PROJECT 1: Ovarian Cancer Research: from 'Omics' Data to Pre-clinical Models to Tackle Treatment Resistance MechanismsPI: Jordi BarretinaGroup: Oncology Translational Research A PhD student position is available in the Oncology Translational Research Group at the Institut de Recerca Germans Trias i Pujol, IGTP, under the supervision of Dr. Jordi Barretina and Dr. Arola Fortian to work on an exciting research project investigating treatment resistance in ovarian cancer. This multidisciplinary project focuses on integrating transcriptomic, genomic, and proteomic data to better understand the molecular mechanisms underlying resistance to current therapies. The successful candidate will also play a key role in developing and utilizing advanced preclinical models, including 3D cultures and patient-derived xenografts (PDXs), to test new therapeutic strategies.
Research Objectives:
- Omics Integration: Analyze and integrate high-dimensional transcriptomic, genomic, and proteomic data to uncover key molecular pathways and biomarkers associated with treatment resistance in ovarian cancer.
- Mechanisms of Resistance: Investigate how specific mutations, gene expression profiles, and proteomic alterations contribute to resistance against conventional chemotherapies and targeted therapies.
- Preclinical Model Development: Develop and optimize 3D ovarian cancer cultures and patient-derived xenografts (PDXs) to better mimic the tumor microenvironment and treatment responses in vivo.
- Therapeutic Testing: Utilize the preclinical models to assess the efficacy of novel therapeutic agents or combination therapies designed to overcome treatment resistance.
Key Responsibilities:
- Conduct experiments to ultimately produce and analyze multi-omics data (RNA-seq, whole genome sequencing, proteomics) from patient samples and preclinical models.
- Develop and validate advanced in vitro 3D cancer models and patient-derived xenograft (PDX) models to evaluate therapeutic responses.
- Design and perform experiments to test candidate treatments in both 3D cultures and PDX models, including monitoring drug efficacy, resistance mechanisms, and tumor progression.
- Collaborate with experimental and computational biologists to interpret data and generate new hypotheses for clinical translation.
- Present findings at lab meetings, seminars, and scientific conferences, and publish results in high-impact journals.
PROJECT 2:PI:Cinta FolchGroup: Centre for Epidemiological Studies on HIV/AIDS and STI of Catalonia (CEEISCAT)Contribute to community research applied to public health to improve the health and well-being of gay men, bisexuals, MSM (men who have sex with men), transgender people and other vulnerable populations in Latin America. The selected person will work at CEEISCAT-IGTP, part of the Community Research Hub of Coalition PLUS, a network of community NGOs and academic centres with more than 100 entities around the world. More specifically, CEEISCAT-IGTP co-coordinates the Right PLUS network, which specialises in community research in Latin America.
The main project of the network for the coming years will be the LAMIS-2025 (Latin American MSM Internet Survey), an online survey on the psychosocial and sexual health of MSM, with the aim of generating data to improve public health responses for this population. The 2025 survey aims to achieve participation comparable to 2018, with approximately 65,000 responses, covering topics such as PrEP, DoxyPEP, violence, mental health and migration.
The functions include:
- Methodological support in the management and coordination of community research projects.
- Data analysis, drafting of reports, scientific articles and community return materials.
We are looking for a profile with training in public health or social sciences, with the ability to work with databases and reports, with an interest in working directly with communities affected by HIV, STIs and viral hepatitis, promoting their leadership and involvement in research. Commitment to human rights, sexual diversity and the creation of evidence to design effective and inclusive responses will be valued.
PROJECT 3:
PI: Carolina Armengol
Group: Childhood Liver Oncology (c-LOG)
The Childhood Liver Oncology Group (CLOG) is a young, dynamic, and motivated team committed to advancing our understanding of childhood liver cancer. Our focus is on hepatoblastoma, a rare pediatric tumor whose incidence is increasing globally, underscoring the need for further research to improve diagnosis, treatment, and outcomes.
