| Maare |
|
Arffman |
|
Arffman Maare |
The role of liquid biopsy in revealing clinical and biological heterogeneity in aggressive B-cell lymphomas |
Large B-cell lymphomas (LBCL) are clinically and biologically heterogenous group of aggressive lymphoid cancers. Although treated with a curative intent, around 30% of the patients do not respond to therapy and have extremely poor survival. As treatment failure is difficult to predict with current clinical risk scores and PET-CT imaging, better clinically applicable tools are needed.
Our aim is to develop accurate, minimally invasive methods to guide the diagnosis and risk-stratification of LBCL patients. We hypothesize that liquid biopsy outperforms current clinical methods in predicting treatment response. To prove this, we will: 1) explore host response to the disease by analyzing serum protein profiles, tumor microenvironment, and circulating tumor DNA (ctDNA) in patients from the Nordic LBC-05 trial; 2) improve ctDNA-based risk profiling by integrating mutation and copy number aberration (CNA) landscapes using serial blood samples and clinical data from the LBC-06 trial; and 3) expand the ctDNA repertoire by investigating clinically relevant epigenetic modifications, such as methylation patterns and fragmentomic profiles from subsets of LBC-05 and LBC-06 patients.
We believe our findings will translate into clinical benefit of lymphoma patients. |
|
Cancer and Cell Based Cancer Research |
4,000 € |
| Jefim |
|
Brodkin |
|
Brodkin Jefim |
Molecular subtypes and novel serum biomarkers if gastric cancer |
Gastric cancer is the fifth most common cancer worldwide and remains the fifth leading cause of cancer-related death. Despite the rapid decrease in incidence in the Western countries, gastric cancer continues to have a very poor prognosis. This is mainly due to late diagnosis and a lack of effective treatments for advanced disease.
We examined 283 gastric cancer patients who underwent surgery at Helsinki University Hospital between 2000 and 2009, along with 48 healthy controls. To immunohistochemically determine the molecular subtypes, we constructed a tumor tissue microarray (TMA). Also, we measured serum protein concentrations of 48 different cytokines and growth factors using Bio-Rad’s Multiplex Assay kits to find novel serum biomarkers.
Immunohistochemical analysis can identify prognostically different molecular subtypes of gastric cancer. The method is inexpensive and fast, yet reveals significant information for clinical decision-making. We found multiple previously unreported diagnostic and prognostic serum biomarkers. This provides new support to further explore the effect of these inflammatory molecules in gastric cancer and offer new insights into the immunological microenvironment of the disease. This may help in finding novel non-invasive diagnostic methods as well as potential new targets for treatments. |
|
No specific grant area |
4,000 € |
| Jenna |
|
Broman |
|
Broman Jenna |
Ischemic stroke in the young: Long-term outcomes and the impact of psychiatric medication use |
Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Approximately 10% of ISs affect individuals under 50, and their incidence is increasing. In this age group, the consequences of IS can be particularly severe, making it essential to understand the long-term outcomes in young patients. Moreover, neuropsychiatric symptoms and complications affect around one-third of stroke survivors and may negatively impact recovery. This thesis aimed to investigate the long-term outcomes of IS and assess the prevalence and long-term consequences of psychiatric medication use in young patients.
The first two studies focused on the initiation of post-stroke antidepressants (PSAD) within the first year after IS and their association with long-term cardiovascular events and all-cause mortality. Patients were identified from the retrospective Helsinki Young Stroke Registry (HYSR), which includes 1008 consecutive patients aged 15–49 with first-ever IS treated at Helsinki University Hospital between 1994 and 2007. The third study examined the 10-year risk of recurrent vascular events and mortality in young patients after IS or transient ischemic attack (TIA) in a European multicenter cohort. The fourth study characterized HYSR patients who used antipsychotics either prior to or de novo after IS and evaluated their association with long-term recurrent vascular events and all-cause mortality. |
|
Neurological and Cerebrovascular Disorder |
4,000 € |
| Vaishali |
|
Chaurasiya |
|
Chaurasiya Vaishali |
Adipose Tissue Vascular Distortion in Obesity: Mechanisms and Rescue by Incretin Agonists |
Obesity leads to profound distortions in adipose tissue (AT) vasculature, disrupting the critical crosstalk between endothelial cells (ECs) and adipocytes. This impaired communication results in reduced insulin sensitivity, chronic inflammation, and progression of metabolic diseases such as type 2 diabetes and cardiovascular diseases. Despite its significance, the molecular mechanisms underlying EC-adipocyte dysfunction in obesity remain poorly understood, limiting therapeutic innovation. This project aims to elucidate these mechanisms by isolating ECs and adipocyte progenitor cells from visceral AT of obese and lean individuals, establishing a novel co-culture system (MAAECC), and applying multi-omics analyses (proteomics, lipidomics, metabolomics) to identify key molecular signatures of unhealthy obesity. Furthermore, we will investigate the therapeutic potential of next-generation incretin agonists (GLP-1, GIP, GCGR dual/triple agonists) in restoring healthy EC-adipocyte interactions and metabolic function. Drug target identification (CETSA) and transcriptomic profiling will clarify mechanisms of action. Our findings will provide new insights into adipose tissue vascular dysfunction and support the development of innovative incretin-based therapies for obesity and related metabolic diseases like cardiovascular diseases, fatty liver etc. |
|
Cardiovascular |
6,000 € |
| Yingjia |
|
Chen |
|
Chen Yingjia |
Ex vivo drug response profiling for outcome prediction in acute myeloid leukemia (AML) - a prospective observational study |
In this study, we will develop a robust and interpretable prognostic approach that makes use of ex vivo drug response profiling in patient-derived cells and computational methodologies, such as machine learning (ML), with the aim to predict the overall survival of patients with acute myeloid leukemia (AML) after standard therapies, and to provide valuable insights about treatment response and disease progression. By integrating cohorts of AML patients collected in multiple studies, we will evaluate the prognostic power of the drug response data and ML models, compared to transcriptomics and other omics data from the same patients. The systematic prognostic approach can identify drug biomarkers associated with the clinical response and guide selection of treatment options for AML patients. Once carefully tested in the present project, we expect that approach will have potential for wider clinical impact in cancer treatment beyond AML. |
|
Cancer and Cell Based Cancer Research |
4,000 € |
| Gabin |
|
Drouard |
|
Drouard Gabin |
Mapping Environmental Contributors to Omic Variation in Monozygotic Twin Pairs |
Omics technologies — which enable the comprehensive quantification of biological molecules — have transformed medical research by offering insights into mechanisms underlying disease. While variation in omics profiles is often assumed to be largely genetically determined, twin studies provide a unique framework to disentangle genetic and environmental contributions. My PhD research aims to evaluate how both genetic and environmental factors shape omics variation and contribute to disease risk, by using twins and related study designs. In my final PhD project, I will investigate intra-pair differences in protein and metabolite levels among 131 monozygotic twin pairs aged 21–24 years from the FinnTwin12 cohort. Because monozygotic twins share identical genomes, any molecular differences between them can be attributed to environmental influences. These differences will be analyzed in relation to nearly 100 environmental exposures, including neighborhood-level indicators (e.g., green space, population age structure) and familial or social factors. Clustering methods will be applied to identify patterns of non-genetic co-variation between omics features and environmental variables. Finally, associations with disease outcomes will be examined to identify potential pathways linking environmental exposures to disease through molecular phenotypes. This study may inform more precise personalized medicine strategies and guide the development of more effective public health policies. |
|
No specific grant area |
4,000 € |
| Sofia |
|
Forstén |
|
Forstén Sofia |
Understanding the effects of immune checkpoint inhibitors in treatment of AML patients with single-cell transcriptomics |
While immune checkpoint inhibitors (ICIs) show limited efficacy in acute myeloid leukemia (AML), some patients achieve lasting responses, highlighting the need to understand the immunomodulatory effects and immune phenotypes of different ICIs to develop new AML treatments.
