In this thesis work, M. Sc. Lea Urpa focused on the genetic architecture of intellectual disability in Northern Finland by examining the Northern Finland Intellectual Disability cohort. The results suggest that rare, damaging variation typically labeled monogenic is more likely to underlie more severe or syndromic intellectual disability, but is notably present in mild intellectual disability and non-syndromic intellectual disability as well.
The thesis was supervised by Professor Aarno Palotie and Professor Mark Daly.
In this thesis work, M Eng Pyry Helkkula focused on identifying opportunities for clinical translation for disorders with cardiometabolic risk factors with the help of protein-coding variation and endophenotypes of cardiometabolic diseases. The results highlight the utility of isolated and bottlenecked populations when searching for links between gene function and traits.
In the studies included in the dissertation, the aim was to boost the likelihood of finding links between gene function and cardiometabolic phenotypes by analyzing both endophenotypes of cardiometabolic disease endpoints and protein-coding variation.
The thesis was supervised by Professor Samuli Ripatti and Dr. Ida Surakka.
In this thesis work, LL Tuomo Kiiskinen designed and employed new genome-wide multi-phenotype approaches leveraging and combining biobank-scale genetic data with registry-based data points on lifelong health events in ways that were largely underutilised prior to this work. The three substudies focus on alcohol consumption, medication use and overall health burden measured as lost healthy life years.
The thesis was supervised by Professor Samuli Ripatti and Dr. Aki S. Havulinna.
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.
Computational tools for high-throughput drug combination screening, synergy scoring and predictive modelling in cancer
22 October, 2020
The main aim of Liye He's thesis was to develop computational models and tool for accelerating the process of identifying personalised drug combination therapy for cancer patients in a systematic manner, covering all the phases of the discovery process from experiment design to predicting and validating synergistic drug combinations.
The thesis work was supervised by Professor Tero Aittokallio and Assistant Professor Jing Tang.
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.
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.
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.
Genomic, metabolic and clinical profiling of dyslipidemias in families
November 6th, 2019
Cardiovascular diseases account for 30-40% of deaths in Western countries. Obesity and dyslipidemias, mainly elevated cholesterol and triglycerides, are well-established risk factors for cardiovascular diseases. However, these factors explain only a relatively small fraction of the individual disease risk. The main aim of Licentiate of Medicine Joel Rämö’s thesis was to identify risk factors for cardiovascular diseases beyond these traditional measures. The impact of family history and presence of fatty liver were of special interest to this work.
The thesis was supervised by Professors Aarno Palotie, Samuli Ripatti and Kirsi Pietiläinen.
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Transcriptomic data integration for precision medicine in leukemia
October 11th, 2019
MRes Ashwini Kumar’s thesis focused on utilizing gene expression information for advanced precision medicine outcomes in patients with hematological cancers. He started his thesis work in Caroline Heckman’s group at FIMM in 2012. FIMM Technology Centre’s RNA sequencing expert Pirkko Mattila acted as Ashwini’s co-supervisor.
In his thesis, Ashwini has utilized different bioinformatics and machine learning approaches for analysis of genomic and transcriptomic data with the aim to identify drug sensitivity and resistance biomarkers in leukemia patients.
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Moving beyond GWAS: Exploring the Function of the Gene LIN28B Associated with Pubertal Timing
10th October, 2019
The thesis work of M.Sc. Jaakko Leinonen focused on exploring the molecular mechanisms by which genetic variants nearby a gene called lin-28 homolog B (LIN28B) associate with pubertal timing. He did his thesis work under the supervision of Dr. Elisabeth Widén.
In his thesis, he utilized Finnish population cohorts and showed that LIN28B associates with variation in several body size parameters in adult humans. Furthermore, zebrafish experiments showed that modulating the amount of ling28b expression during embryogenesis affects the growth patterns of the fish. His results showed that the effects that LIN28B has on body size seem to be evolutionarily conserved. Read more about Jaakko's thesis project here.
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Studies on Drug Resistance and Molecular Biomarkers in Acute Myeloid Leukemia
October 4th, 2019
The thesis work of M.Sc. Riikka Karjalainen focused on investigating the biology of this devastating disease. The main objectives of her thesis were to identify novel mechanisms leading to drug resistance and biomarkers that could be used to predict its development. The thesis was supervised by Dr. Caroline Heckman and Professor Jonathan Knowles.