Hepatoblastoma presents unique challenges due to its low mutational burden, which requires researchers to investigate alternative pathways to understand its development. Studying the tumor microenvironment has emerged as a critical area of research, with potential to uncover therapeutic targets that could lead to innovative treatment strategies.
Key areas of interest include:
- Glycosylation patterns in hepatoblastoma, which may play a crucial role in tumor biology and progression.
- The tumor-associated microbiome, an emerging field with potential implications for therapeutic response and disease development.
The importance of this research is amplified by the limited treatment options currently available for children with advanced or aggressive forms of the disease. Working in this field represents a unique opportunity to contribute to breakthroughs in pediatric oncology.
The candidate will conduct this research within the framework of prestigious projects funded by Horizon Europe (THRIVE) and the Scientific Foundation of the Spanish Association Against Cancer (
www.PMed4HB.eu). A major strength of our group is access to a comprehensive and unique biorepository of patient samples collected from across Europe, from the PHITT international clinical trial (Paediatric Hepatic International Tumour Trial, NCT03017326), offering a unique translational research perspective.
This PhD opportunity also allows candidates to collaborate with an experienced team under the guidance of a Key Opinion Leader (KOL) in hepatoblastoma research, recognized for significant contributions to the field.
PROJECT 4: Immunological spectrum of tuberculosis: new insights into incipient and subclinical disease forms
PI: Irene Latorre
Group: Innovation in Respiratory Infections and Tuberculosis Group
Mycobacterium tuberculosis immune mechanisms involved in protection and progression to disease are still poorly understood.
M. tuberculosis infection is a term that has been evolving, and currently, it is known that encompasses a spectrum of diverse states, which require different diagnostic and treatment approaches. In this sense, our group investigate immune responses within tuberculosis (TB) spectrum, to understand host-pathogen interactions in human and mice models.
Objectives of the research line- To study host systemic and local immune responses on different TB immune states (with special focus on incipient, subclinical and cured TB) to better understand host-pathogen interactions and the established cellular/humoral immune mechanisms.
- To pinpoint the subtleties of the TB spectrum by studying immune response in different experimental mice models with heterogeneous dissemination outcomes.
- To establish an animal model for stratifying host immunity based on the infection with clinical strains isolated from TB patients with different disease severity.
- To evaluate lung immunity in Collaborative Cross (CC) mice (recombinant mice models that represent host heterogeneity) after infection with clinical strains representing subclinical or active disease.
Candidate Profile and Motivations- Interest in the immunology of respiratory infections, with enthusiasm for addressing significant scientific questions in this field.
- Ability to work with mice animal models.
- A strong preference for working in a collaborative, multidisciplinary, and international environment, valuing the exchange of ideas across different areas.
- Good in English, both spoken and written (according to the call), to communicate scientific results, interact with international colleagues, and contribute to publications.
- A proactive attitude and commitment to continuous learning to actively contribute to advancing knowledge in the field.
PROJECT 5:Investigating the interplay between genomics, cell identity and microenvironment, in the formation of malignant peripheral nerve sheath tumors and other neural crest-derived cancersPI: Eduard SerraGroup: Hereditary Cancer Our group studies tumors of the peripheral nervous system (PNS) associated to Neurofibromatosis type 1 (NF1) but also present in the general population as sporadic cases. One of the most problematic tumor types is the malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma with a high metastatic capacity. MPNSTs are most frequently developed in adult patients, but they can develop also in pediatric cases, and currently there is a lack of therapeutic options. NF1 is a genetic disease that affects 1 of 3000 individuals, caused by mutations in the tumor suppressor gene NF1, that confers a predisposition to develop tumors of the PNS. All PNS tumors arise in fact from descendants of embryonic neural crest (NC) cells, pluripotent cells that during development will give rise to many different cell types, like Schwann cells, melanocytes, neurons and other mesenchymal cells. In fact, there are different tumors originating from NC derived cells in addition to MPNSTs, like melanoma, neuroblastoma, pheochromocytoma, etc. Despite a common progenitor, cells of origin of these tumors have different identities, with specific epigenomes and genomic alterations, arising in different body locations.
