Host Research Groups
You have the possibility to join one of the groups listed below
Overall research theme(s)
Hepatobiliary cancers are a dismal group of diseases, which often is diagnosed at late stages where the tumor is locally advanced, metastatic and, as a result, is associated with low resectability.
In the Andersen group, it’s our goal to understand the pathogenesis and molecular complexity of these malignancies. To achieve this, our research is organized into three themes:
- Metabolic liver disease(s)
- Immunogenomics
- Epigenomics remodeling
Research areas with project opportunities
Metabolic shifts in the serum landscape are particularly of interest in biomarker development since metabolic disorders often go clinically unmanaged, allowing the disorders to develop and progress into e.g., cancer. With participation in LEAD, we aim to strengthen our research into metabolic liver diseases.
As an example: In 90% of liver patients, cancer (i.e., HCC) develops on a background of chronic liver disease that is associated with a rapid rise in non-viral, steatotic liver disease (SLD). Forecasts predict that metabolic dysfunction associated steatotic liver disease and increased alcohol-related cirrhosis alone will affect the global population by more than 25% in 2030 and contribute to 40% of HCCs.
This increasing prevalence of metabolic liver syndromes poses a severe clinical challenge and socio-economic burden. HCC surveillance of cirrhotic patients with ultrasonography examination every 6 months is important but presents a sensitivity for early-stage HCC as low as 28%. Therefore, HCC patients are often undiagnosed until late stages when they are ineligible for treatments with curative intent such as tumor resection or liver transplantation. To alleviate this urgent problem, the development of 1) diagnostic biomarkers to identify HCC early, are essential. Furthermore, we need 2) prognostic biomarkers to determine the risk of tumor development and to develop novel therapeutic strategies. Finally, we currently have limited understanding of the mechanistic regulation either in the processing of metabolites or by the metabolites, themselves.
To lift these projects, we seek postdocs who have specialized knowledge and interests in 1) liver metabolism, 2) metabolic regulation, and 3) informatics.
Examples of recent papers:
- The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma.
- Serum IL-6 as a prognostic biomarker and IL-6R as a therapeutic target in biliary tract cancers
- Serum lipidome unravels a diagnostic potential in bile acid diarrhoea.
- Whole blood microRNAs capture systemic reprogramming and have diagnostic potential in patients with biliary tract cancer.
For further information about Andersen group
Overall research theme(s) –It may take years for a tumor to become invasive. We are investigating non-mutational mechanisms of pancreatic cancer initiation and tumor evolution.
Research areas with project opportunities
Tissue injury increases the risk of pancreatic ductal adenocarcinoma through not well-defined mechanisms. Common to the regenerative program of multiple tissues, pancreatic injury triggers inflammation and the emergence of transient cellular states with regenerative capacity. This process, defined as cellular plasticity, is crucial to regeneration; however, it represents a vulnerability in which environmental and genetic factors conspire to induce cancer. My laboratory studies cellular plasticity in pancreas regeneration and cancer with a focus on applied research and human health. At BRIC, we have identified developmental factors that regulate acinar plasticity and cancer initiation. The long-term goal is to devise cancer therapies based on altering acinar plasticity in regeneration and cancer. To achieve this goal, we combine cell and molecular biology with quantitative imaging and computational analysis of sequencing datasets in time-resolved experiments using acinar explants, organoids, and mouse genetics.
Overall research theme(s)
Our lab’s research sits at the intersection of molecular biology, developmental biology and systems biology and it combines experimental approaches and “big” biological data analysis.
Research areas with project opportunities
The lab is integrating cutting-edge single-cell research with novel computational analysis with the aim to address unresolved questions in developmental and cancer biology. In particular, we are interested in utilising single-cell RNA-sequencing (scRNA-seq), scATAC-Seq and spatial transcriptomics (STx) to:
- map in detail how transcriptomic states change in spatial cell-to-cell interactions of immune and tumour cells, and between cytolytic and regulatory immune cell types.
- understand transcriptional and epigenetic changes that occur in blood stem cells during development.
