2 June 2023
M.Sc. Karina Barreiro's thesis focused on describing best practices for transcriptomic studies of extracellular vesicles found in urine (uEV) and to discovering transcriptomic biomarkers in uEV for early detection of diabetic kidney disease and stratification of individuals with risk of diabetic kidney disease progression.
The results showed that the uEV transcriptome is indeed a source of promising non-invasive kidney disease biomarkers with potential prognostic value. However, rigorous assessment of pre-analytical variables and guidelines on best practices are a must not only for generating reliable and replicable results but also to understand the limitations when comparing uEV studies.
The thesis was supervised by Professor Harry Holthöfer and Dr. Maija Puhka.
7 October 2022
M.Sc. Sanni Ruotsalainen's thesis focused on improving understanding of the genetic background of coronary artery disease (CAD) and its risk factors as well as improving the risk estimation for CAD 1) by developing statistical methods and tools used in multivariate genetic analysis of biomarkers, 2) by expanding the traditionally used biomarker set for coronary artery disease, 3) by studying an isolated population to identify high-impact variants either very rare or absent in other populations and 4) by identifying individuals in high- risk for CAD using both traditional and genetic risk factors.
The thesis was supervised by Prof. Samuli Ripatti and Dr. Ida Surakka.
14 February 2022
LL Elmo Saarentaus's thesis focused on investigating and comparing the contribution of rare and common genetic variance to complex traits. The studies of this thesis highlight distinct features of both rare and common variation and challenge the single gene hypothesis for complex traits.
The thesis was supervised by Aarno Palotie, Olli Pietiläinen and Mitja Kurki.
February 7, 2022
Image-based tissue phenotyping has been commonly used for histological classification. It also allows the direct visualization of the distribution and expression of functional molecules. In this thesis, Jie Bao developed a spatial image analysis tool package (Spa-RQ) and applied these tools to discover spatial phenotypic features in non-small cell lung cancer histotypes, contributing to understanding the heterogeneous nature of tumorigenesis, cancer progression, and drug sensitivities.
The thesis was supervised by Dr. Emmy Verschuren and Dr. Peter Horvath.
November 29, 2021
Functional profiling of tumor cells collected from cancer patients has the potential to tailor individualized cancer treatments. In this thesis, the translational potential of this strategy for non-small cell lung cancer was examined. Drug sensitivity and resistance testing were conducted using tumor-derived fresh uncultured or cultured cells from mouse models and clinical samples. The results demonstrate the clinical feasibility and utility of tumor-derived fresh uncultured or cultured cells for pharmacological research and for identifying individualized cancer treatments.
The thesis was supervised by Dr. Emmy Verschuren and Professor Krister Wennerberg.
Associations with childhood aggressive behavior using multiple raters : co-occurrence, antisocial personality disorder prediction, and biomarkers
October 15, 2021
In her thesis, Alice Whipp aimed to improve our understanding of aggressive behavior in childhood and adolescence by looking at the following aspects: co-occurring behaviors/problems, differences between raters, aggression subtypes, adolescent aggression as a predictor of a young adult personality disorder, and biomarkers of aggression.
The findings help to clarify the co-occurrence of aggressive behavior with other behaviors across raters and countries, to show how common the co-occurrence is and that it should be taken into consideration when studying aggressive behavior, including from (epi)genetic or biological perspectives. Her thesis provides refinements to the aggressive behavior phenotype, new avenues for aggression biology investigations, and ideas for where to improve or personalize treatment options.
The thesis was supervised by Docent Tellervo Korhonen and Academy Research Fellow Eero Vuoksimaa.
Targeting STAT3 and kinases in lymphoid malignancies
May 27, 2021
Elina Parri’s thesis focused on a molecule called STAT3. In cancers, activation of the STAT3 is associated with enhanced cellular transformation, increased metastasis and drug resistance. Direct therapeutic targeting of STAT3 has proven to be challenging and only a few direct STAT3 inhibitors have entered early phase clinical trials. The thesis used high-throughput screening applications for identifying novel strategies for indirect STAT3 targeting. The results suggest novel drug combinations for targeting malignant NK-cells.
The thesis was supervised by Professor Krister Wennerberg.
Functional molecular precision medicine for acute myeloid leukemia
February 5, 2021
In Disha Malani's thesis, a real-time precision systems medicine strategy was applied to identify targeted therapeutic options and biomarker associations in 252 samples from 186 acute myeloid leukemia patients. The integration of molecular profiling and drug sensitivity and resistance testing data revealed drug efficacies and underlying mutations and gene expression biomarkers for a subset of patient samples.
