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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Daria Bulanova’s doctoral thesis pinpoints GPRC5A as a novel breast cancer gene.

Daria Bulanova's e-thesis.

Field of science Biomedicine

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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Ar­jan van Ad­ri­chem’s doc­toral thesis de­mon­strates that there is no such thing as an im­pos­sible drug tar­get.

Arjan van Adrichem's e-thesis.

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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Mikko Muon­a’s doc­toral thesis de­mon­strates the power of whole-ex­ome se­quen­cing in the gene dis­cov­ery of rare dis­eases.

Mikko Muona's e-thesis.

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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Anna Aakula’s dissertation shows the relevance of miRNAs to prostate cancer proliferation.

Anna Aakula's e-thesis.

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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John Patrick Mpindi’s dissertation demonstrates the importance of standardized bioinformatic methods in individualized cancer medicine.

John Patrick Mpindi's e-thesis.

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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Jenni Lahtela’s dis­ser­ta­tion shows the im­port­ance of the physiolo­gical niche in lung cancer de­vel­op­ment and pro­gres­sion.

Jenni Lahtela's e-thesis.

Senior Researcher
Institute for Molecular Medicine Finland
Field of science Biochemistry, cell and molecular biology

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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Tea Pemovska’s doctoral thesis demonstrates how cancer care becomes truly personalised.

Tea Pemovska's e-thesis.

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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Manuela Tumiati’s dissertation generated a novel breast cancer mouse model with potential to explore therapeutic approaches.

Manuela Tumiati's e-thesis.

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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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Yuexi Gu’s dissertation unveils new features of the breast cancer type 1 susceptibility protein.

Yuexi Gu's e-thesis.

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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Maria Anastasina’s dissertation reminds us never to underestimate the capabilities of viruses to control their host cells.

Maria Anastasina's e-thesis.

University Researcher
Molecular and Integrative Biosciences Research Programme
Field of science Biomedicine, Biochemistry, cell and molecular biology

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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Timing really is everything, shows Diana Cousminer’s dissertation.

Diana Cousminer's e-thesis.

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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Broken genome can be the cause of a broken mind, shows Olli Pietiläinen.

Olli Pietiläinen's e-thesis.

Senior Researcher
Neuroscience Center

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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Ida Surakka’s dissertation shows the power of large cohort studies in identifying genetic determinants of lipid levels.

Ida Surakka's e-thesis.

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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Oxana Denisova’s dissertation shows the potential of small molecule inhibitors as next-generation anti-influenza drugs.

Oxana Denisova's e-thesis.

Screen-detected breast cancer and prognosis

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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The dissertation of Tiina Lehtimäki demonstrates the importance of detection method in the long-term prognosis of breast cancers.

Tiina Lehtimäki's e-thesis.

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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Emmi Tikkanen aims high with genetic predictions of coronary heart disease.

Emmi Tikkanen's e-thesis.