A5003135559- Advanced biosensing and bioanalysis techniques
- TGF-β signaling in diseases
- RNA Interference and Gene Delivery
- Advanced Biosensing Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Cancer-related gene regulation
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Sarcoma Diagnosis and Treatment
- Hereditary Neurological Disorders
- Hippo pathway signaling and YAP/TAZ
- Biotin and Related Studies
- Receptor Mechanisms and Signaling
- Fibroblast Growth Factor Research
- Environmental DNA in Biodiversity Studies
- GDF15 and Related Biomarkers
- Genetic factors in colorectal cancer
- Wnt/β-catenin signaling in development and cancer
- Histone Deacetylase Inhibitors Research
- Galectins and Cancer Biology
- Mesenchymal stem cell research
- Cancer, Hypoxia, and Metabolism
Uppsala University
2005-2022
Science for Life Laboratory
2014-2022
University of California, San Diego
2012-2016
Ludwig Cancer Research
2008-2014
University of California System
2014
Howard Hughes Medical Institute
2012
Ludwig Cancer Research
2008-2012
Abstract Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they no ability enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating (CPPs), can promote uptake macromolecules via endocytosis. overcoming rate-limiting step endosomal escape into remains a major challenge. Hydrophobic amino acid R groups are known play vital role in viral from endosomes. Here we utilize...
NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within pathway a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, negative regulator normal B cells. Strikingly, 13 these cases carried an identical 4-bp frameshift deletion, resulting truncated...
Signal transduction by transforming growth factor beta (TGFbeta) coordinates physiological responses in diverse cell types. TGFbeta signals via type I and II receptor serine/threonine kinases intracellular Smad proteins that regulate transcription. Strength duration of signaling is largely dependent on a negative-feedback program initiated during signal progression. We have identified an inducible gene target TGFbeta/Smad signaling, the salt-inducible kinase (SIK), which negatively regulates...
Transforming growth factor β (TGFβ) regulates many physiological processes and requires control mechanisms to safeguard proper timely action. We have previously described how negative regulation of TGFβ signaling is controlled by the serine/threonine kinase salt-inducible 1 (SIK1). SIK1 forms complexes with type I receptor inhibitory Smad7 down-regulates receptor. now demonstrate that induces levels via a direct transcriptional mechanism implicates Smad proteins, we mapped putative enhancer...
Gene knockout strategies, RNAi and rescue experiments are all employed to study mammalian gene function. However, the disadvantages of these approaches include: loss function adaptation, reduced viability overexpression that rarely matches endogenous levels. Here, we developed an knockdown/rescue strategy combines selectivity with a highly efficient CRISPR directed recombinant Adeno-Associated Virus (rAAV) mediated targeting approach introduce allele-specific mutations plus allele-selective...
Background Initiation, amplitude, duration and termination of transforming growth factor β (TGFβ) signaling via Smad proteins is regulated by post-translational modifications, including phosphorylation, ubiquitination acetylation. We previously reported that ADP-ribosylation Smads poly(ADP-ribose) polymerase 1 (PARP-1) negatively influences Smad-mediated transcription. PARP-1 known to functionally interact with PARP-2 in the nucleus enzyme glycohydrolase (PARG) can remove chains from target...
Singly and multiply modified synthetic siRNA oligonucleotides, containing isomorphic surrogate nucleobases, show high interference potency in cell culture, suggesting the highly RNA alphabet, based on a thieno[3,4-d]-pyrimidine core, is tolerated well by cellular silencing machinery.
Abstract Digital PCR provides high sensitivity and unprecedented accuracy in DNA quantification, but current approaches require dedicated instrumentation have limited opportunities for multiplexing. Here, we present an isothermal platform digital enumeration of reaction products multiplex via standard fluorescence microscopy. Circular strands, which may result from a wide range molecular detection reactions, are captured on streptavidin-coated surfaces hybridized biotinylated primers,...
Abstract Drugs are designed to bind their target proteins in physiologically relevant tissues and organs modulate biological functions elicit desirable clinical outcomes. Information about engagement at cellular subcellular resolution is therefore critical for guiding compound optimization drug discovery, probing resistance mechanisms targeted therapies samples. We describe a engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs used visualize measure...
Abstract Protein interactions and posttranslational modifications orchestrate cellular responses to e.g. cytokines drugs, but it has been difficult monitor these dynamic events in high-throughput. Here, we describe a semi-automated system for large-scale situ proximity ligation assays (isPLA), combining isPLA microtiter wells with automated microscopy computer-based image analysis. Phosphorylations are digitally recorded along subcellular morphological features. We investigated...
Abstract Drugs are designed to bind their target proteins in physiologically relevant tissues and organs modulate biological functions elicit desirable clinical outcomes. Information about engagement at cellular subcellular resolution is therefore critical for guiding compound optimization drug discovery, probing resistance mechanisms targeted therapies samples. We describe a engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs used visualize measure...