We analyzed single-cell RNA and T cell receptor sequencing data from 37 AML patients in clinical trials with ICIs (anti-CTLA4, anti-PD1, or anti-TIM3), pooling 122 bone marrow samples to create a dataset of nearly 600,000 cells.
Our findings show PD1 and CTLA4 expression mainly in T cells and TIM3 expression in NK and myeloid cells, indicating distinct treatment effects as well. Responders had more mature NK cells pre-treatment and showed more transcriptional changes, especially with anti-TIM3 and anti-PD1, which upregulated NF-κB and interferon (IFN) pathways. High PD1 expression in CD8+ T cells led to more expanded clones and IFN pathway upregulation in anti-PD1 responders, contrasting with other treatments. However, T cell expansion did not consistently correlate with treatment outcomes, though T cell clones in anti-PD1 responders shifted towards a more cytotoxic phenotype, unlike the smaller, less cytotoxic clones in anti-TIM3 responders.
Our study reveals distinct immune activation mechanisms for each ICI, with no single immune cell population consistently predicting treatment response, underscoring the importance of personalized AML treatment strategies. |
|
No specific grant area |
4,000 € |
| Yu |
|
Fu |
|
Fu Yu |
The role of X chromosome in the genetics of complex traits and autoimmune diseases and sex differences within |
The X chromosome (chrX) has long been hypothesized to play a role in the etiology of sex-biased traits and diseases. However, it remains understudied in genetic association studies due to analytical and interpretational challenges posed by its unique biology—namely, hemizygosity in males and the need for dosage compensation to balance expression between sexes and between chrX and autosomes. In my first first-author publication, we conducted the largest genome-wide analysis of chrX to date, using data from > 340k individuals in the UK Biobank and > 410k in FinnGen, across 48 complex traits. We showed that chrX contributes to trait heritability in a manner shaped by dosage compensation. We observed near-full X chromosome inactivation (XCI), along with evidence of XCI escape influencing height, and partial dosage compensation between chrX and autosomes. We extended such analytical approach to autoimmune diseases that are often more common in women than in men. Through meta-analysis of UK Biobank and FinnGen across 13 disease endpoints (case numbers 1,718–81,718), we identified 7/14 novel chrX loci—several near genes known to escape XCI in immune cells. We are currently expanding our study to examine the effects of skewed XCI on autoimmune disease risk in females. Overall, our study highlight the non-negligible contribution of chrX to complex traits and diseases and provide insight into how chrX biology may contribute to the sex differences in complex traits and disease risks. |
|
No specific grant area |
4,000 € |
| Alex |
|
Halme |
|
Halme Alex |
Understanding and preventing thrombosis and bleeding in surgery and oncology |
The risk of thromboembolism can be reduced with thromboprophylaxis, but current evidence on when thromboprophylaxis should be used in surgical and oncological patients is weak. Since pharmacological thromboprophylaxis lowers the risk of thromboembolism but increases the risk of bleeding, understanding the timing of bleeding events and the risk of thrombosis is crucial for determining appropriate use.
This dissertation examines the timing of bleeding events in surgery using data from the prospective VISION study, which recruited over 40 000 patients undergoing noncardiac surgery in 14 countries. It also includes a massive systematic review and meta-analysis of procedure-specific complication risks in urologic surgery and kidney transplantation. Finally, the dissertation features a multinational survey on oncologists’ prescribing practices during neoadjuvant chemotherapy for muscle-invasive bladder cancer, alongside a second meta-analysis assessing thrombotic and bleeding risks in this setting. These research findings will inform future randomized trials and enable evidence-based thromboprophylaxis in surgery and oncology worldwide. |
|
Urological research |
4,000 € |
| Ronja |
|
Hotakainen |
|
Hotakainen Ronja |
NGS based rare disease diagnostics and carrier screening |
Next-generation sequencing has transformed genetic diagnostics, yet diagnosing rare diseases remains difficult due to incomplete gene–phenotype associations and complex variant interpretation. In Finland, the unique genetic landscape shaped by founder effects and bottlenecks makes international carrier screening guidelines poorly applicable.
Our goal is to develop a population-specific carrier screening strategy for Finland. Using gnomAD v4 data, we identified AR disease genes with a cumulative pathogenic variant frequency ≥1/200 in the Finnish population—revealing a 3% risk for Finnish couples to be rare disease carriers. We will refine risk estimates using virtual couples and exome data from ~3,000 HUSLAB patients of Finnish genetic background.
Currently, Finnish clinical labs screen only for known variants in patients with a relevant family history. In contrast, our study evaluates whether broader gene-based screening—including founder variants—would better identify at-risk couples. A retrospective review of 3,000+ HUSLAB screenings (2010–2020) will define the optimal strategy.
