The doctoral dissertation in the field of Computational Biology will be examined at the Faculty of Health Sciences. The public examination will be streamed online.
What is the topic of your doctoral research? Why is it important to study the topic?
My doctoral research focuses on using transcriptomics to better understand the molecular basis of complex diseases and improve treatments. Transcriptomics allows for a detailed analysis of gene expression across tissues, helping us see how diseases develop and progress at the cellular level.
The first study addresses ischemic heart disease (IHD) and heart failure (HF), both leading causes of death worldwide. Despite extensive research, detailed mechanistic basis of these diseases remains uncertain, limiting treatment options and often leaving disease progression unchecked.
The second study focuses on the shortage of donor organs for heart transplants. Xenotransplantation, using genetically modified pig hearts, offers a potential solution, but early immune rejection remains a major challenge. Understanding how the human immune system reacts to these transplants is key to improving their success.
Finally, the third study explores Pityriasis Rubra Pilaris (PRP), a rare inflammatory skin disorder. Current treatments are neither efficient nor disease-specific, with many patients showing limited improvement. By studying its molecular drivers, we sought to discover better treatments.
What are the key findings or observations of your doctoral research?
In IHD and HF, we discovered and characterised widespread inflammation and changes in heart blood vessels in the right atrium. We emphasise that IHD and HF involves more than the left ventricle. Our molecular characterisation of the diseases processes open new possibilities for targeted therapies aimed at the heart's microvasculature.
In xenotransplantation, we observed early immune reactions and metabolic stress in two recipients of genetically modified pig hearts, and deeply characterised the two recipients’ responses. This highlights the need for better immunosuppressive treatments and proper organ size matching to improve transplant outcomes.
For Pityriasis Rubra Pilaris (PRP), we identified the IL-1β inflammatory pathway as a key driver of the disease. Blocking this pathway with IL-1 antagonists led to successful treatment, offering a new option for PRP patients who currently have limited therapies.
Across all three studies, we produced comprehensive transcriptomic maps that reveal how cells and tissues behave under these conditions. These datasets will be valuable for future research, offering a resource to validate new hypotheses and develop better treatments.
How can the results of your doctoral research be utilised in practice?
In cardiovascular medicine, identifying gene expression changes in the heart's microvasculature provides new therapeutic targets that could help slow or prevent heart failure and IHD progression. Our findings support more personalised treatment approaches for heart patients.
In xenotransplantation, understanding the immune and metabolic reactions in human recipients can help refine immunosuppressive protocols and improve the success of pig-to-human heart transplants. This is a critical step in addressing the global shortage of donor organs and saving more lives.
For Pityriasis Rubra Pilaris (PRP), targeting the IL-1β pathway with IL-1 antagonists offers a new, more effective treatment option. This approach needs to be further validated with wider patient cohorts, potentially improving care for this serious disease. In addition, our detailed molecular mechanism characterisation could be used to identify and test other targets.
What are the key research methods and materials used in your doctoral research?
We used advanced transcriptomic techniques, including single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics (ST), to analyse gene expression at a detailed level across different tissues. These methods allowed me to investigate disease mechanisms at the cellular level, uncovering molecular drivers in various conditions.
For cardiovascular disease, I analysed tissue from patients with ischemic heart disease and heart failure, in the heart right atrium, examining how gene expression changes across disease status. In xenotransplantation, we employed multi-omics approaches, in addition to snRNA-seq and ST, to study early immune responses to genetically modified pig hearts in human decedent recipients. For Pityriasis Rubra Pilaris (PRP), pathway analysis was employed to identify key inflammatory drivers and test our discovered target.
The doctoral dissertation of Eloi Schmauch, MSc, entitled Transcriptomics for translational medicine: Study of RNA expression in cardiac diseases and auto-immunity will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Dr Sikander Hayat of Uniklinik RWTH Aachen, and the Custos will be Professor Minna Kaikkonen-Määttä of the University of Eastern Finland. The public examination will be held in English.
For further information, please contact:
Eloi Schmauch, MSc, eloi.schmauch@uef.fi, https://uefconnect.uef.fi/en/person/eloi.schmauch/
