Karin Forsberg‐Nilsson
A5060330917- Cancer, Hypoxia, and Metabolism
- Proteoglycans and glycosaminoglycans research
- Neurogenesis and neuroplasticity mechanisms
- Cancer Genomics and Diagnostics
- Extracellular vesicles in disease
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Virus-based gene therapy research
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Pluripotent Stem Cells Research
- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Fibroblast Growth Factor Research
- Lipid metabolism and biosynthesis
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Mesenchymal stem cell research
- Sarcoma Diagnosis and Treatment
- Veterinary Oncology Research
- MicroRNA in disease regulation
- Cellular Mechanics and Interactions
- Neuroblastoma Research and Treatments
Science for Life Laboratory
2016-2025
Uppsala University
2016-2025
University of Nottingham
2021-2025
Sunny BioDiscovery (United States)
2023
Ludwig Cancer Research
2007
Swedish Orphan Biovitrum (Sweden)
2003
National Institute of Neurological Disorders and Stroke
1996-1998
National Institutes of Health
1996-1998
Uppsala University Hospital
1998
The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for rabbit and compared it to resequencing data from populations wild domestic rabbits. identified more than 100 selective sweeps specific rabbits but only relatively small number fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) derived alleles. SNPs with marked allele frequency differences between were enriched conserved noncoding...
Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM essentially incurable its resistance to therapy attributed a subpopulation cells called glioma stem (GSCs). To meet present shortage relevant cell (GC) lines we developed library annotated validated derived from surgical samples patients, maintained under conditions preserve GSC characteristics. This collection, which call Human Cell Culture (HGCC) resource, consists biobank 48 GC an associated database...
Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes 240 species, we identify bases that, when mutated, are likely affect fitness and alter disease risk. At least 332 million (~10.7%) in human genome unusually conserved across species (evolutionarily constrained) relative neutrally evolving repeats, 4552 ultraconserved elements nearly perfectly conserved. Of 101 significantly constrained single bases, 80% outside protein-coding exons half...
Annotating coding genes and inferring orthologs are two classical challenges in genomics evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA (Tool to infer Orthologs from Genome Alignments), a method integrates structural gene annotation orthology inference. implements different paradigm orthologous loci, improves ortholog detection of conserved compared with state-of-the-art methods, handles even highly fragmented assemblies. scales...
The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis genetic variation across an alignment 241 mammal genome assemblies, addressing prior concerns regarding limited genomic sampling species. compared neutral genome-wide phylogenomic signals using concatenation coalescent-based approaches, interrogated chromosomes, analyzed extensive catalogs structural variants. Interordinal...
Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability discern which positions functionally important. Evolutionary constraint is a powerful predictor function, agnostic cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% the genome as significantly constrained and likely functional. We compared annotation, association studies, copy-number variation,...
We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. found that although mammals resemble one another total and diversity, they show substantial differences with regard recent accumulation. This includes multiple expansion quiescence events across mammalian tree. Young TEs, particularly long interspersed elements, drive increases size, whereas DNA transposons are associated smaller genomes....
Human accelerated regions (HARs) are conserved genomic loci that evolved at an rate in the human lineage and may underlie human-specific traits. We generated HARs chimpanzee with automated pipeline alignment of 241 mammalian genomes. Combining deep learning chromatin capture experiments neural progenitor cells, we discovered a significant enrichment topologically associating domains containing variants change three-dimensional (3D) genome organization. Differential gene expression between...
Understanding the regulatory landscape of human genome is a long-standing objective modern biology. Using reference-free alignment across 241 mammalian genomes produced by Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million candidate cis-regulatory elements (cCREs) and 15.6 transcription factor binding sites (TFBSs). We identified 439,461 cCREs 2,024,062 TFBSs under constraint. Genes near constrained perform fundamental cellular processes, whereas genes...
Species persistence can be influenced by the amount, type, and distribution of diversity across genome, suggesting a potential relationship between historical demography resilience. In this study, we surveyed genetic variation single genomes 240 mammals that compose Zoonomia alignment to evaluate how effective population size (
Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent functionally conserved despite low sequence conservation. We developed Tissue-Aware Conservation Inference Toolkit (TACIT) associate candidate with species' using predictions from machine learning...
