location precision. To have the best tissue penetration, we are focusing on red-light activatable nanocarriers. Modern ultrathin light guides also enable the treatment of deeper tissues with minimal surgery.
A formidable physiological barrier to light-triggered drug release has been the inability to use high-energy blue/UV light as the triggering signal, making deeper targets within tissues accessible only to red light. However, red light, with its intrinsically lower energy, has limited value in photochemical reactions because e.g., the photocleavage of covalent bonds typically requires UV-light. In order to circumvent this issue, we focus on converting red light into blue light in precisely-tailored drug-releasing implants.
Learn more about Prof. Timo Laaksonen and Dr Tatu Lajunen from the Pharmaceutical Nanotechnology Lab.
After we take a drug, it will travel around the body in our blood, entering the cells of our different tissues, such as the liver. This movement can be helped, or hindered, by certain transport proteins. These transporters act like pumps on the cell membrane, protecting the cells from toxic compounds or bringing them essential nutrients. Their function can differ between individuals due to differences in genetics. Some drugs or dietary compounds may also alter their function. These changes can possibly affect the efficacy of drug treatment.
In our laboratory, we grow cells of human and animal origin and use them to study the function of transporters. When information about the function of a transporter is added to a computational model, we can predict its effect on drug treatment. In this way, we aim to ensure safe and effective drug treatments.
We have for instance studied how certain natural products and food additives can affect the function of transporters on a cellular level. Based on our results, we suspect that certain colourants, such as curcumin, may affect the absorption of drugs from the intestine. We have also studied the effect of genetic alterations on the function of several transporters. Many genetic alterations significantly decrease the function of transporters in cell studies, suggesting that drug levels in the body may be different in people with these alterations.
Learn more about Dr Eva Ramsay from Professor Heidi Kidron’s Transporter group.
- Graphic of a transport protein in the cell membrane, pumping drugs out of the cell and into the blood.
- Immunofluorescent microscope image of transporter proteins (green) on the surface of cells. The nucleus, where genetic information is stored, is in blue.
Regenerative Neuroscience: Developing Regenerative Treatments for Incurable Diseases
The number of patients with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple sclerosis (MS) increases with age. There is no treatment that either prevents these diseases from progressing or repairs the damage to the nerve cells.
The Regenerative Neuroscience lab is researching and developing new drug candidates for ALS, PD, and MS that prevent the disease from progressing and repair nerve cell damage. We use several different research models, such as stem cells, as well as various genetic and toxin-generated disease models. The goal of our research is to ascertain the most promising drug candidates and assess these in clinical trials for the benefit of patients.
Learn more about Tapani Koppinen and Aastha Singh from Professor Merja Voutilainen’s Regenerative Neuroscience Lab.
Graphical illustration of:
- Amyotrophic lateral sclerosis
- Parkinson’s Disease
- Multiple sclerosis
- Modelling brain cell damage in brain slice cultures and searching for new therapies
The Good Side of a Virus
Our research group develops vaccines against cancer. How do we do that? We modify viruses to seek and specifically destroy cancer cells whilst leaving live, healthy cells undamaged. During this process, we reprogram the immune system to store important information about the cancer to prevent it from emerging in the future. These special viruses are called oncolytic viruses and once combined with special features present in the tumour, they present a lethal strategy to destroy cancer. They work like a vaccine, teaching our bodies how to recognise emerging tumours as external intruders in advance of them becoming established, life-threatening cancers.
Learn more about Manlio Fusciello from Professor Vincenzo Cerullo ImmunoViroTherapy lab.
The physiology underlying the effects of ketamine, psychedelics, laughing gas, and other rapid-acting antidepressants .
Depression is ever more common despite the growing investments in mental health care and the use of antidepressants. Conventional antidepressants alleviate the symptoms only after weeks of continuous use, and a third of patients do not benefit from them, although most suffer side effects. Thus, there is a large clinical demand for better treatments. However, to design new treatments, it is crucial to first understand how antidepressants work. 70 years since their discovery, there is still no verdict on how antidepressants alleviate the symptoms of depression.