In her thesis, she tested the efficacy of more than 300 drugs against AML cells in stromal cell-conditioned medium and compared the data to results achieved using standard cell culture medium. The results demonstrated that the stroma-derived growth factors altered the response of many tested drugs. Furthermore she combined different types of data sources with the aim of identifying novel biomarkers for AML or venetoclax resistance. By applying machine learning methods for drug sensitivity and resistance testing and gene expression data, high expression of two calcium binding family genes were found as promising new biomarkers for venetoclax resistance. During her thesis project, Riikka has used a large number of different techniques and performed complex laboratory experiments. Read more about Riikka's thesis project here.
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Spatial Characterisation of Prostate Cancer by Multiplex Immunohistochemistry and Quantitative Image Analysis
27th September, 2019
The thesis work of M.Sc. Sami Blom focused on developing new methods that could be used to provide better understanding of the complex biological mechanisms behind prostate cancer development. The thesis was supervised by Dr. Teijo Pellinen and Prof. Olli Kallioniemi.
In his thesis, Sami focused on developing a novel multiplex Immunohistochemistry platform for quantitative analysis of formalin-fixed paraffin-embedded tissue samples. The aim was to develop an open-source method that is both highly robust and flexible enough to be widely adapted and utilized by researchers all over the world. Read more about Sami's thesis project here.
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The NUP98-NSD1 Fusion Gene in Acute Myeloid Leukemia
May 31st, 2019
M.Sc. Jarno Kivioja's thesis focused on a specific genetic subtype of AML with chromosomal rearrangement involving chromosomes 5 and 11. The thesis was supervised by Dr. Caroline Heckman and Prof. Kimmo Porkka.
The main objective of Jarno’s thesis was to facilitate molecular detection and treatment of AML patients with a rearrangement of the mentioned chromosomes. He identified a novel transcript variant that can be used for detecting the fusion gene more accurately from newly diagnosed patients and after the patients have been treated. In addition, Jarno combined data from high-throughput drug sensitivity and resistance testing with RNA sequencing with the aim of identifying novel effective compounds for AML patients having the NUP98-NSD1 fusion gene and concurrent FLT3-ITD mutation. Read more about Jarno's project here.
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Genetics of primaryimmunodeficiency in Finland
24th January, 2019
The thesis work of M.Sc. Luca Trotta focused on characterizin the molecular genetic basis of primary immunodeficiency in Finnish patients. His thesis was supervised by FIMM Research Director Janna Saarela and Docent Mikko Seppänen from the HUS Rare Disease Center.
In his thesis, Luca wanted to further depict the genetics of PIDs, targeting the possible disease-causing variants in Finnish patients with a suspicion of immune and/or haematological disorder but lacking a clinical diagnosis. The findings allowed the research group to expand the phenotypic spectrum of the studied diseases and to offer accurate genetic counselling for the families. Read more about Luca's thesis project here.
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FINEMAP: a Statistical Method for Identifying Causal Genetic Variants
18th January, 2019
M.Sc. Christian Benner’s doctoral dissertation presents the development of the FINEMAP software for fine-mapping causal variants in the associated genomic regions. The thesis work was supervised by FIMM group leaders Matti Pirinen and Samuli Ripatti.
During the past years, genome-wide association studies have been extremely successful in identifying genomic regions underlying various human diseases and quantitative phenotypes. However, any one associated genomic region can harbour hundreds or even thousands of correlated genetic variants. In his thesis, Christian focused on developing more efficient statistical tools to gain better understanding of the underlying biological mechanisms that lead to these associations. Read more about Christian's project here.
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Unravelling Lung Cancer Heterogeneity and Associated Therapeutic Responses Using In Vivo and Ex Vivo Model Systems
December 7th, 2018
The thesis work of M.Sc. Ashwini Nagaraj focused on investigating the role of tumor cell of origin in establishing lung cancer phenotypic and functional heterogeneity using genetically engineered lung cancer mouse models. The thesis was supervised by Dr. Emmy Vershuren and Dr. Denis Kainov.