We are particularly looking to establish CRISPR screening approaches in the lab but also to further develop computational tools relevant for the multiomics data analysis.
Name of research group: Neuroinflammation Unit
Name of Principal Investigator: Shohreh Issazadeh-Navikas
Overall research themes
Understanding the molecular mechanisms of neuroinflammatory, and neurodegenerative diseases by utilizing bioinformatic tools to analyze big data sets.
Research areas with project opportunities
Our team focuses on neuronal immunity, the interaction between the immune and central nervous systems—specifically, the cross-regulation between immune genes and neurons in the CNS.
Currently our lab puts emphasis on understanding how these immuneregulatory genes controlling neuronal maintenance via controlling mitochondrial homeostasis, metabolism and mitochondrial DNA integrity utilizing large omics data generation and bioinformatic analysis.
Research areas with project opportunities
- Mitochondrial biogenesis in neuroimmune and neurodegenerative diseases
- Omics and bioinformatics
Overall research theme(s)
We use cutting-edge super-resolution microscopy approaches and multi-omics to investigate how dysregulation of 3D chromatin organization leads to disease, including cancer.
Research areas with project opportunities
Mutations caused by DNA damage enable a normal cell to become cancerous. Cells have therefore evolved a complex network of biochemical pathways to recognise and repair damaged DNA, collectively termed the DNA Damage Response, which acts as an anti-cancer barrier.
We recently discovered a new link between the DNA Damage Response and 3D chromatin organisation. Accordingly, individuals with inherited mutations in many DNA repair and chromatin architecture genes are predisposed to cancer.
In order to exploit the relationship between these processes and develop new clinical strategies, it is critical to molecularly resolve the role of 3D chromatin organisation during DNA repair and its dysregulation in cancer.
Our research programs include development of super-resolution imaging technology and AI-driven biomedical data analysis, molecular characterization of tumor suppressor genes, and identification of clinically relevant strategies that exploit the interconnection of 3D chromatin organization and DNA repair. Our current areas of focus are the function of 3D chromatin organiser proteins in DNA repair, the consequences of DNA breakage to 3D chromatin topology, and the role of 3D chromatin organisation in the development of breast cancer.
Our group is a new research team at BRIC with an energetic, creative and multi-disciplinary culture. The successful candidate will be part of an international, highly collaborative team with plenty of opportunities for interactions with the team, BRIC and international collaborators. For this position, we seek an enthusiastic, driven and collegial individual with a broad background in tissue culture, gene editing and molecular biology.
Overall research theme(s)
Our group focuses on biochemical and biophysical characterization of disease-relevant proteins and their ligands—our current emphasis is on intravascular lipolysis. We provide a detailed understanding of how a given pathway maintains homeostasis in normal physiology and why certain genetic aberrations cause dysregulation resulting in pathophysiology.
Research areas with project opportunities
We are using cutting-edge biophysical methods to characterize the interaction and dynamics of proteins involved in the regulation of intravascular lipolysis. Recently, we showed how intrinsic protein disorder and protein metastability are key factors in the regulation of lipoprotein lipase (LPL) activity and its cellular compartmentalization. This work led to the unexpected discovery that activators increase lipase activity by stabilizing LPL while inhibitors decrease lipase activity by catalyzing the unfolding of LPL via protein destabilization. To obtain this knowledge, we apply biophysical methods (e.g. SPR, CD, nano-DSF, SAXS, HDX-MS, MST, DLS) to characterize our purified recombinant proteins produced in house.
In the future studies, we would like to implement cryo-EM studies and we would like to extend our studies to other lipases, in particular endothelial lipase.
Overall research theme(s)
My lab is interested in exploring the importance of stem cell heterogeneity in normal and malignant hematopoiesis. Specifically, we seek to model pre-malignant conditions with the aim to identify actionable targets for the prevention of hematological malignancies.
Research areas with project opportunities
Hematological malignancies develop over decades and while the actual malignancy is associated with poor treatment outcome, the long latency of the pre-malignant phase may constitute a window of opportunity for targeting aberrant clones before the manifestation of full-blown disease.