This research aims to reshape Finland’s approach to carrier screening—with potential global impact on screening policy in genetically isolated populations. |
|
No specific grant area |
4,000 € |
| SeoJeong |
|
Joo |
|
Joo SeoJeong |
Decoding the Roles of Circulating Extracellular Vesicles in Brain-dead Donors |
Lung transplantation is the final treatment option for end-stage pulmonary diseases, yet donor lung utilization remains limited due to donor-related injuries and strict selection criteria. Brain death in donors triggers detrimental biological cascades that may compromise organ quality. Extracellular vesicles (EVs), lipid bilayer-enclosed nanoparticles released by cells, are abundant in circulation and may mediate cell-cell communication, showing promise as non-invasive biomarkers. Our prior work identified donor EV transcripts associated with transplant outcomes and endothelial cell-related transcriptomic changes in brain-dead donors. However, the functional role of these EVs remains unexplored. This study aims to determine whether donor EVs released under brain death conditions actively affect endothelial cells, which form the first barrier between the circulation and the graft. We will incubate donor EVs with endothelial cells and assess their effects on cell viability, barrier integrity, metabolism, and inflammatory signaling using various in vitro assays. This study will clarify whether donor EVs act solely as biomarkers or active mediators in brain death-induced injury. The findings may reveal novel mechanisms of donor injury and ultimately help to develop targeted donor treatment to improve graft quality, increase donor organ utilization, and improve transplant outcomes. |
|
No specific grant area |
4,000 € |
| Ilse |
|
Kaaja |
|
Kaaja Ilse |
Uncovering ERCC6L2 Disease from Germline Defect to Bone Marrow Failure and Leukemia with Transcriptomics and Metabolomics |
Our research group recently identified a Finnish founder mutation in ERCC6L2 gene causing bone marrow failure (BMF) and acute myeloid leukemia (AML). Clinically, ED progresses from BMF due to a germline mutation, to acquisition of somatic TP53 mutations in the bone marrow (BM), and ultimately to therapy-resistant erythroid-predominant acute myeloid leukemia (AML M6), with a median survival of only 10 months. While ERCC6L2 has been implicated in DNA repair and mitochondrial function, the molecular mechanisms driving BMF and leukemogenesis remain poorly understood. This gap is particularly critical as ED currently lacks targeted treatment options. The unique Finnish cohort, comprising nearly half of all known ED patients, offers an unprecedented opportunity to study disease progression. Hematopoietic stem cell transplantation (HSCT) remains the only curative option, but outcomes are significantly worse once AML develops, underscoring the need for early intervention. Furthermore, TP53-mutated myeloid malignancies are notoriously difficult to treat, even without a predisposing germline mutation. Our research focuses on uncovering metabolic and redox mechanisms that impair HSC function and drive progression to AML in ED, with the goal of identifying therapeutic targets beyond HSCT. |
|
Cancer and Cell Based Cancer Research |
4,000 € |
| Ziqi |
|
Kang |
|
Kang Ziqi |
Computational Precision Oncology of Spatial Immune Escape Mechanisms in Ovarian Cancer |
Tumors are complex ecosystems. The highly variable tumor microenvironment (TME) can affect how cancer forms, spreads and responds to treatment (de Visser & Joyce, 2023). Tumor cells have evolved immune escape mechanisms, a primary factor in cancer’s lethality. The project aim is to discover how tumor microenvironment affects the immune escape of ovarian cancer. The research includes up to 600 samples from 400 high-grade serous ovarian cancer (HGSC) patients in the Oncosys-Ova prospective study. The research will (1) profile tumor-immune spatial interactions atlas, (2) identify the transcriptional regulation of immune/tumor cell states that drive immune escape, and (3) integrate single-cell spatial proteomics and transcriptomics from highly multiplexed imaging (t-CyCIF) and in situ spatial transcriptomic technology (Xenium). This project will produce novel computational methods, and the findings will be incorporated with clinical and genetic information, contributing to future therapeutic designs. |
|
Cancer and Cell Based Cancer Research |
4,000 € |
| Timo |
|
Keskinen |
|
Keskinen Timo |
Modeling inborn errors of metabolism and developing clinically applicable gene editing tools using CRISPR base editors |
I study metabolic diseases argininosuccinate lyase deficiency (ASLD), primary hyperoxaluria, propionic acidemia, and methylmalonic acidemia, which are caused by pathogenic mutations that lead to the disruption of normal metabolic processes. Our first objective is to model the disorders, starting from a controlled lab environment and moving subsequently to a more complex mouse model. The second aim is to refine CRISPR base editing tools to correct these mutations efficiently and precisely first in cell models and then directly within living organisms.
The defective enzymes, characteristic of these diseases, are expressed in the liver. To achieve the first objective, we have established protocols to differentiate subject-derived induced pluripotent stem cells into hepatocyte-like cells and created models mimicking the disease conditions. The phenotype tests that we have developed capture the metabolic and biochemical phenotype accurately and precisely. For instance, the key diagnostic metabolite of ASLD, argininosuccinate, showed on average a thousand-fold accumulation in the non-corrected hepatocyte lines in comparison to the corrected and control lines. Regarding the second goal of my research, we have recently generated a mouse model of the Finnish form of ASLD. We first plan to characterize the development of the disease in the mouse and then apply an in vivo base editing therapy delivered within lipid nanoparticles as transiently expressed RNA. |
|
No specific grant area |
4,000 € |
| Henric |
|
Kultalahti |
|
Kultalahti Henric |
Characterization of metabolic heterogeneity in normal pregnancies and gestational diabetes – early-pregnancy prognostic factors |
The burden of metabolic disturbances, such as obesity, fatty liver disease, and type 2 diabetes, is increasing globally. Gestational diabetes mellitus (GDM), a type of diabetes which develops during one's pregnancy, is no exception: increasing number of pregnancies and deliveries are affected by this condition, specifically those with underlying family history of type 2 diabetes. Recent studies suggest that those who develop GDM have substantial phenotypic and genotypic metabolic heterogeneity, and the obstetric and perinatal outcomes in different GDM subtypes vary greatly.