Our group has developed different types of cell and tissue-based resources, and an extensive genomic repository of tumors and models. In one hand, we specialized in primary cultures and other 3D cultures from primary tumors. In addition, the group has developed different in vitro/in vivo iPSC-derived 3D models, with its differentiation towards NC as a pivotal player. These models bear specific mutations generated by CRISPR editing, and when engrafted in nude mice, develop benign and malignant tumors of the PNS. These 3D models have also been used in high-throughput format for drug screening and different physiological readouts. In addition, the group has generated a large genomic repository of the different tumors and models, including whole genome sequencing, transcriptome, methylome, ATAC-seq and different types of single-cell analysis (scRNA-seq, scATAC-seq, SMART-seq, spatial transcriptomics). The group has participated on the development of a pre-clinical platform of MPNST PDX in collaboration with Dr. Conxi Lázaro at ICO-Idibell, that serves as a pre-clinical platform for precision oncology and personalized medicine. We also have a close collaboration with multidisciplinary clinical expert groups, with patient associations and local and international research groups.
Candidate Profile and Motivations
We are looking for an enthusiastic young investigator interested in interrogating the biological basis of malignant progression of peripheral nerve tumors, and other NC-derived tumors, using primary and iPSC-based 3D cultures. With the aim of understanding the role and interplay of genomic alterations, cell identity and tumor microenvironment, in malignant progression, NC and NC-derived tumors containing different genetic alterations, differentiation stages and tissue contexts, will be analyzed at multiple levels and compared. Fundamental aspects of NC-derived malignancy will be functionally tested and potentially used as therapeutic vulnerabilities.
PROJECT 6:PI: Elisabeth CastellanosGroup: Clinical Genomics Unit (UGC)The use of gene panels is now part of the diagnostic routine in most clinical settings, as it enables the study of multiple genes at the same time and has proven to be more cost-effective (PMID: 25940718, 26205736). Although the use of panels has led to an increase in the number of cases in which a causal pathogenic variant is identified (PMID: 25452441, 25559809, 24733792, 26022348, 26976419), there are still some challenges. On the one hand, the number of identified genetic variants has increased considerably, many of them being variants of uncertain significance (VSI), often very difficult to interpret their contribution to the development of the patient's clinical manifestations. In addition, there is a high percentage of patients in whom no clearly pathogenic genetic variant is identified. This may be due to the existence of other genes not included in the different panels analysed, but it may also be cases in which the causal variant has not been identified in the techniques currently used (gene panels or whole exome sequencing (WES)).
Several studies published in the early 2000s showed that mutational analysis from RNA (cDNA) identified pathogenic variants that had not previously been described from DNA, and that these were not only variants located in the canonical splicing residues (PMID: 10607834, among others). To date, different variants that alter splicing have been described in several of the genes included in our I2HCP panel (PMID: 23534816, 30472649). However, most laboratories continue to perform genetic studies using DNA due to its greater simplicity.
Specifically, this project is key to developing new diagnostic tools that reduce the technological limitations of genetic diagnosis using DNA-based techniques (panels, WES), such as the impossibility of detecting variants that affect splicing or variants located in unanalysed regions (deep intronic), or the difficulty of classifying certain variants when their effect at the RNA level is unknown.
In recent years, with the aim of improving the genetic diagnosis of patients with suspected hereditary cancer, several research groups have implemented the use of RNAseq platforms. RNAseq technology has classically been employed at the whole transcriptome level but can also be adapted to a part of the transcriptome (PMID: 19835606). Targeted RNAseq generates a greater wealth of information than genomic sequencing, providing multiple levels of knowledge: relative expression levels, discovery of new splicing variants, detection of new fusion transcripts and distinct isoforms (reviewed in PMID: 26996076). In addition, it allows the analysis of transcriptional events at a greater depth than the study of the whole transcriptome (PMID: 19015660, 21191423), as enrichment with specific probes facilitates the detection of rare mRNA isoforms (PMID: 19835606, 22081020), while facilitating the interpretation of detected variants and minimising incidental findings in unrelated genes.