To this end we have started to model human pre-malignant conditions such as clonal hematopoeisis (CHIP) and clonal cytopenia of indeterminate potential (CCUS) in xenograft models using CRISPR technologies in human hematopoietic stem cells, with the ambition to develop experimental tractable systems for assessing disease biology and target identification in a human context. Technology-wise we use a range of omics and single-cell technologies to characterize pre-maligant and malignant conditions including our recently developed single cell proteomics (scMS) workflow that allows us to quantify >1.000 proteins in individual cells. We will explore these technologies to seek to identify how early lesions evolve and to identify potential points of therapeutic intervention. To that end we will further develop of scMS workflow to allow for targeted scMS of (but not restricted to) transcription factors and cell surface proteins. We will also work on further developing our computational workflows which will also include work on integrating scMS with other modalities such as scRNA-seq and scATAC-ses.
Overall research theme(s)
- Specialized translation in development and disease
- Ribosomal RNA modifications
- Cancer and neurobiology models
Research areas with project opportunities
The ribosomal RNA (rRNA) is heavily decorated with a wide array of post-transcriptional modifications, the most abundant of which is 2’-O-methylation (2’-Ome). We have mapped the presence of 2’-Ome sites on the rRNA from a large panel of cell lines, tissues, and tumor samples, and find that some 2’-O-me sites are methylated only on a subset of ribosomes.
Furthermore, some sites are dynamically methylated in normal physiological settings, such as brain development and cellular differentiation, following activation of oncogenic signaling, and during tumorigenic processes. Hence, our data indicate the existence of multiple ribosome subtypes, some of which may have specialized functions. Based on this, we explore the hypothesis that differential 2’-Ome alters the properties of ribosomes and imposes selective translation. Extending from this, we study if differential 2’-Ome constitutes a “coding” of the ribosomes to instigate specific translational programs. Such programs may be crucial during normal development and cellular homeostasis as well as under disease conditions. We also work to identify compounds that selectively inhibit ribosome subtypes found in disease.
Key methods include cell and organoid models, CRISPR-based genome editing, Ribometh-seq, RNA-seq, Ribosome profiling, mass spectrometry, and translation assays.
Some of our recent papers:
- Ribosomal RNA 2’-O-methylation dynamics impact cell fate decisions.
- Ribosomal RNA methylation induced by MYC impacts translation to promote cell proliferation.
- Translational control through ribosome heterogeneity and functional specialization.
All projects in the group are centered around the theme of specialized translation and we value collaboration and collegiality.
Overall research theme(s)
We are a computational biology laboratory working at the intersection of genomics, transcriptomics, epigenomics, gene editing and machine learning. We apply ourselves to understanding biological mechanisms operative in cancer genome evolution, human population genomics and in metagenomes.
Research areas with project opportunities
We are interested in using statistical genomics analysis to understand biological quality-control (QC) mechanisms operating in human cells. We want to understand QC mechanisms at three levels: DNA level (genomic instability, mutagenesis, DNA repair), mRNA level (NMD, splicing, allele specific expression), and gene function level (epistasis, synthetic lethality). We are particularly interested in questions that bridge these 3 levels, for instance “what are the consequences of DNA repair deficiencies on transcriptomes via increased mutation burden, and how this generates opportunities for tumor immunotherapy?”. We are also interested in application of the gained knowledge to diagnosis, therapy, and prevention of cancer and of heritable genetic diseases. The tools we apply are a variety of bioinformatics, statistical and machine learning methods to analyze human genomes, transcriptomes, and epigenomes, often derived from tumors; we also analyze population genomic data and metagenomes. We have a keen interest in applying modern artificial intelligence methods to DNA and mRNA sequences. We are interested in using long-read sequencing of DNA and mRNA by Nanopore to better characterize tumor evolution. We further perform experimental work using combinatorial gene editing techniques (Cas12a) in cell lines to model disruption of disease genes and the downstream effects on mutation rates, transcriptome stability and genetic interactions.