A population-based cohort of 2305 women booking for early-pregnancy sonography at South Karelia Central Hospital, Finland, were invited to participate in the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study in 2013–16. In all, 23% refused, 12% were excluded (e.g. pre-gestational diabetes), and 6% dropped out. Maternal anthropometric parameters (e.g. BMI, waist circumference) were assessed at recruitment at 8–14 weeks’ gestation, and a 75g 2h oral glucose tolerance test was performed at 12–16 weeks' gestation. Serum samples, including fasting insulin, were collected at the same visit as the tolerance test.
The current doctoral study aims to provide insight into the role of fatty liver disease, to investigate the patterns of insulin resistance, and to investigate the cardiovascular adverse outcomes (e.g. gestational hypertension) in pregnancies with and without GDM in a modern obstetric cohort. |
|
No specific grant area |
4,000 € |
| Madeleine |
|
Lackman |
|
Lackman Madeleine |
Endothelial cell adipose depot specificity and its implications for health and metabolic disease |
Adipose tissues (ATs) are key regulators of systemic energy metabolism. While white adipose tissue (WAT) stores energy, brown adipose tissue (BAT) expends energy through thermogenesis. Upon activation, brown adipocytes cleave blood-borne triglycerides into fatty acids and oxidize them in mitochondria, producing heat. Since BAT clears blood triglycerides, increasing its amount could support the treatment of cardiovascular diseases. Considering adipocytes can transdifferentiate from one phenotype to the other, finding a molecular mechanism for WAT-to-BAT conversion could offer a new treatment strategy. Endothelial cells (ECs), that line the inner wall of vessels, can regulate tissue function and cell differentiation by secreting signaling molecules. We and others have found that in obesity, AT vascular density decreases, and brown adipocytes lose their typical morphology and function. We thus hypothesize that AT ECs play a role in adipocyte phenotype regulation. By analyzing EC transcriptomes in mouse WAT and BAT, we have discovered that BAT ECs express a unique set of molecular factors compared to WAT ECs, and that this molecular signature is partly lost upon obesity. Now, I want to study whether these changes can be restored upon weight loss. I will also validate the role of the depot-specific factors in EC phenotype maintenance. Our goal is to find BAT EC-driven signaling pathways that could convert white adipocytes to brown adipocytes to treat cardiometabolic diseases. |
|
Cardiovascular |
4,000 € |
| Oskari |
|
Lehtonen |
|
Lehtonen Oskari |
Advancing Cancer Research through Interpretable AI-driven Image Analysis |
My Ph.D thesis is dedicated to developing interpretable computational methods and AI tools for the quantitative analysis of Hematoxylin and Eosin (H&E) stained whole-slide images (WSIs), the bedrock of histopathology. Built upon widely adopted open-source packages including Cellseg_models.pytorch, Cellseg_gsontools, and Histolytics (over 70,000 downloads collectively around the world), my work enables scalable, reproducible, and histology-grounded discoveries in cancer. This is achieved through advanced nuclei instance segmentation methods, panoptic segmentation methods, and a broad set of spatial analysis tools, allowing for the quantitative extraction of features related to tissues, individual nuclei, cellular neighborhoods, and the extracellular matrix. The project aims to provide researchers across the globe the means to quantify established histopathological biomarkers, identify novel ones, and gain deeper biological insights in a standardized manner. Crucially, these user-friendly tools have already been integrated into numerous cancer research projects within our group and collaborative networks, demonstrating their immediate utility and impact in the scientific community. |
|
No specific grant area |
4,000 € |
| Tuomas |
|
Lumikari |
|
Lumikari Tuomas |
Mobile technology in the detection and treatment of main risk factors of patients with ischemic stroke or transient ischemic attack |
Ischemic stroke is the second-leading cause of death and the third leading cause of
combined death and disability. The risk of recurrent event
is high, as 10% will suffer another attack in 5-year follow-up. Atrial fibrillation (AF) and hypertension are the main treatable risk factors
for ischemic stroke and transient ischemic attack (TIA). Up to two out of three
patients have blood pressure (BP) level higher than suggested to effectively lower
risk for recurrent stroke. Blood-pressure self-monitoring
(BPSM) has been shown to reduce blood pressure levels both in patients with
hypertension and in patients with hypertension and comorbid cardiovascular
disease, but there are few studies on the effect of
BPSM in patients with recent ischemic stroke.
AF is highly prevalent in patients with embolic stroke of undetermined source
(ESUS), but traditional hospital telemetry/holtering
methods to screen for underlying AF are inferior in finding AF compared to
prolonged monitoring.
The aim of this thesis is to address these two key risk factors -undetected atrial
fibrillation and undertreated hypertension to lower the risk of recurrent ischemic
stroke. In Studies I and II we focused on prolonged
cardiac monitoring and AF detection and in Studies III and IV we combine AF screening
to patient-centered treatment of hypertension. |
|
Neurological and Cerebrovascular Disorder |
4,000 € |
| Kaisa |
|
Mäki |
|
Mäki Kaisa |
Pitkittyneet kokemukselliset oireet lievässä aivovammassa: Psykologisten tekijöiden ja elämäntilanteen merkitys |
Suomessa sattuu vuosittain lähes 20 000 lievää aivovammaa, joista merkittävä osa nuorille työikäisille. Lievästä aivovammasta toipuminen vaihtelee. Osa potilaista kokee häiritseviä ja toimintakykyä uhkaavia oireita, kuten väsyvyyttä ja muistivaikeuksia, vielä pitkään vamman jälkeen. Lievän aivovamman suorat fyysiset ominaisuudet, kuten vammaenergia tai mahdolliset kuvantamislöydökset eivät yksin selitä toipumisen vaihtelua. Tässä tutkimuksessa tarkastellaan elämäntapahtumien ja psykologisten tekijöiden yhteyttä työikäisten henkilöiden lievän aivovamman jälkeen kokemiin oireisiin. Lisäksi tutkimme kokemuksellisten kognitiivisten oireiden ja kognitiivisen tehtäväsuoriutumisen välisiä yhteyksiä. Tutkimukseen osallistui 100 lievän aivovamman saanutta 16-68 vuotiasta henkilöä ja 34 nilkkavamman saanutta verrokkia. Tutkimusmenetelminä käytettiin kyselylomakkeita ja neuropsykologisia testejä. Tulokset osoittivat epäoikeudenmukaisuuden kokemusten olevan yhteydessä yleiseen kokemukselliseen oireisuuteen. Viimeaikaisten elämäntapahtumien määrä oli yhteydessä kokemuksellisiin väsyvyys- ja mielialaoireisiin. Kokemukselliset kognitiiviset oireet eivät olleet yhteydessä heikompaan kognitiiviseen tehtäväsuoriutumiseen. Tutkimuksen tulokset lisäävät ymmärrystä lievän aivovamman jälkeisiin kokemukselliseen oireisuuteen vaikuttavista tekijöistä. Tuloksia voidaan hyödyntää lievän aivovamman saaneiden potilaiden kliinisessä arvioinnissa ja yksilöllisten tukitoimien suunnittelussa. |
|
No specific grant area |
4,000 € |
| Anssi |
|
Mykkänen |
|
Mykkänen Anssi |
Genetic variation of pharmacokinetics: studies with
antidiabetic and lipid-lowering drugs |
Large variation exists in drug exposure between individuals, and genetic variation explains part of the variability. This study aims to identify the most important genetic variants influencing the pharmacokinetics of six drugs: simvastatin, atorvastatin, pravastatin, pitavastatin, repaglinide, and gemfibrozil, through a genome-wide association study (GWAS).
