Dag Sehlin
Universitetslektor vid Institutionen för folkhälso- och vårdvetenskap; Molekylär geriatrik/ Rudbecklaboratoriet
- Telefon:
- 018-471 34 05
- E-post:
- Dag.Sehlin@pubcare.uu.se
- Besöksadress:
- Dag Hammarskjölds väg 20
- Postadress:
- Rudbecklaboratoriet
751 85 Uppsala
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Kort presentation
Biografi
Denna text finns inte på svenska, därför visas den engelska versionen.
Dag Sehlin is Associate Professor of Neurobiology at Uppsala University. His research is focused on understanding the molecular mechanisms behind Alzheimer's disease and using this knowledge for development of novel therapeutic and diagnostic applications. His group has generated antibodies that bind specifically to different forms of amyloid-beta, to be used for both therapeutic and diagnostic purposes. By engineering the antibodies into a bispecific format that takes advantage of a ‘Molecular Trojan horse’ strategy to enter the brain more efficiently, the group has pioneered antibody-based PET imaging of brain targets.
Dag Sehlin received his PhD in 2010 after a joint academic-industrial project at Uppsala University, BioArctic AB and Mabtech AB that resulted in development of the amyloid-beta protofibril specific antibody lecanemab, which was recently approved for treatment of Alzheimer's disease. After a post doc at Uppsala University he focused on development of strategies to deliver protein drugs into the brain, for which he received prizes from the Swedish Lundbeck foundation and the Swedish Alzheimer foundation. In 2018, he was appointed Associate Professor at Uppsala University. Dag has authored 60 scientific articles, has an h-index of 30 and holds patents describing antibody development and engineering for increased brain penetration.
Publikationer
Urval av publikationer
- Long-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer's disease (2023)
- ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer's disease with a bispecific, brain-penetrating fusion protein (2022)
- Transferrin Receptor Binding BBB-Shuttle Facilitates Brain Delivery of Anti-A beta-Affibodies (2022)
- Brain pharmacokinetics of mono- and bispecific amyloid-beta antibodies in wild-type and Alzheimer's disease mice measured by high cut-off microdialysis (2022)
- 11C-PiB and 124I-antibody PET provide differing estimates of brain amyloid-β after therapeutic intervention (2022)
- Reduction of alpha SYN Pathology in a Mouse Model of PD Using a Brain-Penetrating Bispecific Antibody (2022)
- Functionalization of Radiolabeled Antibodies to Enhance Peripheral Clearance for High Contrast Brain Imaging (2022)
- PET Imaging in Preclinical Anti-Aβ Drug Development (2022)
- The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation (2021)
- Brain pharmacokinetics of two BBB penetrating bispecific antibodies of different size (2021)
- SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-beta antibody in a mouse model of Alzheimer's disease (2020)
- Brain delivery of biologics using a cross-species reactive transferrin receptor 1 VNAR shuttle. (2020)
- Fluorine-18-Labeled Antibody Ligands for PET Imaging of Amyloid-β in Brain (2020)
- High detection sensitivity with antibody-based PET radioligand for amyloid beta in brain (2019)
- Engineered antibodies (2019)
- Antibody-Based In Vivo PET Imaging Detects Amyloid-beta Reduction in Alzheimer Transgenic Mice After BACE-1 Inhibition (2018)
- Efficient clearence of A beta protofibrils in A beta PP-transgenic mice treated with a brain-penetrating bifunctional antibody (2018)
- Bivalent Brain Shuttle Increases Antibody Uptake by Monovalent Binding to the Transferrin Receptor (2017)
- Pharmacokinetics, biodistribution and brain retention of a bispecific antibody-based PET radioligand for imaging of amyloid-beta (2017)
- A bispecific Tribody PET radioligand for visualization of amyloid-beta protofibrils - a new concept for neuroimaging (2017)
- Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease (2016)
- Specific Uptake of an Amyloid-beta Protofibril-Binding Antibody-Tracer in A beta PP Transgenic Mouse Brain (2013)
- Large Aggregates Are the Major Soluble Ab Species in AD Brain Fractionated with Density Gradient Ultracentrifugation (2012)