Ashwini's thesis demonstrate that the tumor cell of origin is crucial in determining survival, lung cancer subtype, and associated immune microenvironment in the mouse model used. In addition, it ighlights that beyond understanding lung cancer at the genetic level, investigation of histotype-specific etiology, and spatially distributed functions including oncogenic signaling activities is important for designing effective therapies.
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Seven shades of tamoxifen resistance - Molecular mechanisms of drug resistance in breast cancer
October 23rd, 2018
M.Sc. Susanne Hultsch's thesis work focuses on the cellular events that precede the development of resistance to one the most important breast cancer treatments, tamoxifen. The thesis was supervised by Sara Kangaspeska, Olli Kallioniemi and Vilja Pietiäinen.
The overall goal of Susanne’s thesis was to create and utilize breast cancer cell line models to explore the resistance mechanisms of breast cancer and find potential prognostic markers as well as drug vulnerabilities. Susanne says that even after "70 years of research, drug resistance is still a problem and we need to learn more about mechanisms of it and vulnerabilities associated with these mechanisms to be able to treat drug-resistant cancers".
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Improving Precision in Therapies for Hematological Malignancies
October 12th, 2018
M.Sc. Muntasir Mamun Majumder's thesis focused on accelerating the adoption of precision medicine practices in myeloma and other hematological cancers. The thesis was supervised by Caroline Heckman and Krister Wennerberg.
The main goal of Mamun's thesis was to identify individualised treatment decisions and to facilitate drug discovery efforts for multiple myeloma. The research covered all the key aspects of precision medicine from method development, patient stratification and biomarker identification to validating the clinical utility of the findings.
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Machine Learning for Systems Pharmacology
October 5th, 2018
M.Sc. Anna Cichonska's thesis work was supervised by Tero Aittokallio and Matti Pirinen (FIMM) and Professor Juho Rousu (Aalto University). Anna received an "Aalto Univeristy dissertation award 2019" on her thesis.
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Targeting Key Survival Signaling Pathways for The Treatment of Leukemia
September 28th, 2018
M.Sc. Heikki Kuusanmäki's thesis approached the challenges of transforming the new knowledge on leukemia genetics into clinically actionable strategies by combining genetic profiling with high-throughput drug sensitivity testing in patient derived leukemia cells. The thesis work was supervised by Caroline Heckman and Satu Mustjoki.
The main objective of Heikki's thesis was to identify novel driver mutations in two rare leukemia types, large granular lymphocyte (LGL) leukemia and T-cell acute lymphoblastic leukemia (T-ALL). Furthermore, he wanted to develop a new flow cytometry-based drug screening assay to assess cell population specific drug responses in heterogenous leukemia samples.
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Clonal evolution and heterogeneity of cancer in the context of individualized medicine
August 24th, 2018
M.Sc. Poojitha Ojamies' thesis work focused on developing sequencing and bioinformatics methods to study spatial and temporal tumor heterogeneity and evolution of cancer subclones. The thesis was supervised by Prof. Olli Kallioniemi and Dr. Maija Wolff.
The goal of Poojitha’s thesis was to comprehensively investigate cancer evolution and heterogeneity as well as understand drug responses at a subclone level in the context of individualised cancer treatment. Her thesis project is part of FIMM’s “Individualised systems medicine in cancer” Grand Challenge programme.
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Computer vision for tissue characterization and outcome prediction in cancer
August 24th, 2018
M.Sc. (Tech) Riku Turkki's thesis focused on investigating the use of computer vision for tissue characterisation and patient outcome prediction in cancer. The thesis work was supervised by Johan Lundin and Nina Linder.
Although a lot of progress is made in cancer diagnostics and outcome prediction, histological analysis of tumour tissue still has a key role. Manual histological evaluation is time-consuming and prone to subjective assessment. In his thesis, Riku tackled this challenge by developing computer vision aided processes and testing their applicability for clinical purposes. The main aim of his dissertation was to investigate the use of computer vision for tissue characterisation and patient outcome prediction in cancer.
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Functional testing of urological cancer models by RNAi and drug libraries
August 13th, 2018
M.Sc. Khalid Saeed’s thesis work focused on identifying novel future treatment strategies for prostate, renal and kidney cancer. His thesis was supervised by Olli Kallioniemi, Päivi Östling and Taija af Hällström.
