A5084367439- Stress Responses and Cortisol
- DNA Repair Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Acute Myeloid Leukemia Research
- Neuroendocrine regulation and behavior
- Memory and Neural Mechanisms
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Neuroscience and Neuropharmacology Research
- Histone Deacetylase Inhibitors Research
- Genomics, phytochemicals, and oxidative stress
- Biochemical effects in animals
- Animal Behavior and Welfare Studies
- Folate and B Vitamins Research
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Animal testing and alternatives
- Protein Degradation and Inhibitors
- Peroxisome Proliferator-Activated Receptors
- Lymphoma Diagnosis and Treatment
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
Karolinska Institutet
2009-2023
Svenska Örtmedicinska Institute
2023
Science for Life Laboratory
2014-2022
Liverpool Hospital
2022
Pacific University Oregon
2018
Institute of Science and Technology Austria
2013
University of Michigan–Ann Arbor
2013
Karolinska University Hospital
2002
The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG because Ogg1-deficient mice are resistant acute systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention treatment inflammation. We developed TH5487, selective active-site inhibitor OGG1, which hampers binding repair well tolerated by...
Abstract The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role DNA replication genomic stability cells, perform drug screen to identify potent selective nanomolar inhibitors; protein cocrystal structures demonstrated binding active site of target...
Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked memory formation and storage, postulated this be required for memories. now show mice with inducible overexpression NgR1 forebrain neurons have normal long-term potentiation 24-h memory, but severely impaired month-long both passive avoidance swim maze tests. Blocking transgene expression...
Abstract Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target exploit reactive oxygen species (ROS) elevation cancer. Although depletion is well tolerated non-transformed cells, report here...
Social housing is the optimal way of female laboratory mice. However, individual may be required in experimental designs, for example after surgery. We therefore investigated whether two mice a cage, separated by grid partition ('living apart together', LAT), counters adverse effects on postoperative recovery. Ten individually housed (IND) mice, nine socially (SOC) and LAT, were surgically implanted with telemetry transmitter. From one week prior to surgery until three weeks thereafter,...
Small cell lung cancer (SCLC) is an aggressive disease with median survival of <2 years. Tumour biopsies for research are scarce, especially from extensive-stage patients, repeat sampling at progression rarely performed. We overcame this limitation relevant preclinical models by developing SCLC circulating tumour derived explants (CDX), which mimic the donor pathology and chemotherapy response. To facilitate compound screening identification clinically biomarkers, we developed short-term ex...
BackgroundOsteosarcoma (OS) is the most common primary malignant bone tumour. Unfortunately, no new treatments are approved and over last 30 years survival rate remains only 30% at 5 for poor responders justifying an urgent need of therapies. The Mutt homolog 1 (MTH1) enzyme prevents incorporation oxidized nucleotides into DNA recently developed MTH1 inhibitors may offer therapeutic potential as overexpressed in various cancers.MethodsThe aim this study was to evaluate benefits targeting...
Abstract Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, exhibiting high levels of reactive oxygen species (ROS). ROS have been suggested to drive leukemogenesis and thus a potential novel target for treating AML. MTH1 prevents incorporation oxidized nucleotides into the DNA maintain genome integrity upregulated in many cancers. Here we demonstrate that cancers are highly sensitive inhibitor TH1579 (karonudib). A functional precision medicine ex vivo screen primary AML...
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and generally caused by viral infections or consumption mutagens, such as alcohol. While transplantation hepatectomy curative for some patients, many relapse into disease with few treatment options tyrosine kinase inhibitors, example, sorafenib lenvatinib. The need novel systemic approaches urgent.MTH1 expression profile was first analyzed in a HCC database MTH1 mRNA/protein level determined resected paired paracancerous...
Recently, interest in the rat as an animal model of Alzheimer's disease (AD) has been growing. We have previously described Tg6590 transgenic line expressing amyloid precursor protein containing Swedish AD mutation (K670M/N671L) that shows early stages Abeta deposition, predominantly cerebrovascular blood vessels, after 15 months age. Here we show by age 9 months, is long before appearance deposits, rats exhibit deficits Morris water maze spatial navigation task and altered spontaneous...