Tuesday, 17 October 2023

Nikola Maria de Lange - Workshop 1


After building a strong mathematical foundation during my bachelors training in applied mathematics, I was curious about biological and medical application. As a result, I decided to pursue the Master in Integrated Systems Biology instead of continuing with mathematics. During my masters training I gained valuable insight into biological processes.
The combination of applied mathematics with the training in systems biology and through this the experience in different research areas made me an open person to many different topics in science.
My research project during my bachelor thesis provides experience with time series analysis. The project revolved around two complexity measures based on the correlation integral, namely approximate entropy and sample entropy. During my bachelor thesis I implemented the sample entropy in MatLab as brute force algorithm and as k-d-tree and compared the efficiency of both algorithms.
During my student job in Thomas Sauter’s group I gained experience in working with MatLab code written by other researchers by implementing a non-linear function in the FALCON toolbox. Thus, I am able to understand and adapt to code of different origins.
My masters training made me realize that it is a strong asset to use my mathematical background to approach complex research topics.
As part of the PARK-QC doctoral training unit I focus on the development of bioinformatics tools and pipelines for the analysis of heterogenous biomedical data in Parkinson’s disease context. During the course of my PhD I implemented a multi-omics approach combining ATAC-seq and RNA-seq for the inference of gene regulatory networks to identify top regulators in cell differentiation processes.


Introduction to workflow management systems – building a bioinformatics pipeline with Snakemake


Bioinformatic analyses often require a variety of heterogeneous software in various stage of maturity to process the high-dimensional and complex omics data. Given the large volume of data produced, high performance computing resources are often necessary to conduct such analyses. A complete analysis workflow requires several bioinformatics tools that differ in execution environments as well as CPU and memory requirements. Using separate scripts for each step in a pipeline and manual intervention for data management is laborious and error-prone.

Workflow management systems such as Snakemake have become invaluable for resource-efficient computational analyses. Snakemake, Nextflow and BigDataScript provide an easy-to-develop and easy-to-use framework, while other pipeline framworks have an advantage in performance.

In the context of this workshop the participants will get an overview of workflow management systems and their application in the bioinformatics context. After a short introduction to the basic syntax of Snakemake, the participants will get the opportunity to write a short Snakemake pipeline using down sampled data to gain firsthand experience with a workflow management system.

Saman Maleki - Workshop 2


Dr. Maleki’s research is focused on sensitizing tumors to immunotherapy and translating promising pre-clinical immunotherapy studies into human phase I trials by working with clinicians and industry partners. Dr. Maleki has over 10 years of experience in translational cancer immunotherapy, onco-microbiome, drug development, biomarker development, and phase I clinical trials in oncology.


Therapeutic modulation of the gut microbiome in oncology settings


The gut microbiome is exceedingly recognized for its role in supporting the anti-tumor functions of the immune system and response to immunotherapy with immune checkpoint inhibitors (ICIs). Recently, microbiome-modifying strategies are being explored for combination treatment with ICIs in different cancers. One strategy to modify a cancer patient’s microbiome is to use fecal microbiota transplantation (FMT) either from a treatment responder patient or a healthy donor. Both strategies have shown promising results in successfully changing melanoma patients’ gut microbiome and potentially conferring treatment response to ICIs.

We have shown that combining FMT from healthy donors to anti-programmed cell death-1 (PD-1) immunotherapy is safe in the first-line setting in advanced melanoma patients and associated with improved clinical response. In our study, patients who experienced a successful donor microbiome engraftment and retention, determined by longitudinal metagenomics shotgun sequencing and 16s rRNA gene sequencing, became responders to anti-PD-1 therapy. These patients also experienced changes in their metabolite profile measured in plasma including increase of histidine post FMT that was stable overtime. We have also observed enrichment of certain immunogenic bacteria in these patients post FMT such as Ruminococcaceae SGB15234 and SGB14909, Alistipes communis, and Blautia SGB4831. Conversely, non-responder patients had an overrepresentation of Enterocloster asparagiformis and Catabacter hongkongensis. We have also observed an increase in ICOS+ CD8+ T-cells in the peripheral blood of responders indicating of the activation of the immune system post FMT and anti-PD-1 combination therapy. Avatar mouse models colonized with patients’ stool confirmed the role of donor FMT in driving response to anti-PD-1 therapy in advanced melanoma patients.

Our results indicate that FMT from healthy donors is safe in the first-line setting in melanoma and can potentially improve clinical response. We are now testing combination of FMT with immunotherapy in lung cancer, melanoma, and renal cell carcinoma. We are also combining healthy donor FMT to chemotherapy in pancreatic cancer and to neoadjuvant chemoimmunotherapy in triple-negative breast cancer. More clinical and translational studies are required to further support the role of microbiome interventions in oncology.


Wednesday, 18 October 2023

Alba Maiques-Diaz - Workshop 3


Past projects:
We identified that the pro-differentiation effect of LSD1 inhibition is independent of its catalytic activity: it is the result of inducting the displacement of LSD1 from the transcriptional repressor GFI1, which leads to increased activation of GFI1-bound prime enhancers through acetylation with consequent increased expression of nearby genes (Maiques-Diaz et al, Cell Reports, 2018).