In his thsesis, Khalid’s was aimed to generate molecular profile and drug testing data using patient-derived cancer cells. His proof-of-concept studies show that this kind of data can be used to help clinicians in treatment decision and to facilitate the early selection of the best drug candidates for clinical development.
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Molecular Effects of Obesity and Related Metabolic Risk Factors – A Transcriptomics and Metabolomics Approach
June 8th, 2018
M.Sc., MBA Maheswary Muniandy’s thesis focused on studying obesity using omics data and bioinformatics tools. The thesis work was supervised by Dr. Miina Ollikainen and Prof. Kirsi Pietiläinen.
The global obesity epidemic is worsening in most parts of the world and the implications of obesity regarding both personal health and health-economics are enormous. Understanding the molecular mechanisms leading to and caused by obesity could help in designing personalised treatment to support weight-loss. In her thesis Maheswary tried to gain understanding of the complex, multifactorial biology behind obesity using bioinformatics tools.
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Integrative bioinformatics of functional and genomic profiles for cancer systems medicine
June 8th, 2018
M.Sc. Alok Jaiswal’s thesis focused on developing novel computational models and approaches for data analysis to facilitate extracting reproducible and meaningful information from the genomic and functional cancer datasets. The thesis work was supervised by Tero Aittokallio and Jing Tang.
The goal of Alok's thesis was to provide information about the genes driving cancer that could be utilised in identifying promising cancer drug candidates and predictive biomarkers. He developed an approach to remove noise from genome-wide RNAi screens and also integrated genomic profiles with the RNAi screen data to be able to predict major cancer driver genes and their synthetic lethal partners.
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Analysis of somatic mutations in leukemias
May 21st, 2018
M.Sc. Samuli Eldfors' thesis focused on identifying clinically important somatic mutations contributing to the development and treatment response of different leukemias. The thesis work was supervised by Dr. Caroline Heckman and Prof. Olli Kallioniemi.
In his thesis, Samuli has identified somatic mutations in three leukemia types and analyzed the biological and clinical significance of these mutations. A major part of the work has been the development of a computational workflow and the application of bioinformatics approaches to detect mutations based on whole exome sequencing data.
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In Search of Improved Outcome Prediction of Prostate Cancer – A Biological and Clinical Approach
May 11th, 2018
The thesis of M.Sc. Andrew Erickson focused on identifying novel biological and clinical factors that could be utilized in the outcome prediction of prostate cancer. The thesis was supervised by Tuomas Mirtti and Antti Rannikko.
In the first part his thesis work, Andrew focused on outcomes of low-risk active surveillance patients. And in the second part of the thesis, the focus was on the long-term outcome of primarily treated patients.
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Association and interplay of genetic and epigenetic variants in smoking behavior
April 20th, 2018
The thesis of M.Sc. Richa Gupta focused on studying the links between the smoking behaviour and genetic as well as epigenetic variation. The thesis work was supervised by Jaakko Kaprio and Miina Ollikainen.
Smoking is the single greatest preventable cause of death in the world today. In her thesis, Richa utilised several different omics data, including genetics (assessed by single nucleotide polymorphisms), epigenetics (assessed by DNA methylation), as well as transcriptomics data to identify novel associations and validating the involvement of known candidate genes in smoking behaviour.
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Bioinformatic identification of disease driver networks using functional profiling data
March 23rd, 2018
The thesis of M.Sc. Agnieszka Szwajda was supervised my FIMM-EMBL Group Leaders Tero Aittokallio and Krister Wennerberg.
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Chemical systems biology studies of triple negative breast cancer cell lines
December 14th, 2017
The thesis of M.Sc Prson Gautam focused on exploring drug vulnerabilities of triple negative breast cancer (TNBC) cell lines to learn more about the molecular pathology of TNCB and to identify novel, druggable target molecules. The thesis work has been supervised by Tero Aittokallio and Krister Wennerberg.
In his thesis, Prson set up better ways of using the existing cell viability and toxicity readouts to determine drug responses using TNBC cell lines as a model. Furthermore, he developed novel drug response metrics and scores.
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Consequences of balanced translocations and loss-of-function mutations
November 3rd, 2017
The thesis work of M.Sc. Tiia Maria Luukkonen aimed to characterize the molecular and phenotypic consequences of several balanced chromosomal rearrangements utilizing next generation sequencing. The thesis was supervised by Professor Aarno Palotie (FIMM) and Docent Teppo Varilo (UH).