More recently, a new approach has emerged that consists of sequencing long reads (several kb in length), led commercially by Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT). This system detects thousands of isoforms generated by alternative or aberrant splicing, with greater reliability than short read techniques. In addition, it facilitates specific alignment with the reference genome, as it is able to read through complex repetitive or homologous regions, areas more susceptible to false positives and false negatives in conventional sequencing based on short reads.
The main objective of this project is to improve the clinical applicability of the use of panels. To this end, we propose to implement new methodologies and develop new tools useful for the diagnostic community for the benefit of patients with hereditary diseases with a predisposition to develop tumours, including Neurofibromatosis, Schwannomatosis, hereditary breast and ovarian cancer, Lynch syndrome, etc. More specifically, for this project we intend to add long fragment sequencing on an ONT platform to complement our NGS panel with cDNA analysis, and thus detect mutations affecting splicing not identified in the previous analysis, quantify transcripts, detect possible differential allelic expression differences (ASE), and refine the classification of some variants of unknown significance (VSD), if they prove to have an effect on the correct splicing of the gene. Unfortunately, there is no commercial protocol for long fragment sequencing of RNA-generated libraries on a MinION platform to select transcripts from a range of genes of interest using custom capture probes. Therefore, the development of our objective is a great challenge, both in terms of the design of a protocol that meets our needs, as well as the subsequent bioinformatics analysis of the data obtained by RNAseq.
The proposed project will address some of the main limitations of current diagnostic algorithms. It is expected that the results of the project will improve the classification of VSDs, thanks to the implementation of a new technology that will assess the effect of these variants at the RNA level. In addition, we estimate that a proportion of patients with different types of hereditary cancer without identified pathogenic variants will be found to have the underlying cause, thanks to the analysis of genomic regions not included in current panel studies. The new methodological approach will provide a new source of information, complementary to that routinely obtained in DNA panel studies, thus optimising the interpretation of molecular results, and increasing the clinical relevance and diagnostic utility.
Our ultimate goal is to improve the management, prevention and treatment of different hereditary cancers, areas in which we are a reference thanks to the Spanish reference centre (CSUR) in Phakomatosis and the ERN GENTURIS (European Reference Network for all patients with one of the rare genetic tumour risk syndromes) of which we are an active member. The project will focus on patients diagnosed with cancer and their healthy relatives with an increased risk of developing it. This research is by definition focused on the search for a direct impact on patient care, as it will optimise the identification of those who can benefit from preventive measures.
PROJECT 7: Targeting Tumor Microenvironment to Enhance Lymphocytic Infiltration in Colorectal CancerPI:Sergio AlonsoGroup: Cancer Genetics and EpigeneticsImmunotherapies, which encompass several strategies to enhance the patient's immune system to attack cancer cells, have made extraordinary progress over the past decade, revolutionizing the treatment of many cancers. The immune system constantly surveys the body and can detect and kill cancer cells. However, cancer cells often overexpress surface proteins known as immune checkpoint ligands, which serve as a defense against immune cells.
One of the most advanced immunotherapy strategies involves using immune checkpoint inhibitors (ICIs) to release T-cell action against cancer cells. These therapies have been extraordinarily effective against several types of cancer. However, most sporadic colorectal cancers (CRCs) are poorly immunogenic and do not respond to ICI therapies. Increasing the immunogenicity (the recognition of tumor cells by immune cells) in these tumors could improve their response to ICI therapy.
Using genome-wide epigenomic profiling in over 80 primary CRCs, we have identified that epigenetic silencing of certain extracellular matrix remodelers, which are involved in shaping the tumor microenvironment, is associated with higher lymphocyte infiltration in CRC. In this PhD project, the candidate will investigate the role of the epigenetic downregulation of these extracellular matrix remodelers on immunogenicity in primary CRCs and other gastrointestinal cancers (primarily stomach adenocarcinomas). The candidate will explore the underlying mechanisms using novel in vitro 3D co-culture models incorporating cancer cells, fibroblasts, and lymphocytes. The goal is to identify novel therapeutic targets to enhance gastrointestinal cancer immunogenicity and improve the response to ICI therapies.