- Sensitive ELISA detection of amyloid-β protofibrils in biological samples (2007)
Senaste publikationer
- Amyloid-β deposits in human astrocytes contain truncated and highly resistant proteoforms (2024)
- Comparing in vitro affinity measurements of antibodies to TfR1 (2024)
- Altered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion (2024)
- Synthesis and evaluation of fluorine-18 labelled tetrazines as pre-targeting imaging agents for PET (2024)
- Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody (2023)
Alla publikationer
Artiklar
- Amyloid-β deposits in human astrocytes contain truncated and highly resistant proteoforms (2024)
- Comparing in vitro affinity measurements of antibodies to TfR1 (2024)
- Altered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion (2024)
- Synthesis and evaluation of fluorine-18 labelled tetrazines as pre-targeting imaging agents for PET (2024)
- Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody (2023)
- Long-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer's disease (2023)
- Synaptic density in aging mice measured by [18F]SynVesT-1 PET (2023)
- Development of the First Tritiated Tetrazine (2022)
- ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer's disease with a bispecific, brain-penetrating fusion protein (2022)
- Transferrin Receptor Binding BBB-Shuttle Facilitates Brain Delivery of Anti-A beta-Affibodies (2022)
- Brain pharmacokinetics of mono- and bispecific amyloid-beta antibodies in wild-type and Alzheimer's disease mice measured by high cut-off microdialysis (2022)
- 11C-PiB and 124I-antibody PET provide differing estimates of brain amyloid-β after therapeutic intervention (2022)
- Passive and receptor mediated brain delivery of an anti-GFAP nanobody (2022)
- A Brain-Targeting Bispecific-Multivalent Antibody Clears Soluble Amyloid-Beta Aggregates in Alzheimer's Disease Mice (2022)
- Blood-brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer’s disease (2022)
- Reduction of alpha SYN Pathology in a Mouse Model of PD Using a Brain-Penetrating Bispecific Antibody (2022)
- In vivo imaging of alpha-synuclein with antibody-based PET (2022)
- Functionalization of Radiolabeled Antibodies to Enhance Peripheral Clearance for High Contrast Brain Imaging (2022)
- PET Imaging in Preclinical Anti-Aβ Drug Development (2022)
- Pretargeted Imaging beyond the Blood-Brain Barrier-Utopia or Feasible? (2022)
- The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid beta fibril formation (2021)
- Brain pharmacokinetics of two BBB penetrating bispecific antibodies of different size (2021)
- Pinpointing Brain TREM2 Levels in Two Mouse Models of Alzheimer's Disease (2021)
- Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta (2021)
- Enhanced neprilysin-mediated degradation of hippocampal A beta 42 with a somatostatin peptide that enters the brain (2021)
- In vivo imaging of synaptic density with [C-11]UCB-J PET in two mouse models of neurodegenerative disease (2021)
- Extracellular vesicles from amyloid-beta exposed cell cultures induce severe dysfunction in cortical neurons (2020)
- SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-beta antibody in a mouse model of Alzheimer's disease (2020)
- Chemical imaging of evolving amyloid plaque pathology and associated A β peptide aggregation in a transgenic mouse model of Alzheimer's disease (2020)
- Brain delivery of biologics using a cross-species reactive transferrin receptor 1 VNAR shuttle. (2020)
- Fluorine-18-Labeled Antibody Ligands for PET Imaging of Amyloid-β in Brain (2020)
- Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus (2019)
- High detection sensitivity with antibody-based PET radioligand for amyloid beta in brain (2019)
- Heterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls (2019)
- Pyroglutamation of amyloid-βx-42 (Aβx-42) followed by Aβ1–40 deposition underlies plaque polymorphism in progressing Alzheimer's disease pathology (2019)
- Engineered antibodies (2019)
- Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease (2019)
- Secretion and uptake of α-synuclein via extracellular vesicles in cultured cells (2018)
- Blood-Brain Barrier Integrity in a Mouse Model of Alzheimer’s Disease With or Without Acute 3D6 Immunotherapy (2018)