In her thesis, Tiia studied the impact of a set of loss-of-function mutations on atopic dermatitis. She studied the consequences of balanced translocations in four Finnish families with different but severe symptoms. The thesis work made substantial progress in understanding the genetic causes of the symptoms the studied individuals had.
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Nicotine Dependence – Identifying the Contribution of Specific Genes
June 2nd, 2017
M.Sc. Jenni Hällfors’ thesis focused on identifying genes predisposing individuals to smoking behavior and nicotine dependence. The thesis work has been supervised by Anu Loukola and Jaakko Kaprio.
In her thesis, Jenni concentrated on the best characterized smoking behavior locus on chromosome 15, which harbors three nicotine receptor subunit genes. She was able to confirm the earlier association findings and show that variation within this locus explains approximately 1% of the inter-individual differences in the daily smoking quantity.
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Quantitative modeling and analysis of drug screening data for personalized cancer medicine
March 24th, 2017
The thesis work of M.Sc. Bhagwan Yadav focused on developing novel computational models for quantification of drug responses and to implement them on cancer patient data. The thesis has been supervised by FIMM-EMBL group leader Dr. Tero Aittokallio.
In his thesis Bhagwan describes three novel models for the analysis and integration of drug sensitivity data and demonstrates their robustness and better performance compared to the existing ones.The most important computational pipeline developed in the thesis is based on a novel metric to quantify drug response, called the drug sensitivity score (DSS).
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Novel Genetic Determinants of Breast Cancer Progression
December 5th, 2016
The thesis work of M.Sc. Daria Bulanova focused on identifying new breast-cancer predisposing mutations and to elucidate the biological mechanisms underlying these genetic findings. The thesis was supervised by FIMM-EMBL Group Leader Sergey Kuznetsov.
In her thesis, Daria and her collaborators identified a promising mutation in an orphan G protein-coupled receptor-encoding gene GPRC5A using modern exome sequencing technologies. She also explored the effect of GPRC5A deficiency on cancer progression.
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Discovery of Small Molecule Modulators of Ras Superfamily Proteins – Studies of MgcRacGAP and Ras
September 9th, 2016
The thesis work of M.Sc. Arjan van Adrichem aimed at identifying new small molecule modulators specifically targeting GTPase regulatory proteins through different high-throughput screening approaches. The thesis was supervised by FIMM-EMBL Group Leader Krister Wennerberg and Dr. Outi Monni.
In his thesis, Arjan focused on proteins that regulate guanine triphosphatases (GTPase), such as GTPase activating proteins (GAPs). When GTPase regulatory proteins instead of the GTPases themselves are targeted, a much more specific inhibition of selected cellular signaling pathways can be expected. Arjan's thesis led into identification of a molecule called MINC1 as a specific inhibitor of a certain GTPase-activator, MgcRacGAP. He was the first in the world to successfully target such a protein and thus to prove that they are both screenable and druggable.
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Identification of new genetic syndromes with epilepsy by whole-exome sequencing
June 22th, 2016
The thesis work of M.Sc. Mikko Muona aimed at characterizing the molecular genetic basis of severe epilepsy syndromes utilizing whole-exome sequencing. The thesis was supervised by Professor Aarno Palotie and Professor Anna-Elina Lehesjoki.
For the thesis, Mikko studied patients with progressive myoclonic epilepsy and with severe infantile epilepsy. The rare nature of the deceases made international collaboration and data sharing crucial. The progressive myoclonus epilepsy patients that Mikko studied were mainly of European and Asian origin, and collected through long-lasting international collaboration.
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Functional discovery of microRNAs and their targets in prostate and breast cancer: impact on hormonal regulation and cell proliferation
June 21th, 2016
The thesis work of Anna Aakula focused on creating a wide picture of miRNAs that regulate genes important for prostate cancer proliferation. MiRNAs have been found to be important and well conserved regulators of gene expression. The thesis was supervised by Olli Kallioniemi and Päivi Östling.
During the thesis project Anna studied the effect of more than 1100 miRNA molecules using high-throughput phenotypic screens and was able to find 13 miRNA that regulated androgen receptor expression, mainly by targeting an extended 3’ untranslated region of the gene. She also recognized a set of miRNAs that regulate several aberrantly expressed genes important for the prognosis of prostate cancer.