Experimental Approach
The PhD candidate will employ a variety of molecular and cellular biology techniques, including PCR, qPCR, RT-qPCR, sequencing, bisulfite sequencing, western blotting, cell culture (2D and 3D), microscopy, cell cytometry, among others. The project also involves computational approaches (using R and/or Python),including methylation/gene expression microarray analysis, whole-exome sequencing (WES), database mining (TCGA, ICGC), and linear/logistic models, among others.
The aim of the project is to validate the initial findings in additional CRC cohorts, analyze whether these observations extend to other tumor types, and explore the mechanisms underlying the association between epigenetic silencing of extracellular matrix remodelers and higher immunogenicity. Depending on the results obtained in cellular models, we will consider extending the investigation to more complex preclinical models (patient-derived xenografts in mice) in the CMCiB facilities.
PROJECT 8: Neurofibromatosis Type 1 (NF1) PI: Bernat GelGroup: Translational Genomics and Bioinformatics of Cancer
Neurofibromatosis Type 1 (NF1) is a genetic cancer predisposition syndrome caused by the heterozygous inactivation of the NF1 gene, affecting approximately 1 in 3,000 people. Among its many manifestations, peripheral nervous system tumors pose the greatest threat to NF1 patients. Most individuals develop dozens to hundreds of small skin tumors called cutaneous neurofibromas (cNF). About half of them also develop one or more larger benign tumors, called plexiform neurofibromas (pNF), which can transform into premalignant atypical neurofibromas (aNF) and eventually progress to malignant peripheral nerve sheath tumors (MPNST). MPNSTs are aggressive soft-tissue sarcomas with limited treatment options beyond surgery and a poor prognosis. Their high metastatic potential makes early detection critical for improving survival. MPNSTs are the leading cause of NF1-related mortality and NF1 individuals have a ~12% lifetime risk of developing one.
The candidate will lead one of our projects such as integrating multi-modal single-cell data to uncover cellular composition, states and origins of NF1-associated tumors; developing automated pipelines for nanopore DNA sequencing in clinical diagnostics; or designing the analysis of cfDNA sequenced with nanopore for early cancer detection and tissue-of-origin identification. They will also collaborate on other projects and actively contribute to project design, funding acquisition, data generation, and analysis, gaining comprehensive experience in translational research.
The Translational Genomics and Bioinformatics of Cancer group is focused on applying genomics and bioinformatics tools to rare and understudied tumors such as sarcomas and pediatric cancers. Our long-term objective is to help transition these technologies into the healthcare routine so rare cancer patients can get the best management and treatment possible.
PROJECT 9: PI: Teresa Gasull
Group:Cellular and Molecular Neurobiology (CMN)
The PhD student’s research project will be conducted within the Cellular and Molecular Neurobiology (CMN) group, which focuses on uncovering the pathological mechanisms in the brain associated with neurovascular disorders, particularly stroke. Stroke represents a critical global health challenge, affecting 15 million people annually, with fewer than 15% of patients achieving full recovery. This research aims to address this unmet need by exploring novel approaches that have the potential to significantly improve stroke outcomes.
As part of the project, an innovative treatment will be tested in a large animal stroke model with brain architectures closely resembling those of humans. These experiments will be carried out at the Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), a state-of-the-art preclinical research facility specifically designed to support biomedical investigations. This essential preclinical trial step is pivotal for transitioning to clinical trials in stroke patients.
The project’s specific objectives include:
- Biomarker Discovery: Identifying innovative biochemical and imaging biomarkers in the animal model to enhance stroke type identification, patient stratification, treatment allocation, and outcome prediction.
- Mechanisms of Cell Death: Investigating novel mechanisms of cell death to pinpoint therapeutic targets for stroke and other neurovascular disorders.