However, in contrast to conventional antidepressants, treatments like ketamine, psychedelics, nitrous oxide, electroconvulsive therapy, and sleep deprivation act within hours of a single treatment, with effects lasting up to weeks. As ketamine and laughing gas are removed from the body rapidly after administration, and electroconvulsive therapy and sleep deprivation are physiological in nature, it appears that the therapeutic response arises from the brain itself.
Our research has uncovered a mechanism through which exposure to the brief treatment boosts brain plasticity and alleviates depressive symptoms. The mechanism is connected to the intrinsic regulation of sleep, energy, and metabolism. By understanding this phenomenon better, we may finally unravel how antidepressants work, opening new avenues for the development of more effective and better-tolerated treatments.
Learn more about Okko Alitalo from the Laboratory of Neurotherapeutics.
- Summary of our research.
- Thermal camera portrait after a long day of experiments.
- Distribution of glucose in brains after laughing gas or medetomidine and thermal images of mice after laughing gas treatment.
Cross the cell membrane barrier: How smart polymers transfer therapeutics into cells
All of the cells in our body are covered by protective membranes that prevent invasions from bacteria and viruses. The cell membrane does not allow big molecules, such as proteins or RNA, to enter freely into cells.
Advances in modern medicine have seen the advent of advanced therapies such as gene therapy for the potential treatment of previously incurable genetic diseases. Further, mRNA vaccines against SARS-CoV-2, the virus responsible for the COVID-19 pandemic, have been developed as well as cell therapies for cancer treatment. All these treatments rely on the successful delivery of big therapeutic molecules into cells.
My research focuses on the development of smart polymer materials that function as delivery “vehicles”, that help therapeutic molecules cross the cell membrane barrier. I also use different techniques, trying to understand how these drug delivery “vehicles” interact with cells and transport within different compartments in the cell.
Learn more about Dr Shiqi Wang and the Nanomedicines and Biomedical Engineering Lab.
- Illustration of how smart polymers transfer therapeutics across the cell membrane by “hijacking” the natural intracellular vesicles.
- Transmission electronic microscopy image of cell nuclei and natural intracellular vesicles.
Secrets of household items revealed by coherent Raman microscopy
This project is a part of the Quantitative Chemically-Specific Imaging (qCSI) Infrastructure for Material and Life Sciences, which offers highly advanced imaging technologies for industrial and academic use, in Jyväskylä, Lappeenranta, and Helsinki campuses. In Helsinki, we have constructed a microscope unique to the Nordic countries.
Unlike common light microscopy, our instrument uses so-called coherent Raman spectroscopy, which allows us to visualise the invisible infrared appearance of the sample. The infrared is a much broader and more information-rich spectral region than compared to the visible region we see with our eyes, therefore permitting chemically highly specific imaging.
Learn more about Dr Teemu Tomberg from the Pharmaceutical Spectroscopy and Imaging group.
- Coherent Raman Microscope.
- Melatonin tablet as viewed under this microscope. Melatonin active ingredient, Magenta; bulking agents/stabilisers, green, cyan.
- Body Lotion as viewed under this microscope. Minor oily components form droplets in the surrounding water.
In Search for Novel Antibacterials
Bacteria are single-celled ancient creatures that are invisible to the human eye due to their small size. Nonetheless, millions of them surround us and inhabit our bodies in the same way that humans inhabit planet Earth. They are an integral part of human health, performing many important tasks such as aiding the digestion of food and processing nutrients. They also generate vitamins and form a protective layer on our skin.
On the other hand, harmful bacteria can cause serious diseases. Antibiotic overuse over the last 80 years has resulted in the rapid emergence and spread of harmful, antibiotic-resistant bacteria, making common infections difficult, if not impossible, to treat. New bacteria-eliminating drugs and treatment methods are desperately needed.
