Host research groups

Principal Investigator: Jesper B Andersen.
Webpage of Andersen group

Overall research theme(s)

We focus on clinical solutions in hepatobiliary cancers to unravel perturbed mechanisms required for these tumors to develop, to grow and to metastasize. Our research programs include integrative omics-driven patient characterization and stratification, biomarker discovery, epigenetic therapy, and metabolic diseases.

Existing or interest to establish new collaborations with clinics:

We have extensive collaborations worldwide, but always welcome new members in the network. Dr. Andersen is co-founder of the European Network for the Study of Cholangiocarcinoma – ENSCCA (http://www.enscca.org/).

Existing or interest to establish new intersectoral connections: We are always interested in extending our biological understanding of the liver and hepatobiliary system, learning and/or collaborating on new research areas helping us alleviate clinic problems. We recently started implementing artificial intelligence (AI) to guide multiple data integration, image analysis as well as spatial single cell digital pathology.  

Dimension of diversity in the team and inclusive environment for hosting a medical doctor: Our research group is multidisciplinary, hosting both a wet-lab and bioinformatic sections. The group is multi-lingual, -ethnic and gender-diverse. Existing or interest to establish new collaborations with clinics (co-supervisor from clinic)

• Research area(s) with project opportunities 
• What? Immunogenomics: steps towards personalized medicine in bile duct cancers.
• How? Omics-driven methodologies (single cell transcriptomics and proteomics); multiple immunohistochemistry staining (MACSima); molecular and cell biology and informatics
• Why? Bile duct cancer patients are often diagnosed with locally advanced or metastatic disease, and most patients survive less than 1 year. The pathogenesis of these malignancies is characterized by chronic inflammation and extensive desmoplasia, contributing to aggressive disease behavior and poor response to for example, checkpoint inhibitors. Local and systemic inflammation is intensified by chemotherapy, with both pro- and anti-tumor effects. In this project, we will investigate the disease causality.

Principal Investigator: Ana Cvejic

Webpage of Cvejic group

We are focusing on the dissection of the heterogeneity of cellular states in the blood system using single-cell approaches (scRNA-Seq, scATAC-Seq, spatial transcriptomics). We are working with human foetal haematopoietic cells as well as cancer patient samples.

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 understand transcriptional and epigenetic changes that occur in blood stem cells during development. The lab is accepting applications from applicants with background in computational biology that will implement existing and develop novel approaches for data analysis. Understanding the mechanisms that maintain the foetal haematopoietic programme will ultimately provide means to enhance numbers and potency of blood stem cells through ex-vivo manipulations for their greater use in regenerative medicine. We anticipate that the results from this study will provide unprecedented insight into the blood formation during human development.

Principal Investigator: Shohreh Issazadeh-Navikas.
Webpage of Issazadeh-Navikas group

Overall research theme(s):
Neuroimmunology of neurodegenerative diseases and ageing.

Existing or interest to establish new collaborations with clinics (co-supervisor from clinic):
We have long-lasting established collaborative work with MS clinics and PD clinical groups and geneticists

Research area(s) with project opportunities:
We are focused on identifying novel immune genes and their functions in central nervous system, dysfunction of which could cause mitochondrial dysfunctions and thereby neuronal cell death. We are dedicated to utilize in vitro, and in vivo models as well as patients’ material to reach novel findings with translational value. As neurodegenerative ageing diseases are among highly raising diseases of mankind, because of the ageing population, there are tremendous unmet needs to understand the basic molecular mechanisms operating in these diseases, with aim to find cure and/or effective therapies.

Principal Investigator: Bjarne Winther Kristensen
Webapage of Kristensen group

Name of research group: Kristensen Group

Description of the research group: Our scientific goal is to obtain a deeper understanding of brain cancer and thereby to discover novel promising therapeutic approaches for glioblastoma patients. We have a strong focus on the microenvironment using novel single cell and spatial approaches. Our lab comprises 3 postdocs, 4 PhD students 3 MSc students and two technicians. We are at the cutting edge in the microenvironment field having the newest equipment. With our translational university-hospital profile and group members with both MD and MSc background, we use patient tissue for discovery and validation having the main goal to get back to the patients with therapeutic progress. In our research we have demonstrated that the microenvironment is critical for aggressiveness and recurrence of glioblastoma. We have also found that microglia-macrophages protect against chemotherapy and shorten patient survival and that genetic alterations influence microenvironment. Illustration our leading position, we hosted and organized the last European Congress of Neuropathology.

