DanStem (2011 - 2022) - Nordisk Foundation Centre for Stem Cell Biology
DanStem was an international research centre working for basic stem cell and developmental biology. The aim was to address fundamental questions in stem cell and developmental biology with an overall aim to contribute to the development of new therapies for cancer and chronic diseases such as diabetes.
Parts of the research have continued at the Centre for Stem Cell Medicine, reNEW at University of Copenhagen.
The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) was instituted in 2011 as an international research centre for basic stem cell and developmental biology with a grant from Novo Nordisk Foundation. Danstem was active from 2011-2022. The centre was part for the Faculty of Health and Medical Sciences at University of Copenhagen.
The initial overarching goal to raise the profile of stem cell research and technology and make Denmark a leading country in the pursuit of stem cell-based diabetes and cancer therapies. They worked to create a strong platform for utilizing pluripotent, somatic and cancer stem cells in synergistic efforts to understand development, homeostasis, and disease in endocrine organs such as the pancreas, as well as cancer. This resulted in a series of international group leader recruitments coupled with local, internationally recognized research groups.
The researchers at the centre focused on solving complex problems in stem cell and developmental biology, spanning early embryonic development and organogenesis through advanced disease development and cell or drug-based therapies.
Recent years research
In more recent years, the Centre evolved to address fundamental questions more broadly in stem cell and developmental biology with an overall aim to contribute to the development of new therapies for cancer and chronic diseases such as diabetes, currently hosting two major, strategic translational research programs in diabetes and haematological cancers.
The centre was built and headed by Professor Henrik Semb.
DanStem Research Areas
Uncovering the mechanisms and coordination of stem / progenitor cell self-renewal and differentiation is essential to gaining a fundamental understanding of tissue and organ development and their potential use in regenerative medicine. Therefore, DanStem research aims was to solve complex problems in stem cell and developmental biology spanning early embryonic development and organogenesis through advanced disease development and cell and drug-based therapies.
Through an increasingly quantitative approach with advanced imaging and single cell analyses, the DanStem researchers were teasing out the details of how specific cues transduce to gene regulatory events, such as modulation of epigenetic states or gene transcription, to control stem cell behaviour. These studies allowed DanStem to unravel fundamental issues in the field and facilitate the translation of novel insights into medical practice especially in the areas of diabetes and haematological cancers.
Cells of Knowledge
Below, is a short introduction to stem cell research. The video is a result of collaborative effort of animators from the Animation Workshop in VIA University College and scientists from DanStem,
Titles and information found here reflect the positions and information about the members at the time of working at DanStem.
The gut is a key organ in coupling systemic signals or environmental cues with organism growth, metabolism, immune activity, longevity or behavior. Understanding the robust strategies involving intra- and inter-organ signaling pathways that evolved to preserve gut size in homeostatic conditions and growth during damage-induced regenerative phases has a high impact in the field of regeneration, inflammation diseases and cancer biology.
The Aragona group aimed to understand how neighbouring cells coordinate their decisions to build tissues with specialized structure and function. In particular, they want to investigate how tissue architecture is maintained and how mechanical cues affect gene transcription, stem cells dynamics and fate decisions.
The Arnes group investigated how molecular determinants of cellular identity, with a particular focus in non-coding RNAs, regulate the initiation and progression of pancreatic cancer.
The Brickman group aims to understand the transcriptional basis for early embryonic lineage specification. In particular the group is interested in dynamic mechanisms by which cells can both reversible prime towards a particular fate or undergo a transition into commitment.
The Ferretti group aims to identify and characterize the molecular mechanisms establishing the mesodermal diversity at the time of gastrulation with the purpose of meliorating the existing protocols of mesoderm differentiation. The group long-term goal was to generate robust models for mesoderm differentiation that will help in conceiving innovative protocols for hESCs mesoderm differentiation.
The Grapin-Botton group investigates the impact of the cellular and organ architecture on the cells’ fate choices and how single cells act in a community to generate an organ.
The overall vision of the group is to understand the pathogenesis of cancers of the hematopoietic stem cells and improve the survival of patients with these disorders through the integration of basic and clinical research.
The Helin group aims to understand mechanisms regulating transcription, cell identity and cancer towards the development of novel therapies for cancer treatment.
The epithelial of the skin and intestine epithelia rely on stem cells for their constant and life-long replenishment. It remains unknown when and how these stem cell first appears during development, how stem cell behaviour is regulated during steady state homeostasis, and to what extent these regulatory mechanisms are altered during regeneration and disease. Insight into these questions will be pivotal for a mechanistic understanding of tissue maintenance, establish cell sources for regenerative therapies and identify new therapeutic targets. The main objective of the Jensen group is using state-of-the-art quantitative approaches to address these outstanding questions.
The Kirkeby group studies the factors involved in human neural subtype specification to enable production of specific neurons for understanding and treating neurological diseases.
The Ober group aims to understand how a functional organ is built from a population of self-organising progenitor cells. In particular, which morphodynamic processes control initial progenitor migration and subsequently their differentiation into epithelial unites organized into a functional architecture.
The aim of research in the group is to dissect stem cell hierarchies in the normal human breast and in breast cancer, with a view to finding the cell of origin in different breast cancer subtypes.
The Porse group studies the gene regulatory processes governing the behavior of hematopoietic stem cells in normal hematopoiesis and leukemic stem cells in acute myeloid leukemia.
The Sedzinski group aims to understand the general principles underlying epithelial homeostasis. Particularly, they want to determine both the mechanics and molecular regulation of epithelial cell renewal from stem cells hoping to provide new insights into treatment of epithelial pathologies associated with defective tissue homeostasis, such as asthma, colitis, and most common epithelial tumours, or carcinomas.
