FIMM Dissertations 2019

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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Joel Rämö’s thesis re­thinks the causes of dys­lip­idemias in fam­il­ies

Joel Rämö's e-thesis

JR
Joel
Rämö
Postdoctoral researcher
Institute for Molecular Medicine Finland
Field of science Biomedicine

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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Ash­wini Ku­mar’s dis­ser­ta­tion shows the power of bioin­form­at­ics in pre­ci­sion medicine

Ashwini Kumar's e-thesis

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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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Jaakko Leinon­en’s doc­toral thesis de­mon­strates the value of fol­low-up stud­ies of ge­netic as­so­ci­ations

Jaakko Leinonen's e-thesis

 

JL
Jaakko
Leinonen
Postdoctoral researcher
Institute for Molecular Medicine Finland
Field of science Genetics, developmental biology, physiology

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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Riikka Kar­jalain­en’s dis­ser­ta­tion provides new clues on drug res­ist­ance in acute my­el­oid leuk­emia

Riikka Karjalainen's e-thesis

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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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Sami Blom’s dis­ser­ta­tion provides novel tools for analysis of tu­mor tis­sue in pro­state cancer

Sami Blom's e-thesis

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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Jarno Ki­vi­oja’s dis­ser­ta­tion ad­vances mo­lecu­lar de­tec­tion and treat­ment of acute my­el­oid leuk­emia

Jarno Kivioja's e-thesis

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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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Luca Trot­ta’s doc­toral thesis de­mon­strates the power of whole-ex­ome se­quen­cing as the dia­gnostic tool for primary im­mun­ode­fi­cien­cies

Luca Trotta's e-thesis

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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Chris­tian Ben­ner’s dis­ser­ta­tion de­mon­strates cut­ting-edge in­nov­a­tions in stat­ist­ical fine-map­ping meth­od­o­logy

Christian Benner's e-thesis