Glioblastoma is the most frequent and malignant brain tumor with 15.000 new cases per year in the EU. Standard of care includes surgery followed by radiation and temozolomide (TMZ) chemotherapy. Glioblastomas are characterized by extensive areas with hypoxia, peri-necrotic tumor cell palisades and microvascular proliferation, which are diagnostic hallmarks of glioblastoma. These aspects are part of the hypoxic niche in glioblastoma and has been associated with stem-like tumor cells and therepeutic resistance. In surgically removed glioblastoma tissue, a special type of immune cells called tumor-associated microglia and macrophages have been reported to constitute up to 30 % of the cells, a fraction that is even higher in hypoxic areas. These cells are capable of secreting cytokines, chemokines and growth factors, thereby influencing the microenvironment. However, their influence on tumor cell phenotype and therapy resistance - in a hypoxic microenvironment - has only been sparsely studied and is not understood. The overall aim of this project area is to interrogate the microglial/macrophage and tumor cell phenotype in the hypoxic niche to understand this critical area more deeply and identify novel therapeutic targets. 

We use “spatial profiling” to obtain both gene regulation data for cell clusters (up to 18.000 genes) and individual cells (up to 1000 genes) knowing at the same time exactly where the glioblastoma tumor cells and their neighbor cells are localized. We plan to validate presence of target candidates involved in critical cross-talk at the protein level by immunofluorescence multiplexing followed by functional investigation of the role of target candidates using patient tumor cell cultures established in our laboratory. To investigate the most promising targets, we use orthotopic pre-clinical models for primary and recurrent glioblastoma.

Novel therapeutic strategies taking into account that tumor cells are in fact intermingled with high numbers of macroglia/macrophages that influence the tumor cells may be key to therapeutic progress within the next decade. The last decades, the major focus has primarily been on tumor cells alone. With the strategy in this project, we expect to identify novel, clinically relevant targets by taking the interactions between tumor cells, microglial/macrophage and microenvironment into account.

Name of Principal Investigator: Anders H. Lund

Webpage of Lund group 

Overall research themes:

• Translation programs via ribosome specialization
• Molecular disease mechanisms with focus on cancer

Existing or interest to establish new collaborations with clinics: Existing links to clinical groups working on hematological and colorectal cancer. Currently no clinical supervisors

What: A mammalian cell holds millions of ribosomes which are not identical translation machines but have distinct compositions and modifications, creating heterogeneous ribosome populations. Published and preliminary data sustain the hypothesis that specialized ribosomes conduct specific translational programs of key importance in the faithful execution of gene expression programs underlying normal development and pathologies. Importantly, cancer cells contain a different repertoire of specialized ribosomes likely supporting translational programs required for the cancer to establish and develop. We work to identify compounds that can selectively inhibit ribosomes enriched for in cancer cells.

How: We profile cell and tissue samples from cellular model systems as well as patient samples to identify ribosome subtypes. The subtypes are subsequently modelled using for instance CRISPR technologies and assayed for their translational capacities in cells and in vitro assays using transcriptomics and proteomics approaches. In addition, we conduct compound screens to identify potential new drugs that selectively inhibit cancer-associated ribosomes.

 Why: Cancer cells are characterized by unlimited growth which in many cases requires deregulation of the protein synthesis machinery. The vision is to understand how cancer hijacks the translation machinery and to develop compounds to selectively block translation in cancer cells.

Principal Investigator: Fena Ochs
Webpage of Ochs group

Overall research theme(s)

We use cutting-edge super-resolution microscopy approaches and multi-omics to unravel how dysregulation of 3D chromatin organization leads to development and progression of cancer. Our research projects include development of super-resolution imaging technology and AI-driven big data analysis, molecular characterization of tumor suppressor genes and identification of clinically relevant inhibitors by exploiting the relationship of 3D chromatin organization and DNA repair. 

Dimension of diversity in the team:

We are a new research group at BRIC and will establish an energetic, creative and multi-disciplinary environment. Our aim is to build a collegial, inclusive and diverse workplace to do rigorous and reproducible science that advances our understanding and treatment of disease.

Research area(s) with project opportunities

What: 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 novel anti-cancer treatment strategies, it is therefore critical to molecularly resolve the role of 3D chromatin regulation during DNA repair and its dysregulation in cancer.

How: The successful candidate will employ multiplexed gene editing and cutting-edge live super-resolution microscopy to decipher the role of CTCF and cohesin in DNA repair and tumour suppression. They will integrate biomedical imaging data with multi-omics to investigate how these proteins control genome stability and chromatin organisation in single cells and patient tumour cell cultures established in our laboratory.

Why: This work will yield fundamental insight into the role of chromatin architecture proteins in the development and progression of a wide-range of cancers including myeloid leukaemia and glioblastoma. Our vision is to molecularly characterise the relationship between 3D chromatin organisation and genome stability and to exploit this relationship for the development of novel therapeutic strategies.

Name of Principal Investigator: Bo Porse.
Webpage of Porse group

Overall research theme(s):

Delineation of gene regulatory networks governing normal and malignant hematopoiesis.