The Semb group has two main goals:
- to understand the connection between epithelial architecture and the commitment of pancreatic progenitor cells to mature endocrine cells and vice versa.
- to translate this knowledge into efficient and reliable strategies for regenerative medicine in diabetes. These objectives are applied, primarily, to their organ of choice – the pancreas.
The Serup group investigates how cell-cell signaling interfaces with lineage-specific transcription factors to regulate cell fate decisions. The group main focus is on how Notch signaling controls progenitor behaviour and differentiation in the developing pancreas. They explore the generality of their findings in other organ systems. They uncover novel principles in the gene regulatory network architecture and how ultradian oscillations in gene activity are linked to cell fate choice.
Lead by Associate Professor Kim Therilggard-Mönch.
Our research group conducts a patient-centric translational preclinical program aiming at the identification and validation of novel therapeutic strategies eradicating LEUKEMIC STEM CELLS in patients with ACUTE MYELOID LEUKEMIA. In addition, we apply our newly identified human hematopoietic stem cell (HSC) marker to refine the human HSC immunophenotype and explore its clinical potential for production of highly purified stem cell grafts applicable for autologous stem cell transplantation of AML and other cancer patients, as well as gene therapy of patients with monogenic diseases
Lead by group leader Joachim Lütken Weischenfeldt.
We are interested in the mutational mechanisms and clonal evolution of cancer, in particular mechanisms of complex structural variants and the impact on 3D chromatin organization.
Lead by Professor Krister Wennerberg.
We are interested in discovering precision cancer therapies targeting the cancer cells that survive current therapies and eventually cause the cancer to grow back, such as cancer stem cells. To accomplish this, we explore functional studies of cancer cell cultures and how different subpopulations respond to different treatments.
Lead by Associate Professor Kyoung Jae Won.
The goal of the laboratory is to develop computational tools to unravel biological mechanisms and enhance our understanding of biological systems integrative data analysis.
The Żylicz group wants to understand how metabolic and epigenetic mechanisms cooperate to regulate transcription during early development. In particular we are interested in how metabolism regulates histone modifiers, and how these in turn affect lineage choice and embryo growth at around the time of implantation.
Translational Stem Cell Research and Therapy at DanStem was focused on the translation of promising basic research results into new strategies and targets for the development of new therapies for hematological cancer and diabetes. The aim was to strengthen these fields towards clinical application.
- Development of a safe and efficient therapy for diabetes based on human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), including development of scalable differentiation protocols for functional insulin-producing beta cells.
- Establishment of human iPSC-based in vitro models for inherited forms of diabetes.
- Identification and validation of novel targets for anti-cancer therapy.
- Strengthening both the short- and long-term research and clinical management of blood cancer.
Program for Translational Hematology PTH
The vision of PTHw was to improve the survival of patients with blood cancers by optimizing the use of already approved drugs, identify new targets for therapy, develop novel therapies, test potential novel drugs in pre-clinical models, and collaborate with pharmaceutical companies on developing new drugs and test these and other novel drugs in Phase I-II clinical trials. The overall goals was to have an immediate impact on how patients are treated today, improve the understanding of genetic, epigenetic and molecular mechanisms leading to blood cancers, suggest new validated targets for the development of anti-cancer therapy, to strengthen both the short- and long-term research and clinical management of blood cancer, and to improve the overall outcome of treatment for blood cancer patients.
Focused on delineating gene regulatory networks in normal and malignant stem cells in order to understand how normal hematopoietic stem cells are distinct from their leukemic counterparts and to identify novel candidates for future drug development.
Aimed to understand and target the progression from clonal cytopenia of undetermined significance (CCUS) to myelodysplastic syndrome (MDS) as well as the molecular aberrations underlying mantle cell lymphoma (MCL).
Investigates the mechanisms that regulate cell-fate decisions in stem cells, differentiated cells as well as tumor cells with the aim of gaining new insights into the molecular mechanisms leading to cancer.
Major focus was to characterize and target cancer stem cells (CSCs), as well a to improve prognostification in patients with Acute Myeloid Leukemia (AML).
Aimed to further our understanding of the genome by integrating large-scale genomic datasets and develop computational methods to exploit multi-dimensional genomic/epigenomic landscapes to understand cell-type specific or spatio-temporal gene regulation.
Was interested in the mutational mechanisms and clonal evolution of cancer, in particular mechanisms of complex structural variants and the impact on 3D chromatin organization.
Program for Translational Diabetes Research
The overall goal of the Program for Translational Diabetes Research was to establish a safe, scalable and cost-effective stem cell therapy for T1D patients. This goal signifies a key step in the long-term objective to develop an academic program that, in collaboration with leading basic and clinical researchers, regulatory and ethical consultants, and cell manufacturing, hospital and industrial partners, aims to provide a stem cell-based therapy for a large number of T1D patients.
Had the goal to develop large-scale manufacturing protocols of for stem-cell derived allogenicmature beta cells for future clinical needs.
Pancryos (DanStem spinout project)
Aims to develop a next generation stem cell derived allogenic cell therapy (PanINSULA™) for type 1 diabetes, based on novel IP in the differentiation of stem cells into mature beta cells and in the purification of pancreatic progenitor cells. PanCryos has assembled a team with experts in stem cell biology, islet transplantations, business, and regulatory guidance.
Co-founder and CEO: Dr. Jacqueline Ameri
Co-founder and Advisor: Professor Henrik Semb