- Innovative Stroke Models: Developing advanced models to study white matter damage and brain connectivity through multimodal MRI imaging, providing insights into human-like brain responses.
Pursuing a PhD within this group offers an exceptional opportunity due to its multidisciplinary approach, cutting-edge methodologies in neurobiology, and focus on translational research. The integration of experimental modeling, biomarker discovery, and computational tools provides a robust platform for making impactful contributions to stroke diagnosis and therapy.
The PhD work will encompass tasks within the following two projects:
- Innovative Biomarkers to Diagnose Ischemic Stroke: The Bet on miRNAs in Extracellular Vesicles in Humanized Swine Models (IBIDI-Stroke)
REF: FIS PI21/01925-extended - Last Step to the Clinic: Randomized Preclinical Study of Intravenous Apotransferrin in the Treatment of Acute Ischemic Stroke
REF: SLT036/24/000048
PROJECT 10: Developing epigenetic diagnostics and therapeutics for thyroid cancer PI: Mireia JordàGroup: Endocrine TumorsWe are seeking an INPhINIT fellowship awardee for developing her/his PhD thesis on the project “Developing epigenetic diagnostics and therapeutics for thyroid cancer”, with a high level of enthusiasm and motivation, strong sense of responsibility and initiative.
The “Endocrine Tumors” group, led by Dr. Mireia Jordà, focuses its research on answering major clinical questions that are yet to be resolved. The research project in which the successful candidate will work will focus on epigenetics and personalized medicine in aggressive differentiated thyroid cancer (DTC). The main rationale is that a better understanding of the molecular landscape of DTC will improve the management of DTC patients. The ultimate goal is to translate the findings to clinical practice. In other areas of medicine there has been a conscious clinical move towards personalizing treatment; however, this trend has just begun to take hold in the management of DTC.
Project summary
Most patients with DTC have a favorable prognosis; however, those who develop distant metastases or become refractory to standard radioiodine (RAI) treatment—sometimes years after diagnosis—face a poorer prognosis and reduced survival. These cases exhibit heterogeneous behavior, but current biomarkers for predicting disease progression remain limited. Additionally, therapeutic options for patients unresponsive to RAI are scarce, with multikinase inhibitors (MKIs) being the only approved treatments. Unfortunately, nearly all patients eventually develop primary or acquired resistance to MKIs, and the mechanisms driving this resistance are not yet fully understood.
Most studies on aggressive TC are confined to genomic and trasncriptomic alterations, while there is a lack of epigenomic studies. Recently we reported an increased global DNA hypomethylation in aggressive thyroid cancer associated with progression and dedifferentiation. Furthermore, we have identified distinct DNA methylation changes in the primary tumor at the time of surgery that may help predict the risk of distant metastasis, RAI refractoriness, and response to MKIs, enabling personalized treatment strategies for DTC patients. We aim to validate our epigenetic biomarkers in preoperative samples obtained via fine needle aspiration (FNA) biopsy for early prognosis. Additionally, we will assess circulating extracellular vesicles (EVs), particularly EV-DNA methylation, as non-invasive prognostic biomarkers and explore their potential as a liquid biopsy tool in DTC (proof-of-concept). Furthermore, we will characterize the transcriptome of metastatic and RAI-refractory DTC, integrating this data with existing DNA methylomes to gain deeper insights into the mechanisms driving metastasis, RAI refractoriness, and resistance to MKIs, as well as to identify potential cellular vulnerabilities. Functional validation of these therapeutic targets will be conducted using cell lines and patient-derived preclinical models.
Our research is expected to identify epigenetic biomarkers for early prediction of distant metastasis and disease monitoring in DTC patients, ultimately enhancing patient management, quality of life, and survival. Moreover, our integrative multi-omics approach will provide valuable insights into the biology of metastasis and drug resistance in thyroid cancer, paving the way for novel therapeutic strategies. This is a translational project and will be done in close collaboration with physicians.