We will integrate pharmacokinetic data from clinical trials involving healthy volunteers with genome-wide genotyping data obtained through DNA microarrays. The statin data originate from a novel prospective pharmacogenetic study, while data for repaglinide and gemfibrozil are derived from previous clinical trials conducted at the University of Helsinki's Department of Clinical Pharmacology. Each drug cohort comprises 160-270 participants.
Unlike previous pharmacogenetic research, which often focuses on pre-selected candidate genes and may overlook significant variants, our GWAS approach is hypothesis-free. The robust pharmacokinetic data and substantial sample sizes in this study enable the identification of the most important genetic variants affecting the pharmacokinetics of the investigated drugs.
Identifying genetic variants influencing drug exposure is crucial, as increased exposure correlates with a heightened risk of adverse effects. This research will contribute to more personalized and safer medication use by elucidating the genetic variation of pharmacokinetics. |
|
No specific grant area |
4,000 € |
| Susanna |
|
Nousiainen |
|
Nousiainen Susanna |
Molecular background of endometriosis and the association of endometriosis with cancer |
Endometriosis is a common condition, affecting approximately 10% of women worldwide. It is characterized by the presence of endometrial-like tissue outside the uterus. Although the heritability of endometriosis is estimated at around 50%, its genetic background remains largely unknown. Notably, endometriosis is associated with an increased risk of certain cancers. The two conditions share several biological features, including tissue dissemination, invasion, and angiogenesis.
We investigate the genetic basis of endometriosis and its potential links to cancer through individual-level analyses and population-based approaches. We identified three candidate susceptibility variants for these diseases using next-generation germline sequencing in a family with a likely monogenic predisposition for endometriosis and high-grade serous carcinoma (HGSC). Among these, a variant in FGFR4—a known oncogene—showed the strongest predicted pathogenicity. Additionally, we explore the cancer incidences in a Finnish endometriosis patient cohort (n= 49,912) and in their first-degree relatives (n= 234,684). The Finnish population serves as a reference.
In conclusion, we have revealed a candidate high-risk predisposition variant for endometriosis and HGSC. We will determine the cancer risks of endometriosis patients and their closest relatives. These increase our understanding of the association between endometriosis and cancer, helping to identify individuals at risk. |
|
Cancer and Cell Based Cancer Research |
4,000 € |
| Kirsten |
|
Nowlan |
|
Nowlan Kirsten |
Probing the Molecular and Cellular Mechanisms Behind Thymic Abnormalities in Myasthenia Gravis: Unlocking the Origins of Autoimmunity. |
Ectopic germinal centres (eGCs) in the thymus are central to the pathogenesis of Myasthenia Gravis (MG), a chronic neuromuscular autoimmune disease, as they drive the production of pathogenic anti-acetylcholine receptor autoantibodies. Despite their significance, the molecular and cellular mechanisms sustaining eGCs in MG remain poorly understood.
In this study, we aim to unravel the chronic disturbances in thymic epithelial cells and the dysregulated immune microenvironment that foster eGC formation and maintenance. Using single-cell RNA sequencing, we have comprehensively profiled thymic epithelial cells, follicular helper T cells (Tfh), follicular regulatory T cells (Tfr), and autoreactive B cells in MG patients, comparing these with age- and sex-matched healthy controls to elucidate the molecular perturbations specific to MG. In parallel, we have conducted spatial mapping with cyclic immunofluorescence staining to further characterise the spatial composition, organisation, and cellular interactions within thymic eGCs.
By integrating transcriptomic insights with spatial context, our findings illuminate the cellular and molecular underpinnings of eGC dysfunction, offering fresh perspectives on MG pathophysiology. These insights will not only deepen our understanding of MG pathogenesis but also lay the groundwork for innovative therapeutic strategies aimed at restoring immune balance and mitigating disease progression in MG. |
|
Neurological and Cerebrovascular Disorder |
4,000 € |
| Katri |
|
Rajala |
|
Rajala Katri |
Uudet geneettiset menetelmät ja kuvantaminen luustodysplasioiden sikiödiagnostiikassa – diagnostinen osuvuus ja kliininen merkitys |
Skeletal dysplasias are rare inherited disorders that disrupt the normal bone formation. The most severe forms are associated with significant perinatal morbidity and mortality. In many skeletal diseases there is limited data of the fetal phenotype and the genetic spectrum of these rare disorders differs between populations.
The diagnosis of prenatal-onset skeletal dysplasias mostly relies on ultrasound (US) findings but signs of the disease are often seen rather late and the diagnostic accuracy of prenatal US alone is only 40-68%. In recent years improved genetic methods have expanded prenatal diagnostic options but they are still time-consuming and interpretation of the results is difficult. Other methods as radiography is only available after birth or post mortem. Therefore specific diagnosis may not always be available during pregnancy.
In our study we analyze retrospectively the genetic spectrum of fetal skeletal dysplasias detected in a Finnish tertiary center between January 2013 and March 2020. In this cohort we report the phenotypic details of 36 fetal diseases and evaluate the ability of different diagnostic methods used during pregnancy and after delivery or post mortem.