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Bioinformatic tools for analysis, mining and modelling large-scale gene expression and drug testing datasets
11 March, 2016
The thesis work of M.Sc. John Patrick Mpindi focused on developing and testing of modern bioinformatics methods and analysis pipelines and apply them on biomedical data with relevance to cancer research. The thesis was supervised by Olli Kallioniemi.
During his thesis project, John Patrick developed bioinformatic tools for analyzing large-scale biomedical data sets. He concentrated on two types of biomedical data: microarray based gene expression datasets as well as drug sensitivity and resistance testing datasets and developed a novel algorithm for detecting outliers in gene expression datasets.
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Studying the functional relevance of lung cancer genetic drivers in their physiological niche
February 19th, 2016
The thesis work of M.Sc. Jenni Lahtela focused on finding clinically meaningful information on genetic and cell type-specific factors contributing to the development and progression of lung cancer. Lung cancer is the most common cause of cancer related deaths worldwide but often it is diagnosed only at an advanced state due to the asymptomatic disease progression. The thesis was supervised by FIMM-EMBL Group Leader Emmy Verschuren.
The basis of Jenni's thesis was to validate the functional importance of a EPHA3 gene of which mutations are commonly found in lung tumours and based on prior results the gene was suspected to act as a tumour suppressor. She also studied the impact of the cell-of-origin on lung cancer development by utilising genetically engineered mouse models of lung cancer.
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Individualized chemical systems medicine of acute and chronic myeloid leukemia
October 20th, 2015
Unlike most current efforts in cancer precision medicine focus on genomic profiling, the thesis work of M.Sc. Tea Pemovska concetrated on developing a method for drug sensitivity testing that could be used to functionally profile leukaemia patients’ cells in order to identify personalised therapy options. The thesis work was supervised by EMBL Group Leader Krister Wennerberg and Professor Kimmo Porkka.
Tea's research focused on patients with haematological cancers, such as acute and chronic myeloid leukaemia, for both clinical and practical reasons. She explains that there is a great need of novel treatment options since the standard therapy for the acute form hasn’t changed in decades and patients' predictions remain poor. In Tea's thesis project a high-throughput drug sensitivity and resistance testing method for leukaemia patient samples was developed and the results were further combined with deep molecular profiling and explored in a translational setting together with a team of haematologists.
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Rad51c is a tumor suppressor in mammary and sebaceous glands
September 8th, 2015
The thesis work M.Sc. Manuela Tumiati focused on understanding the mechanisms by which defects in another DNA repair gene, RAD51C, predispose women to breast and ovarian cancer. Many of the known breast cancer susceptibility genes, such as BRCA1, are involved in repair of DNA double-strand breaks. The thesis was supervised by FIMM-EMBL Group Leader Sergey Kuznetsov.
An important part of Manuela's thesis was to generate a conditional knock-out mouse model that would enable studying the Rad51c gene. She was i.e. able to show that loss of Rad51c alone is not sufficient to trigger tumorigenesis but inactivation of Trp53 gene is also needed. Additionally she detected a significant close resemblance between mouse and human mammary carcinomas.
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Implications of BRCA1 mutations in basal-like breast cancer development and treatment
June 16th, 2015
The thesis work of M.Sc. Yuexi Gu focused on finding a better understanding for the biological nature of BRCA1-mutant breast cancers in order to develop potential therapeutics for their treatment. Women having a mutation within BRCA1 gene have up to 80% chance of developing breast cancer in their lifetime. The thesis was supervised by FIMM-EMBL Group Leader Sergey Kuznetsov.
In his study, Yuexi and the research group collected and characterized four breast cancer cell lines bearing different BRCA1 mutations. The group also utilized siRNA-mediated gene silencing of the BRCA1 gene and were able to show that two proteasome inhibitors selectively killed the BRCA1-depleted cells.
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Influenza A virus-host interactions and their control by viral non-structural protein NS1
April 17th, 2015
The thesis work M.Sc. Maria Anastasina focused on studying the role of the non-structural protein NS1 of influenza A virus. This protein is a key regulator of influenza A viral interactions with the host cell. The thesis was supervised by FIMM-EMBL Group Leader Denis Kainov and Professor Sarah Butcher.