The project will involve the use of multiple approaches including molecular biology, human samples, cell culture (cell lines, patient-derived preclinical models), CRISPR-Cas9 genome editing, isolation of EVs, multi-omics approaches (RNAseq, DNA methylation arrays), and bioinformatic analyses. Additionally, the candidate will have to write the resulting manuscripts, present results in internal and external seminars, and contribute to the supervision of junior members of the team.
PROJECT 11: PI: Maria Rosa SarriasGroup: Translational cancer immunologyThe goal of this PhD thesis is to expand our understanding of TAM biology, contribute to the development of our immunotherapy by elucidating its full mechanism of action and possibilities, and ultimately advance the development of a novel cancer treatment. A distinctive feature of this position is the opportunity for the PhD student to work in close collaboration with TAM Therapeutics, our spin-off dedicated to the regulatory, clinical and commercial development of this research. This synergistic relationship will provide the candidate with invaluable insights into the translational aspects of scientific discovery, bridging the gap between academia and industry.
The candidate will thus not only gain expertise in cutting-edge research but also acquire knowledge and skills essential for the practical application of findings in preclinical and clinical settings, significantly enriching their academic and professional development.
MAIN RESPONSIBILITIES
- Conduct in vitro functional and phenotypic analysis of macrophages and immune cells in the context of cancer using primary cells and cell lines.
- Participate in the execution of preclinical cancer models in mice and sample analysis.
- Investigate biomarker expression in human samples employing techniques such as immunohistochemistry, immunofluorescence, or RT-PCR-Sequencing.
- Maintain a comprehensive understanding of the research field through literature review.
- Analyze and interpret experimental data, contributing to manuscript preparation.
- Actively participate in laboratory meetings, IGTP seminars, and national/international conferences.
PROJECT 12: PI: Katrin BayerGroup: Genomics and Transcriptomics of SynucleinopathiesSynucleinopathies are characterized by abnormal alpha-synuclein oligomerization and aggregation. Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases where aggregated alpha-synuclein deposits as Lewy bodies. Whereas PD is the most common movement disorder, DLB is the second most common cause of dementia after Alzheimer's disease (AD). DLB also shows an important neuropathological overlap with AD difficulting its clinical diagnosis. Therefore, we have been working on the identification of peripheral biomarkers as diagnostic tools for DLB, and have identified platelet-derived miRNAs which differentiate DLB from AD. Platelet miRNAs are diminished in DLB and lead to profound transcriptomic changes and a pre-activation state. Thus, our goal is to understand how platelets contribute to disease development, and our objectives are:
- Determine the mainly affected pathways during abnormal platelet activation in DLB
- Analyze platelet activation related immunoreceptor profiles by flow cytometry and platelet interaction with immune cells (CD4+, CD8+ T-lymphocytes, B-lymphocytes, monocytes) using CytPix
- Analyze mitochondrial function by DNA quantification and cybrid generation
- Analyze the effect of disease-derived platelets on neurons (cell line SH-SY5Y), in microglia (cell line HMC3)
- Establish a blood-brain-barrier cell model for testing the effects of diseased platelets and their content on permeability and integrity.
Our research has a strong translational character, and so, our final aim is to translate research results from post-mortem brain tissue to peripheral tissues. So far, we have identified four biomarkers and have patented all of them. Two are specific for DLB subgroups, whereas the other two may serve as an early diagnostic marker of DLB.
Since neuropathological changes start up to 20 years before clinical symptoms of either PD or DLB become evident, we are currently extending our research to prodromal phases of Lewy body disorders.
The Genomics and Transcriptomics of Synucleinopathies (GTS) group at the IGTP offers a PhD position to perform translational research on Lewy body disorders in the context of two research projects. These are related to miRNA-based biomarker development, and the candidate will participate in the validation of early biomarkers for dementia with Lewy bodies. Research will include reaching a molecular and cellular understanding of mechanisms of action, with special emphasis on signal transduction involved in brain targeting. The role of these specific miRNAs in preclinical stages of disease development will be also addressed.