The results suggest that functional precision medicine could have clinical utility, although it needs supportive evidence from formal prospective clinical trials. The thesis highlighted novel avenues to define therapeutic opportunities for specific molecular subgroups of adult acute myeloid leukemia.
The thesis was supervised by Professor Olli Kallioniemi.
Fine-scale genetic structure and polygenic scores in Finland
January 29, 2021
Sini Kerminen's doctoral thesis examined the fine-scale genetic structure and its role in the geographic distribution of polygenic scores in Finland.
The first part of the thesis expanded the understanding of the genetic structure of Finland by determining the geographic border for the major genetic split between East and West Finland, and by identifying 17 previously unreported genetic fine-scale populations. The second part of the thesis utilized the earlier results by building, based on the fine-scale genetic structure, reference groups to estimate the genetic ancestry profile of an individual within Finland. he third part of the thesis assessed the role of the genetic split between East and West in the geographic distribution of the genetic risk of five complex diseases (coronary artery disease, rheumatoid arthritis, schizophrenia, ulcerative colitis, and Crohn’s disease) and three quantitative traits (height, body mass index, and waist-hip ratio) using polygenic scores.
The thesis was supervised by Dr. Matti Pirinen and Professor Samuli Ripatti.
The DISC1 gene network in major mental illnesses in Finland
17 December, 2020
Vishal Sinha's thesis focused on studying the impact of the DISC1 gene network on the aetiology of schizophrenia and other major mental illnesses in Finland.
In his thesis, Vishal performed comprehensive studies of 8 Finnish cohorts and identified functional variants within the PDE4D, NDE1, and the DISC1 gene increasing susceptibility to schizophrenia.
The thesis was supervised by Dr. William Hennah.
Polygenic contributions to dyslipidemias and related cardiometabolic diseases
September 17, 2020
Pietari Ripatti's thesis focused on answering fundamental questions about the genetic architecture of common cardiometabolic diseases, and about the impact of genomic risk measurements on disease incidence prediction.
In his thesis, Pietari first showed that the most common familial dyslipidemia traditionally considered monogenic, FHC, is mainly polygenic. Second, he found that polygenic hyperlipidemias considerably increase lipid levels as well as CAD risk. Finally, polygenic risk scores were demonstrated to predict future disease onset better than current clinical risk scores alone.
The thesis was supervised by Professor Samuli Ripatti.
Point-of-care diagnostics with digital microscopy and artificial intelligence
September 4, 2020
In his doctoral thesis, Oscar Holmström described, developed, implemented and evaluated novel diagnostic solutions to digitize microscopy samples at the point of care for analysis either visually or with automatized digital algorithms. This topic has enormous global health implications, since the lack of access to diagnostics is an enormous problem which causes underdiagnosis of various common and treatable diseases.
Oscar's thesis was supervised by FIMM Research Director Johan Lundin and Dr. Nina Linder.
In search of perinatal correlates of left-handedness
August 21, 2020
The known bias in human hand usage is fascinating, but the origins of handedness remain largely unknown, with about 10% of people being left-handed. Studies however point to early development in handedness formation. The main aim of Kauko Heikkilä's thesis work was to study whether perinatal covariates have an association with left-handedness.
The thesis was supervised by late Professor Emeritus Matti Iivanainen, Eero Vuoksimaa, Jari Haukka and Aulikki Saari-Kemppainen.
Computational frameworks to aid pharmacological studies: Tools, Databases and Prediction models
28th February 2020
The accumulation of large-scale drug molecule profiling datasets has paved the way to a new field of science, called chemoinformatics. Developed in silico models can serve as an efficient and cost-effective augmentation to the experimental laboratory screening approaches. The main aim of Balaguru Ravikumar's thesis was to develop novel computational methods, databases and tools for interpreting drug screening data.
The thesis work was supervised by Professor Tero Aittokallio.
Epigenetic Profiling of Obesity and Smoking
March 27th, 2020
Sailalitha Bollepalli's thesis work focused on elucidating the role of epigenetic and transcriptomic markers in obesity and smoking. Her main aim was to identify weight-loss and smoking-associated signals by integrating these different types of genome-wide omics datasets by various statistical approaches and bioinformatics tools.
The thesis was supervised by Dr. Miina Ollikainen and Professor Jaakko Kaprio.