With this study we reveal new information of these rare skeletal diseases in Finnish population. Evaluating the different diagnostic methods we can improve the diagnostic process and thereby get more information for families about fetal prognosis and risks for future pregnancies. |
|
No specific grant area |
4,000 € |
| Jussi |
|
Salonen |
|
Salonen Jussi |
Tyvisolusyövän ja Bowenin taudin uusia hoitostrategioita |
Ihon tyvisolusyöpä ja okasolusyöpä ovat maailman yleisimpiä syöpiä. Niiden määrä kasvaa räjähdysmäisesti, ja terveydenhuollon resurssien tulisi pystyä vastaamaan tähän kasvavaan määrään tehokkaasti. Tyvisolusyövän erityispiirteistä eri ikäluokissa tarvitaan lisää tietoa. Pinnallisen ja suuren riskin tyvisolusyöpien määrä on kasvussa nuorilla, kun taas iäkkäillä yli 80-vuotiailla nodulaarinen kasvutapa on yleisin. Nuoremmalla iällä tyvisolusyövän sairastaneella tauti vaikuttaisi myös uusiutuvan nopeammin kuin myöhemmällä iällä tyvisolusyöpään sairastuneella.
Pienen riskin kasvainten tunnistaminen on tärkeää, jotta hoitoa voidaan antaa kustannustehokkaasti ei-kirurgisesti. Valtaosa tyvisolusyövistä todetaan iäkkäillä, jolloin hoidossa tulee huomioida potilaan sairaudet ja niiden tuomat riskit, toimintakyky, elämänlaatu ja oma tahto. Valikoiduissa tapauksissa pienen riskin sijainneissa pelkkä seuranta voisi olla yksi hoitolinja.
Uusi mielenkiintoinen ei-kirurginen vaihtoehto tyvisolusyövän ja Bowenin taudin hoidossa on suurienerginen kohdennettu ultraääni HIFU. Ultraääntä voidaan käyttää sekä hyvän- että pahanlaatuisten kasvainten hoidossa ja se on osoittautunut potentiaaliseksi hoitomenetelmäksi myös ihosyövissä. |
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Cancer and Cell Based Cancer Research |
4,000 € |
| Tolou |
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Shadbahr |
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Shadbahr Tolou |
AI-Driven Prognostic Models from Diagnostic Prostate MRI for Metastasis and Mortality Risk Assessment |
Prostate cancer (PCa) is the second most common cancer globally. In Finland, over 5,500 men are diagnosed with PCa annually, and its growing economic burden reflects the aging population. Although 10-year survival rates have improved, treatment responses vary significantly. Current diagnostic tools, prostate-specific Antigen (PSA) screening and transrectal ultrasound (TRUS) guided biopsy, lack specificity and sensitivity, often leading to overdiagnosis and treatment. Our previous research showed that the Prostate Imaging-Reporting Data System (PI-RADS) score is associated with metastasis-free survival and prostate cancer-specific mortality (PCSM). This project investigates whether diagnostic MRI features can be associated with metastasis and PCSM. We hypothesize that MRI at diagnosis time contains signals indicative of disease trajectory. Using over 15,000 PCa diagnostic MRI scans paired with clinical data, including PSA values, biopsy reports, metastasis status, and PCSM collected at Helsinki Uusima Sairalaa (HUS) since 2009, we aim to identify imaging biomarkers for early risk stratification and thus reduce the morbidity in patients with indolent disease. External validation will be conducted using cohorts from Emory University, Tampere University Hospital, and Hospital Claude Huriez in Lille, France. |
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Urological research |
4,000 € |
| Maija |
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Suvanto |
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Suvanto Maija |
Puutiaisvälitteisen Tribeč-viruksen esiintyvyys Etelä-Suomessa |
Orbivirukset leviävät vertaimevien niveljalkaisten kuten puutiaisten välityksellä. Nämä virukset aiheuttavat tautia niin eläimissä kuin ihmisissä. Suomessa orbiviruksia on havaittu viimeksi 1970-luvulla, jolloin vasta-aineita puutiaslevitteistä Tribeč-virusta vastaan havaittiin lehmissä. Tämän jälkeen Tribeč-viruksesta ei ole ollut havaintoja Suomessa. Tribeč-virusta esiintyy Keski- ja Itä-Euroopassa ja se aiheuttaa ihmisissä kuumeista aivotulehdusta. Olemme eristäneet kuolleen räkättirastaan aivoista Tribeč-viruksen. Tällä hetkellä emme tiedä esiintyykö Tribeč-virusta suomalaisissa puutiaisissa ja onko tautitapauksia ihmisissä jo mahdollisesti ollut. Tämän tutkimuksen tavoitteena on seuloa 2000 puutiaista, jotka on kerätty vuosien 2021–2024 aikana Etelä-Suomesta Tribec-viruksen suhteen. Tämän tutkimuksen pohjalta saamme selville kantavatko ja levittävätkö suomalaiset puutiaiset Tribeč-virusta Suomessa. Tämä tutkimus tuo merkittävää tietoa siitä, onko suomalaisissa puutiaisissa uusi zoonoottinen virus kierrossa. Tätä tietoa voidaan hyödyntää diagnostisten laboratorioiden varautumiseen mahdollisiin tautitapauksiin. |
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Borrelia research |
4,000 € |
| Aleksi |
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Tarkkonen |
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Tarkkonen Aleksi |
Neurodegenerative Changes of the Optic Pathway and Progression of Cerebral Small Vessel Disease in Type 1 Diabetes |
Background
Nearly all individuals diagnosed with type 1 diabetes before the age of 30 will develop diabetic eye disease within 20 years of disease onset. The cerebral and retinal microvasculature share several anatomical, physiological, and developmental similarities. Importantly, the retina offers a uniquely accessible window into microvascular health, easily visualized through non-invasive imaging techniques.
Aims
This thesis focuses on cerebral and retinal microvascular disease in individuals with type 1 diabetes and investigates the progression of these pathologies over time. Additionally, we aimed to determine whether radiological signs of cerebral small vessel disease are associated with retinal microvascular caliber and whether retinal microvascular damage extends proximally along the visual pathway, as assessed by measuring the cross-sectional area of the optic chiasm.