Existing or interest to establish new collaborations with clinics (co-supervisor from clinic):

We have an established/long-term collaboration with Professor in Hematology Kirsten Grønbæk (Rigshospitalet, University of Copenhagen, Denmark).

Research area(s) with project opportunities:

Research avenues:
The Porse group is specifically interested in the processes governing stem cell function and differentiation processes within the hematological system. Our projects evolve around characterization of the regulatory machinery and consequences of genetic and epigenetic changes in hematopoietic cells.  

Lastly we are very focused on investigating the mechanisms involved in disease development, specifically in acute myeloid leukemia, using in vitro and in vivo models. In projects with more translational focus we use patient samples and analyze these with the overall aim of identifying new targets to improve the treatment outcome for these patients. 

We are a part of Program for Translational Hematology and therefore have access to a large and unique biobank with samples from Danish hematological patients. We use these samples to study the genomic, epigenomic and proteomic landscape in different stages of disease development as well as the and functional consequences of the disease causing alterations these cells possess.

State-of-the-art technologies are used to answer our research questions and we benefit from both long-term internal experience, as well as from tight collaborations with other groups and core facilities at BRIC and the Hospital departments. :

Flow cytometry analyses and sorting, Genetic screens (in vitro and in vivo), and murine models (GEMMS). We also use Patient derived Xenograft models (PDX) and sequencing methods (eg. DNA, RNA, histone- and DNA-modifications, HiC and CITE-seq) bulk and single cells approaches. Finally, we are applying our newly established single cell mass spectrometry platform to investigate the proteome on a single cell level in both human and murine cells.

Principal Investigator: Joachim Weischenfeldt.
Webpage of Weischenfeldt group

Overall research theme(s):
we use integrative computational approaches to study the clonal evolution and mutational processes that give rise to aggressive, treatment-resistant cancer.

Existing or interest to establish new collaborations with clinics (co-supervisor from clinic):
We are closely collaborating with clinical colleagues across a wide range of areas related to cancer genetics and genomics.

Research area(s) with project opportunities:

What: Why certain individuals acquire cancer is poorly understood for the majority of patients, but differences in our germline genome is known to play an important role and specific inherited mutations can cause complex mutational patterns. We are particular interested in the larger structural variants in cancer genomes, which are associated with defects in various processes including DNA repair and replication. The project will involve development and application of e.g. single cell sequencing and long-read methodologies to identify how mutations in the germline and tumor can cause complex mutational processes and cancer.

How: Possibility to perform both wet-lab based analysis as well as data-driven, bioinformatics analysis of mutational patterns. You will be working with patient-derived tumor material and apply latest sequencing-based analyses to explore the mutational processes leading to the disease. You will be part of a team of national and international researchers, with plenty of possibilities for interactions and development of own research ideas.

Why: Cancer is a disease of the genome. We aim to identify the mutational processes that drive progression.

Name of Principal Investigator: Krister Wennerberg 
Webpage of Wennerberg group 

Name of research group: Wennerberg group

Overall research themes of the research group (short Overview Max 3 lines)

Our goal is to understand mechanisms of drug sensitivity and resistance in individual cancers, and in particular the subsets of cells that persist treatment and drive cancer recurrence. Through this knowledge, we aim to identify new effective cancer precision medicine strategies.

Research area(s) with project opportunities (please address the three topics below; max half page in total)

The pro-apoptotic BCL-2 inhibitor venetoclax is changing the treatment of elderly and unfit patients suffering from acute myeloid leukemia (AML). When combined with azacitidine, a standard-of-care hypomethylating agent, venetoclax induces remissions in the majority of elderly/unfit AML patients and overall survival is significantly extended. However, most, if not all, cases will eventually relapse and there are currently no viable and effective approaches to treat venetoclax-azacitidine-relapsed patients. We therefore need to understand and be able to predict the mechanisms of resistance for this therapy better and identify clinically relevant ways to avoid or overcome resistance development.

 You will be using a unique set of samples from two clinical trials where AML patients have been treated with venetoclax-azacitidine. We have patient samples both from responding and non-responding cases as well as paired sets of samples at diagnosis (treatment sensitive) and at relapse (treatment resistant) and are all clinically annotated and molecularly profiled. Using state-of-the-art experimental methodologies, you will explore these patient samples to gain new profound understanding of the molecular, phenotypic and genetic mechanisms behind resistance to the venetoclax-azacitidine in AML and most importantly, how resistance could be overcome or prevented. Working with clinical hematologists across the Nordic countries, the goal is that your discoveries will be converted into clinical trials where we explore new therapies overcoming venetoclax-azacitidine resistance in AML patients.

As the venetoclax-azacitidine treatment is becoming the standard therapy for elderly and unfit AML patients, the next clinical frontier will be how to tackle the treatment resistance that will emerge in most cases. You will be addressing this challenge in collaboration with a multidisciplinary team of experimental and clinical scientists.