Conserved genomic sequences disrupted in humans may underlie uniquely human phenotypic traits. We identified and characterized 10,032 human-specific conserved deletions (hCONDELs). These short (average 2.56 base pairs) are enriched for brain functions across genetic, epigenomic, transcriptomic datasets. Using massively parallel reporter assays six cell types, we discovered 800 hCONDELs conferring significant differences regulatory activity, half of which enhance rather than disrupt function....
Abstract Mast cells are the principal effector in IgE‐dependent hypersensitivity reactions. Despite reports that rodent mast proliferate presence of nerve growth factor (NGF), human reportedly do not respond to this factor. To determine if express NGF receptors, TrkA tyrosine receptor and low affinity (LNGFR), we first analyzed mRNA expression by RT‐PCR LNGFR a cell line (HMC‐1) cultured stem Both HMC‐1 were found but LNGFR. protein was demonstrated Western blot analysis lysates. Using flow...
Abstract Efficient 3D cell systems for neuronal induction are needed future use in tissue regeneration. In this study, we have characterized the ability of neural stem/progenitor cells (NS/PC) to survive, proliferate, and differentiate a collagen type I‐hyaluronan scaffold. Embryonic, postnatal, adult NS/PC were seeded present scaffold cultured medium containing epidermal growth factor fibroblast factor‐2, condition that stimulates proliferation. Progenitor from embryonic brain had highest...
Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding pathogenetic mechanisms and patient stratification. Concurrently, role immune cells microenvironment has received increasing attention, especially T tumor-associated macrophages (TAM). The latter are mixed population activated brain-resident microglia infiltrating...
Abstract Osteosarcoma is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of osteosarcoma spontaneously occurs in dogs, its differential incidence observed across breeds allows for the investigation tumor mutations context multiple genetic backgrounds. Using whole-exome sequencing dogs from three susceptible (22 golden retrievers, 21 Rottweilers, 23 greyhounds), we found tumors show high frequency somatic copy-number alterations (SCNA),...
Decrypting the rearrangements that drive mammalian chromosome evolution is critical to understanding molecular bases of speciation, adaptation, and disease susceptibility. Using 8 scaffolded 26 chromosome-scale genome assemblies representing 23/26 mammal orders, we computationally reconstructed ancestral karyotypes syntenic relationships at 16 nodes along phylogeny. Three different reference genomes (human, sloth, cattle) phylogenetically distinct superorders were used assess bias in expand...
Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (
Identifying external signals involved in the regulation of neural stem cell proliferation and differentiation is fundamental to understanding CNS development. In this study we show that platelet-derived growth factor (PDGF) can act as a mitogen for precursor cells. Multipotent cells from developing be maintained proliferative state under serum-free conditions presence fibroblast factor-2 (FGF2) induced differentiate into neurons, astrocytes, oligodendrocytes on withdrawal mitogen. PDGF has...
Abstract Glioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics preferentially linked GBM cancer stem cells (GSC), but how GSCs maintain their stemness incompletely understood the subject of intense investigation. Here, we identify novel signaling loop that induces maintains consisting an atypical metalloproteinase, ADAMDEC1, secreted by GSCs. ADAMDEC1 rapidly...
Glioblastoma (GBM) has one of the worst 5-year survival rates all cancers. While genomic studies disease have been performed, alterations in non-coding regulatory regions GBM largely remained unexplored. We apply whole-genome sequencing (WGS) to identify mutations, with potential GBM, under hypothesis that evolutionary constraint are likely be functional, and somatic mutations more damaging than unconstrained regions.
Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has hampered by lack technologies. Here, we adapted retrograde tracing using rabies viruses investigate and manipulate neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain, engaging in widespread functional communication, cholinergic driving...
Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, characterized by aggressive growth and a dismal prognosis. Interleukin-33 (IL-33) its receptor ST2 have emerged as regulators of glioma growth, but their exact function tumorigenesis not been deciphered. Indeed, previous studies on IL-33 cancer yielded somewhat opposing results to whether it pro- or anti-tumorigenic. Methods expression was assessed GBM tissue microarray public databases. As...