Subjects and Methods
This research is part of the ongoing nationwide Finnish Diabetic Nephropathy (FinnDiane) Study. The substudy included 188 adults with type 1 diabetes and 30 age- and sex-matched healthy controls. All participants underwent a baseline clinical assessment, laboratory investigations, brain magnetic resonance imaging (MRI), and retinal imaging. A follow-up MRI was performed after a median interval of 7.5 years. |
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Neurological and Cerebrovascular Disorder |
4,000 € |
| Kirsi |
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Toivanen |
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Toivanen Kirsi |
The therapeutic potential of phosphodiesterase 3A modulators and their synergistic compound combinations in the treatment of soft-tissue sarcomas |
Pehmytkudossarkoomat ovat harvinaisia kasvaimia, joita hoidetaan perinteisesti leikkauksella, usein yhdistettynä sädehoitoon ja/tai kemoterapiaan. Sarkoomien harvinaisuuden ja oireiden moninaisuuden vuoksi diagnoosi saadaan valitettavan usein vasta myöhäisessä vaiheessa, jolloin perinteiset hoitomuodot harvoin johtavat täydelliseen remissioon. Tämän vuoksi sarkoomien hoidossa on suuri tarve kehittää kohdennettuja täsmälääkkeitä.
Väitöskirjatyössäni olen perehtynyt fosfodiesteraasi 3A -proteiiniin (PDE3A) kohdentuviin lääkeaineisiin ja niiden mahdollisuuksiin toimia hoitovaihtoehtoina sarkoomien hoidossa. Tutkimuksissani olen hyödyntänyt sarkoomapotilasnäytteitä ja niihin liittyviä kliinispatologisia tietoja, in vitro -menetelmiä sekä potilasperäisiä sarkoomaeläinmalleja. Kolmen osajulkaisuni keskeiset löydökset ovat:
1. PDE3A on mahdollinen lääkekohde erityisesti myksoidisessa liposarkoomassa ja leiomyosarkoomassa.
2. Tietyt lääkeaineperheet, kuten Bcl-xL-inhibiittorit tehostavat PDE3A:ta kohdentavien lääkkeiden vaikutusta, mikä johti potilasperäisten kasvainten merkittävään pienenemiseen leiomyosarkooma-hiirimallissa.
3. Kehitetty ihon alle annettava lääkevalmiste hidasti PDE3A-täsmälääkkeen vapautumista ja tehosti terapeuttisia vasteita potilasperäisessä sarkooma-hiirimallissa.
Tutkimukseni voi edistää olemassa olevan lääkkeen hyödyntämistä harvinaisten sarkoomien hoidossa ja parantaa täsmähoitomahdollisuuksia sarkoomapotilaille. |
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Cancer and Cell Based Cancer Research |
4,000 € |
| Anna |
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Tuhkuri Matvejeff |
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Tuhkuri Matvejeff Anna |
Hengitysteissä syntyvät partikkelit ja yksilöllisten tekijöiden vaikutus |
Väitöskirjani tavoitteena on luoda syvempää ymmärrystä ihmisen hengitystiepartikkelien tuotosta eri toiminnoissa, kuten puhuessa, yskiessä ja hengittäessä. Lisäksi tutkin, miten yksilölliset anatomiset ja fysiologiset tekijät vaikuttavat partikkelien syntyyn. Tämä on tärkeää, sillä nämä partikkelit voivat kuljettaa mukanaan taudinaiheuttajia ja aiheuttaa tartuntoja päätyessään vastaanottajan limakalvoille esimerkiksi sisäänhengityksen yhteydessä. Erityisen kiinnostavia ovat pienimmät (<5 μm) hiukkaset, jotka voivat kulkeutua suoraan alahengitysteihin, ja jäädä pitkäksi aikaa leijumaan ilmaan. Tällöin niitä voi kumuloitua sisätiloihin, mikä lisää tartuntariskiä erityisesti suljetuissa sisätiloissa.
Yksi väitöskirjani osatöistä analysoi todellisessa kuoroharjoituksessa tapahtunutta superlevitystilannetta, jossa lähes kaikki osallistujat saivat koronavirustartunnan yhden tartuttajan vuoksi, vaikka turvavälejä oli noudatettu. Tapaus havainnollistaa ilmavälitteisen tartuntareitin merkityksen, ja pystyimme myös arvioimaan, millaisista suojatoimista – kuten hengityssuojaimista tai tehokkaammasta ilmanvaihdosta – olisi ollut hyötyä.
Väitöskirjatyöni yhdistää kokeellisia mittauksia, systemaattista kirjallisuuskatsausta ja tietokonemallinnusta. Tulokset lisäävät ymmärrystä ilmavälitteisistä tartunnoista ja tukevat tehokkaiden suojautumiskeinojen kehittämistä tulevia epidemioita ja pandemioita varten. Haen apurahaa väitöskirjatyöni loppuunsaattamiseen. |
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No specific grant area |
4,000 € |
| Anniina |
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Tynjälä |
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Tynjälä Anniina |
Epigenome-wide association study of arterial stiffness in type 1 diabetes |
Type 1 diabetes (T1D), a chronic autoimmune disease characterised by hyperglycaemia, is associated with increased risk for cardiovascular disease and mortality. One proposed underlying mechanism is early vascular ageing manifested as increased arterial stiffness. The pathogenesis of arterial stiffness in T1D is still poorly studied but our recent unpublished analysis supports a moderate role of genetic factors. We further hypothesize that epigenetic changes altering gene expression and cell function are a contributing factor in the pathogenesis. Therefore, we aim to investigate the association of arterial stiffness with methylation levels of single CpG sites across the genome in an epigenome-wide association study (EWAS). The FinnDiane Study is an ongoing nationwide prospective study with clinical patient data comprising more than 5400 well-characterized individuals with T1D, 850 of which with available data on DNA methylation. We will conduct a cross-sectional EWAS with brachial pulse pressure (bPP) as a crude arterial stiffness phenotype and integrate the findings with the genetic data. More specific arterial stiffness phenotypes from applanation tonometry will be used in a smaller population to test whether CpG sites associated with bPP can predict arterial stiffness. The findings may help us understand the risk factors and mechanisms leading to premature arterial stiffness in T1D. |
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Cardiovascular |
4,000 € |
| Erkka |
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Valo |
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Valo Erkka |
The genetics and biomarkers of diabetic kidney disease in individuals with type 1 diabetes |
Diabetic kidney disease (DKD) is a devastating complication of diabetes that affects one-third of individuals with diabetes. However, the pathogenesis of DKD remains poorly understood. This doctoral research focuses on studying biomarkers and genetic variants associated with DKD in individuals with type 1 diabetes (T1D) and is part of the Finnish Diabetic Nephropathy Study (FinnDiane). The doctoral research comprises five projects.