The Bioactivity Screening group at the University of Helsinki’s Faculty of Pharmacy employs high throughput screening to aid the discovery of antimicrobial drugs. We can test thousands of chemical compounds and natural products for their capacity to kill bacteria within days using multi-well plates and laboratory automation. In our lab, we also develop research tools. For example, the co-culture of bacterial and mammalian cells allows us to model the infection process and test novel ways to prevent infections.
Learn more about Dr Polina Ilina from Professor Päivi Tammela’s bioactivity screening group.
- Adding compounds to a 96 multi-well plate using a multi-channel pipette.
- Agar plates containing bacterial cells.
Hidden Treasures: From Natural Products to Medicines
A natural product can be defined as a plant, an animal, or a microorganism, that has not been subjected to any treatment other than drying or other such preservation processes. A natural product can also be a part of an organism, for example, a leaf of a plant or an isolated organ of an animal.
Compounds derived from natural products can be obtained by extraction, followed by isolation and purification procedures. Isolated pure compounds are further tested for bioactivity by various methods. Many of the natural compounds are isolated, purified, and compounded directly into tablets or injectables. Drugs can also be based on derivatives of natural products where the chemical structure has been modified to obtain the desired medicinal properties.
For centuries, natural products were the only available form of drugs. Among modern drugs, about 40% are of natural origin with some therapeutic areas seeing higher use of natural drugs. Approximately 60% of anticancer drugs and 75% of drugs against infectious diseases are either natural products or derivatives of natural products.
At the University of Helsinki’s Faculty of Pharmacy, Prof. Tammela’s group studies various natural products for their chemical composition and bioactivity. One study area is the Chaga mushroom which is used in folk medicine for the treatment of cancer and gastric disorders. In the Bioactivity Screening lab, the Chaga mushroom is tested for its anti-herpes simplex virus ability.
Learn more about Dr Karmen Kapp from Professor Päivi Tammela’s bioactivity screening group.
- Chaga mushrooms in the forest.
- Extraction of natural products.
- Analysis of products.
The Medicinal Chemistry Lab designs, discovers, chemically synthesises, characterises, and optimises biologically active compounds.
Inspiration for the drug molecules can come from nature (plants, microorganisms, and marine compounds), computational molecular modelling, or repurposing previously known compounds.
Drug molecules are synthesised in the laboratory, purified, and then characterised. They are subsequently subjected to biological activity assays and the resulting biological activity information is used to optimise the compound further. We are synthesising small-molecule libraries of novel antibacterial, anticancer, antiviral, antiparkinsonian, and heart regenerating compounds. We are also developing green and sustainable methods to prepare the drug molecules.
Learn more about Dr Paula Kiuru from Prof. Jari Yli-Kauhaluoma’s Medicinal Chemistry lab.
- Identification of active compounds from nature.
- Computational design of new drugs.
- Synthesis of a new compound in the laboratory.
Neuroprotection and Brain Repair
The brain is a complex structure that consists of various cell types like nerve cells (neurons) and supporting brain cells (glia). Our lab is interested in brain protection and repair processes thus; our research focuses on diseases like Parkinson’s disease and stroke. The central feature of neurodegeneration is a failure of proteins functioning correctly. Appropriate protein function is dependent upon the correct 3D protein structure. If this structure is disordered, the consequences for brain cells are often pathological. The problems in protein structure can act as a seed in the development of large aggregates and initiate disease progression, particularly in aged brains. Protein aggregates can be found in several neurodegenerative diseases and can be found within various compartments of a cell. We are also interested in the glia component of brain diseases. About half of the cells in the brain are cells other than the neurons. These are predominantly glial cells. A subset of these, the microglial cells, are small but mighty cells that allow the brain circuits to function correctly. They also mediate inflammation in the brain, which is a significant cause of pathology in many brain diseases. There are many aspects in glial cell biology that are still unknown, and it is likely future drugs will target these glial cells to treat neurodegenerative diseases.
Learn more about Prof. Mikko Airavaara and Safak Er from Professor Mikko Airavaara’s Neuroprotection and Neurorepair lab.
Immunofluorescent microscopy images of:
- Dopamine neurone