Current project:
Chronic lymphocytic leukemia (CLL) is one of the most frequent blood cancers. ). It is characterized by the accumulation of neoplastic B cells in the blood, bone marrow and lymphoid tissues. CLL is genetically heterogeneous, and CLL initiation events are still poorly defined. Genome-wide sequencing efforts identified frequently mutated genes (e.g. NOTCH1, SF3B1 and MYD88) and structural alterations (e.g. tris(12), del(13q) and del(11q))4. However, they are shared by only 5-15% of patients and, even more, some patients do not exhibit any genetic lesions with putative driver potential.

In contrast to CLL´s genetic heterogeneity, Dr. Martin-Subero´s group at IDIBAPS has revealed that CLL cells share a common chromatin activation signature distinct from normal B cells (Beekman, Nat Genet 2018). This de novo active chromatin signature is even shared between the two clinic-biological subtypes of CLL. My overall aim is to disentangle the factors that drive this unique CLL enhancer repertoire activation, to help to define novel therapeutic targets.

Bio taken from LinkedIn

Development of in vitro tools to study mature B cell malignancies using patient samples.


The landscape of the genomic, epigenomic and transcriptional features from patients with B-cell lymphomas has been described in several pivotal sequencing studies. These included chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), two lymphoid neoplasms characterized by the proliferation and accumulation of mature small CD5+ B cells. CLL is considered an indolent disease, whereas the clinical course of the majority of MCL patients is aggressive. However, the clinical evolution of both malignancies is very heterogeneous. While the prognostic significance of some of the described genomic and epigenomic alterations is known, their specific contributions to disease pathogenesis remains largely unexplored. Attempts to address this experimentally using CLL and MCL primary cells have encountered several challenges, mostly owing to the importance of the tumour microenvironment factors for the survival and proliferation of the malignant B cells. Thus, most experimental settings used include genetically modified mouse models for CLLor xenograft models for MCL, and human cell lines which have numerous discrepancies with human primary cells limiting the conclusions that can be draw from such experiments. Importantly, these model systems mostly recapitulate the more aggressive forms of both neoplasms, but they are not appropriate tools for studying the indolent subtypes of the disease. Thus, there is a need to directly apply molecular methods, such as stable gene transduction and CRISPR-Cas9 genome editing, in primary malignant B cells as they preserve the clinico-biological spectrum of CLL and MCL. To overcome these limitations, we have developed a method that permits gene transfer with high transduction efficacy and minimal toxicity, which allows the functional investigations of genes recurrently mutated in primary malignant B cells. We employed this technique to interrogate the molecular functions of NOTCH1 and NOTCH2, which are two of the most commonly mutated genes in B-cell lymphomas1. Moreover, we have established a robust method for CRISPR-Cas9 editing of patient derived CLL and MCL cells2. With it we have shown a permanent protein depletion that is maintained in any offspring cell enabling longer follow up of downstream analyses, even targeting several candidate genes simultaneously. Importantly, these methods permit to deepen into CLL and MCL biological complexity using directly primary samples, overcoming the current dependency on cell lines and murine models.

Rejko Krüger - Workshop 4


Rejko Krüger is Professor for Clinical and Experimental Neuroscience at the University of Luxembourg and Director of Transversal Translational Medicine at the Luxembourg Institute of Health. His work is supported by an Excellence Award for Research in Luxembourg of the Fonds National de Recherche (FNR; PEARL). Since June 2019 he links between the Luxembourg Institute of Health (LIH) and the Luxembourg Centre for Systems Biomedicine (LCSB) to contribute to personalised medicine by implementing translational research programmes involving partners from different fields within a joint scientific strategy.

Within his position Rejko Krüger integrates expertise in (i) fundamental research on neurodegeneration ( and (ii) clinical research as Coordinator of the National Centre of Excellence in Research on Parkinson’s disease (NCER-PD; funded by the FNR.

Research interests focus on the elucidation of molecular signalling pathways underlying common neurodegenerative diseases using patient-based cellular models. A unique fully automated platform for high content-/ high throughput-screening of drugs on stem-cell derived neurons has been established to identify neuroprotective compounds for precision medicine (

His clinical and research experience extends over more than 20 years and resulted in more than 150 scientific publications (>33.000 citations; H Factor 64).

In 2018 he launched new concepts for integrative care on neurodegenerative diseases in Luxembourg, including Parkinson’s disease ( and the prevention of dementia (


Clinicogenetic stratification to enable precision medicine in Parkinson’s disease

Neurodegenerative diseases like Parkinson’s disease (PD) represent a major burden for people worldwide and still no curative treatments are available. Trials aiming at discovering neuroprotective treatments failed, because they did not account for the clinical and pathophysiological heterogeneity of PD. Genetics of PD provided first insight into the complex mechanisms underlying this fastest growing neurodegenerative disease and enable first neuroprotective treatments. Based on genetic stratification and advanced cellular modelling using patient-based induced pluripotent stem cells (iPSC), important mechanisms of neurodegeneration were deciphered, that define first entry points to develop disease-modifying compounds for more targeted therapies. Together with novel biomarkers that for the first time allow a reliable diagnosis of PD and support a biological staging of the neurodegenerative process, novel strategies for early detection and clinical decision support. This translates into the increasing importance of high quality data related to people with PD and individuals at risk to develop neurodegeneration to define novel markers for target engagement and therapeutic outcomes. This now starts to be translated into novel strategies, not only better treatments, but – even more important – for first steps into precision prevention to decrease the impact of neurodegenerative diseases on our ageing societies.