- Antibody-Based In Vivo PET Imaging Detects Amyloid-beta Reduction in Alzheimer Transgenic Mice After BACE-1 Inhibition (2018)
- Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer's Disease (2018)
- Efficient clearence of A beta protofibrils in A beta PP-transgenic mice treated with a brain-penetrating bifunctional antibody (2018)
- The A beta protofibril selective antibody mAb158 prevents accumulation of A beta in astrocytes and rescues neurons from A beta-induced cell death (2018)
- A small bispecific antibody-based construct based on bapineuzumab as a PET tracer for amyloid beta pathology in brain (2017)
- Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [(11)C]ABP688 PET imaging and ex vivo immunoblotting (2017)
- Efficient and inexpensive transient expression of multispecific multivalent antibodies in Expi293 cells (2017)
- Bivalent Brain Shuttle Increases Antibody Uptake by Monovalent Binding to the Transferrin Receptor (2017)
- Delineating Amyloid Plaque Associated Neuronal Sphingolipids in Transgenic Alzheimer's Disease Mice (tgArcSwe) Using MALDI Imaging Mass Spectrometry (2017)
- Pharmacokinetics, biodistribution and brain retention of a bispecific antibody-based PET radioligand for imaging of amyloid-beta (2017)
- Efficient clearance of Amyloid-beta protofibrils in APP-transgenic mice treated with a brain penetrating bifunctional antibody (2017)
- Cationization increases brain distribution of an amyloid-beta protofibril selective F(ab')2 fragment (2017)
- A bispecific Tribody PET radioligand for visualization of amyloid-beta protofibrils - a new concept for neuroimaging (2017)
- Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease (2016)
- Accumulation of amyloid-beta by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons (2016)
- Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons (2016)
- Increased Number of Plasma B Cells Producing Autoantibodies Against A beta(42) Protofibrils in Alzheimer's Disease (2015)
- Perspectives on future Alzheimer therapies (2014)
- Apolipoprotein E increases cell association of amyloid-β 40 through heparan sulfate and LRP1 dependent pathways (2014)
- Increased Inflammatory Response in Cytomegalovirus Seropositive Patients with Alzheimer's Disease (2014)
- Specific Uptake of an Amyloid-beta Protofibril-Binding Antibody-Tracer in A beta PP Transgenic Mouse Brain (2013)
- Large Aggregates Are the Major Soluble Ab Species in AD Brain Fractionated with Density Gradient Ultracentrifugation (2012)
- Heavy-Chain Complementarity-Determining Regions Determine Conformation Selectivity of Anti-A beta Antibodies (2011)
- Sensitive detection of A beta protofibrils by proximity ligation (2010)
- Interference from Heterophilic Antibodies in Amyloid-beta Oligomer ELISAs (2010)
- An amyloid-beta protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer's disease (2009)
- Sensitive ELISA detection of amyloid-β protofibrils in biological samples (2007)
- Astrocytes with Alzheimer’s disease pathology provoke lipid droplet mediated cell-to-cell propagation of MHC II complexes
- Stronger affinity to Transferrin receptor enhances detection of amyloid-β pathology with bispecific antibody radioligands at a tracer dose
- Evaluation of valency effects on TfR-mediated brain delivery in vivo
- Single domain antibody conjugated to Aβ-binding scFv penetrates BBB via TfR to interact with Aβ
- Therapeutic and diagnostic potential of a multivalent antibody against soluble amyloid-beta aggregates
- The Uppsala APP mutation promotes wildtype Aβ aggregation and deposition in vivo
- The Uppsala APP deletion causes early onset autosomal dominant Alzheimer’s disease by altering APP processing and increasing amyloid-β fibril formation
- Transgenic mice harboring the Uppsala APP mutation display altered APP processing and accelerated Aβ42 pathology with distinct structural features
- A brain-targeting bispecific-multivalent antibody clears soluble amyloid-beta aggregates in Alzheimer’s disease mice
- Reduced neonatal Fc receptor binding increases clearance and brain-to-blood ratio of a brain penetrating amyloid-β antibody
- Aβ targeting ImmunoPET
- [11C]PiB binding after treatment with an amyloid-beta antibody
- Synaptic density in aging mice measured by [18F]SynVesT-1 PET
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