In her thesis, Maria describes several new functions of NS1 in regulation of virus host interactions. She says: "Although the influenza A NS1 protein has been extensively studied over the past few decades the understanding is still far from complete"
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The Genetics of Pubertal Growth and Timing
April 17th, 2015
The main aim of M.Sc. Diana Cousminer’s thesis work was to identify genetic variants influencing pubertal growth and development in both sexes. Pubertal development has major health implications since variation in pubertal growth and timing correlates with altered risk for many diseases in adulthood. The thesis was supervised by Elisabeth Widén.
During her research, Diana studied both Finnish families with an extreme delay in normal pubertal timing, Finnish population-based samples and large cohorts of European origin comprising nearly twenty-thousand individuals. She was able to show e.g. that a genetic region that was earlier identified to be a menarche locus, contains variants that regulate postnatal growth and have a strong influence on growth during puberty as well as pubertal timing in both sexes.
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Rare Genomic Deletions Underlying Schizophrenia and Related Neurodevelopmental Disorders
December 19th, 2014
The thesis work of M.Sc. Olli Pietiläinen focused on studying the role of large chromosomal copy number variants in schizophrenia. It is a highly heritable and relatively common mental disorder with 1-2% of the population having a schizophrenia diagnoses. The thesis was supervised by professor Aarno Palotie, professor Jaana Suvisaari and the late Academician of Science Leena Palotie.
In his study, Olli showed that a small proportion of the genetic risk of schizophrenia is due to rare, large chromosomal deletions. The phenotypic spectrum of the symptoms associated with these deletions was shown to vary from mental disorders to learning difficulties. The genetic findings together suggest that schizophrenia is as biological as any other somatic disorder and that it can be regarded to be one form of neurodevelopmental disorder.
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Genetics of Circulating Blood Lipids
November 7th, 2014
M.Sc. Ida Surakka’s thesis work focused on identifying genetic markers and biological pathways behind circulating blood lipid levels. Circulating blood lipids such as cholesterol and triglycerides are well-established risk factors for cardiovascular diseases. The thesis was supervised by Professor Samuli Ripatti.
In her thesis Ida studied several large cohorts of European origin comprising tens of thousands of individuals. Nearly a hundred genetic loci associated with lipid levels were identified using large-scale genome-wide approaches.
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Influenza virus-host interactions and their modulation by small molecules
May 9th, 2014
The main aim of M.Sc. Oxana Denisova's thesis work was to find next-generation antiviral agents to combat influenza virus infection. The thesis was supervised by Dr. Denis Kainov.
In her thesis Oxana investigated influenza virus-host cell interaction in detail. She built and screened a library of small molecule inhibitors targeting host factors and potentially interfering with influenza virus infection. The research showed that certain host functions are actively exploited by influenza virus during infection and that these functions could be temporally inhibited with small molecules to block influenza infection in cell culture.
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November 8th, 2013
The thesis work of of M.D. Tiina Lehtimäki concentrated on the long-term prognosis of breast cancers. She compared screen-detected breast cancers to cancers found by other methods. The thesis was supervised by Dr. Johan Lundin and Academy Professor Heikki Joensuu.
Tiinas thesis was based on a FinProg patient cohort which consists of nearly 3,000 breast cancer patients diagnosed in Finland in early 90's. Tiina had a major role in designing, organizing and collecting this valuable database that contains both clinical and long-term survival information as well as pathological tumor samples. She visited all University Hospitals in Finland and collected each patient’s histological tumor samples whenever available.
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Genetic risk profiles for coronary heart disease
November 8th, 2013
The thesis work of M.Sc. Emmi Tikkanen focused on evaluating the incremental value of genetic information in coronary heart disease (CHD) risk assessment. The thesis has been supervised by Professor Samuli Ripatti.
In her thesis Emmi utilized the results from large-scale genome-wide association studies that have identified over 40 genetic regions associated with CHD risk. She constructed genetic risk scores and evaluated the genetic risk for CHD and its risk factors in over 50,000 Finnish and Swedish individuals. Emmi feels that the most important result of here study is finding that utilizing genetic information in CHD risk assessment improves the prediction over traditional risk factors and family history.
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