Project 1 aims to identify serum metabolites and peptides predictive of rapid renal function decline beyond traditional risk factors in individuals with T1D. Project 2 investigates the effect of serum sample storage temperature on biomarker stability. Project 3 focuses on identifying urinary peptides indicative of rapid renal function decline in individuals with T1D. Project 4 aims to identify genetic variants associated with urinary metabolite levels through genome-wide meta-analysis and further characterization of identified genetic loci in relation to relevant phenotypes, including kidney function. Project 5 examines the role of rare genetic variants in progression of renal function decline to end-stage kidney disease through gene-based exome array analysis and meta-analysis across participating cohorts.
This research aims to identify novel biomarkers and genetic loci associated with DKD to elucidate pathogenic mechanisms, predict disease progression, and facilitate early therapeutic intervention in high-risk patients. |
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No specific grant area |
4,000 € |
| Enni |
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Vanhanen |
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Vanhanen Enni |
Magneettikuvauksen ja magneettikolangiografian merkitys lapsuusiän primääriä sklerosoivaa kolangiittia sairastavien potilaiden diagnostiikassa, seurannassa ja ennustearviossa |
Primääri sklerosoiva kolangiitti (PSC) on sappiteiden tulehdusta aiheuttava sairaus, joka altistaa maksakirroosille ja sappiteiden syövälle. Magneettikolangiografia (MRCP) on nykyään ensisijainen PSC:n kuvantamismenetelmä invasiivisen sappiteiden tähystyksen (ERCP) sijaan. Tutkimustieto MRCP:n luotettavuudesta sappitiemuutosten vaikeusasteen ja taudin ennusteen arvioinnissa on kuitenkin niukkaa, erityisesti lapsipotilaiden osalta.
Väitöstutkimukseni koostuu kolmesta osatyöstä ja perustuu retrospektiiviseen 68 lapsipotilaan aineistoon. Ensimmäisessä osatyössä arvioimme MRCP:n soveltuvuutta maksanulkoisten sappiteiden merkittävän kaventuman (dominantti striktuura) diagnostiikkaan ja havaitsimme, että ERCP:stä sovelletut kriteerit ovat liian tiukat dominantin striktuuran arvioimiseen MRCP:ssä. Toisessa osatyössä tutkimme MRCP:tä sappitiemuutosten vaikeusasteen arvioinnissa. MRCP osoittautui herkäksi menetelmäksi, mutta arvioi muutosten vaikeusastetta lievemmäksi kuin ERCP, etenkin maksansisäisissä sappiteissä. Kolmannessa osatyössä tutkimme aikuispotilailla kehitettyjen magneettilöydösten pisteytysmallien käyttökelpoisuutta lapsilla. Tulostemme perusteella nämä pisteytysmallit eivät ole luotettavia lasten riskinarviossa. Tutkimuskokonaisuus tuottaa uutta tietoa MRCP:n käyttökelpoisuudesta lapsipotilaiden diagnostiikassa ja seurannassa, ja auttaa kehittämään parempia kriteerejä kliiniseen käyttöön riskiryhmien tunnistamiseksi. |
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No specific grant area |
4,000 € |
| Essi |
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Wallén |
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Wallén Essi |
Effects of alcohol exposure on embryonic and extraembryonic cells in early pregnancy |
The first weeks of pregnancy are a particularly sensitive time in embryonic development to alterations caused by environmental factors. Disruptions during this time can have long-lasting effects on health, but underlying molecular mechanisms are poorly understood. I study one of the most harmful environmental factors, prenatal alcohol exposure (PAE), which can alter developmental programming and contribute to Fetal Alcohol Spectrum Disorders (FASD). I investigate the effects of PAE on both embryonic and extraembryonic tissues during early development. To investigate how alcohol affects embryonic cells, I have exposed human embryonic stem cells to alcohol during their differentiation into the three germ layers, revealing dose-dependent disruptions in gene expression, DNA methylation, and metabolism — most prominently in ectodermal cells. To explore the effects of PAE on extraembryonic cells, I employ cutting-edge techniques, including trophoblast organoids, to reveal epigenetic, transcriptomic, and metabolic alterations in placental cells from gestational weeks 6 to 8. I also compare the findings from early placentas and organoids to full-term placentas to assess the persistence of alcohol-induced changes and evaluate the utility of organoids in toxicological testing. Furthermore, I study the DLK1-DIO3 imprinting control region to deepen our understanding of how PAE affects imprinted genes. The results of this study underscore the sensitivity of early development. |
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No specific grant area |
4,000 € |
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Äikäs Lauri |
The influence of low-density lipoprotein lipidome on the risk of atherosclerosis in humans |
Atherosclerotic cardiovascular disease (ASCVD) arises from the arterial retention and modification of apoB-containing lipoproteins, particularly LDL. While LDL-cholesterol is a major risk factor, recent evidence highlights the role of LDL lipid composition in driving aggregation, proteoglycan binding, and atherogenesis. This PhD project investigates how lipoprotein lipidomes influence ASCVD risk through four complementary clinical studies.
All projects apply our hallmark analyses of LDL aggregation susceptibility and proteoglycan binding combined with advanced lipidomics. In the EPA study, which I organised, we show that omega-3 supplementation remodels VLDL, LDL, and HDL lipidomes, reduces LDL retention, and lowers predicted 10-year ASCVD risk. Results are available as a preprint. In the BLOOD FLOW study, individuals with high cholesterol absorption display increased LDL aggregation susceptibility linked to lipidomic alterations. In the vascular retention study, individuals with T2D exhibit increased vascular proteoglycan binding and increased vascular leakage. The SCAPIS cohort is used to assess LDL aggregation as a predictive biomarker for ASCVD events in general population.
This grant will support the publication of four research papers and enable the finalisation of my PhD thesis. Collectively, these studies aim to cement the role of LDL lipid composition and LDL aggregation susceptibility as risk factors for atherosclerosis, enhancing personalised ASCVD risk prediction. |
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Cardiovascular |
6,000 € |