SFO grant awardees 2018
The SFO for Stem Cells and Regenerative Medicine is proud to announce six awardees in the 2018 application round, two in each category.
The SFO for Stem Cells and Regenerative Medicine is proud to announce six awardees in the 2018 application round, two in each category. All applications were reviewed by an international team of five prominent researchers within the field. The awardees will present a research summary at the website within 2 weeks. They will also present their research programmes at the upcoming Karolinska Institutet SFO StratRegen Conference 18-19 October 2018. Please find the list of awardees and the link to the conference registration website.
The SFO Steering Group is concerned about the fact that no women were granted this year and discussed it in detail. The international review board (3 men and 2 women) has no conflict of interest with any of the applicants or the Steering Group. They reviewed applications without direct information about gender, which in several cases was not obvious from the name. The fact that the difference between the granted applicant with the lowest score and the non-granted female applicant with the highest score was equal or more than 3, made us decide according to the recommendation of the review board.
However, the issue how to support applications from female researchers is crucial for a successful university and will be discussed at the upcoming SFO conference 18-19 October.
Senior grant awardees
Ernest Arenas - A reprogramming strategy to treat Parkinson’s disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of midbrain dopaminergic neurons (mDAs). The treatment of PD is currently symptomatic and there is no cure. Clinical studies using human midbrain fetal tissue for transplantation have provided proof of concept that cell replacement therapy can change the course of PD. Current cell replacement strategies include the transplantation of human stem cell-derived midbrain progenitors or the direct reprogramming of endogenous striatal astrocytes into induced dopaminergic neurons (iDANs), a strategy that we recently developed (Rivetti et al., 2017, Nature Biotechnology). The cause of PD is largely unknown and in only few of the cases a genetic cause has been identified. It is currently thought that most PD cases arise from the interaction between multiple genetic and environmental risk factors. We recently found that PBX1, a transcription factor (TF) required for the specification and maintenance of mDAs, is nearly absent from the nuclei of substantia nigra mDAs of PD patients in a selective manner (Villaescusa et al, 2016, EMBO). We hereby hypothesize that other neurodevelopmental TFs required to maintain the identity and function of mDAs may also be impaired. We thus propose to: (1) Identify neurodevelopmental TFs whose expression is altered in PD. (2) Examine the function of such TFs and determine their capacity to correct or prevent PD features in iPS cell-based in vitro models of PD. (3) Apply neuroprotective TFs in combination with reprograming TFs to develop a novel direct in vivo reprogramming strategy for PD by direct conversion of endogenous brain striatal astrocytes in situ into disease resistant iDANs. Our project will thus increase our understanding of the role of neurodevelopmental TFs in the physiopathology of PD and will develop novel therapeutic strategies for this disease.
Sten Eirik Jacobssen - Cellular, molecular and clinical surveillance of clonal hematopoiesis during aging
Aging is associated with perturbed tissue regeneration and increased risk for cancer. Recent studies identified recurrent oncogenic mutations in blood of healthy elderly individuals, carrying increased risk for development of hematological malignancies. We will investigate the cellular, functional and molecular impact of involved mutations and clonal hematopoiesis in mouse and man, through longitudinal studies of hematopoietic stem and progenitor cells in aged normal human individuals and mice, with the goal of establishing the cellular origin of mutations driving clonal hematopoiesis, and their impact on cell fate decisions in distinct stem and progenitor cells. These studies should provide a better mechanistic understanding of clonal hematopoiesis in elderly, how the involved mutations result in dysregulated hematopoiesis, and facilitate identification of novel therapeutic targets in preleukemic and leukemic stem cells.
Junior grant awardees
Olov Andersson - In vivo drug discovery for induction of β-cell neogenesis
Diabetes feature a reduction of functional β-cells, a key pathologic event that causes or exacerbates the dysregulation of glucose levels. To harness the pancreas’ regenerative capacity we must first unravel the mechanisms that underlie, and identify factors that drive, the regenerative expansion of the β-cell mass. In the project awarded by StratRegen, we will identify small molecules that can induce β-cell neogenesis from progenitors residing in the pancreatic duct using the zebrafish model. The zebrafish model is ideal for in vivo drug discovery, combining the high-throughput of in vitro screens with the physiological complexity and relevance of animal studies.
Andrei Chagin - A novel stem cell niche in the epiphyseal growth plate
Longitudinal bone growth is fueled by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for bones to grow. However, it remains unknown how this continuous supply is maintained throughout the entire period of growth. We found that longitudinal growth during the fetal/neonatal period involves depletion of chondro-progenitors, whereas later in life chondro-progenitors acquire the capacity for self-renewal. This change in cell behavior coincides with the formation of the secondary ossification center. Our findings indicate that a new stem cell niche develops postnatally in the epiphyseal growth plate, providing a continuous supply of chondrocytes over a prolonged period.
Clinical grant awardees
Niklas Björkström - Regeneration and hematopoiesis of the human liver
The liver is the only visceral organ that possesses remarkable capacity to. Although this process has been studied in model systems, how liver regeneration occurs in humans remains elusive. Our first aim is to define a role for the intrahepatic immune system in regulation of liver regeneration in a human clinical study. The liver contains large numbers of immune cells. We have recently reported on the existence of liver-resident immune cells in human liver. However, whether these liver-resident immune cells are self-maintained or recruited from the bone marrow is unclear. The second aim is to map the ontogeny of human intrahepatic lymphocytes. By addressing these aims, we anticipate generating novel understanding of regeneration and hematopoiesis in the human liver.
Andreas Björklund - Development of allogeneic Natural Killer Cell-Based Cancer Immunotherapy Against Myeloid Malignancies
Building on experiences gained from our recently completed clinical trial (Björklund et al. CCR, 2018) we will launch two investigator-initiated allogeneic natural killer (NK) cell-based cell therapy trials with the aim to make the therapy against AML and MDS more effective. In the first trial we will use short term IL-15 stimulated, metabolically optimized NK cells (MONK-cells) from haploidentical donors and in the second, so called adaptive NK cells (ADAPT-NK) will be selectively expanded from unrelated third-party donors with maximal alloreactivity against the recipient tumor cells. A successful treatment would be directly followed by an allogeneic stem cell transplantation to provide long-term cure.