A5061894450- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Click Chemistry and Applications
- PARP inhibition in cancer therapy
- Histone Deacetylase Inhibitors Research
- Peroxisome Proliferator-Activated Receptors
- Autophagy in Disease and Therapy
- HIV/AIDS drug development and treatment
- Protein Degradation and Inhibitors
- HIV Research and Treatment
- HIV-related health complications and treatments
- Calcium signaling and nucleotide metabolism
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Gut microbiota and health
- Biochemical and Molecular Research
- RNA modifications and cancer
- HIV/AIDS Research and Interventions
- Ubiquitin and proteasome pathways
- Inflammatory mediators and NSAID effects
- Cancer-related gene regulation
- Lipid metabolism and biosynthesis
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
The Wistar Institute
2016-2025
ORCID
2021
Stanford University
2014
Institute of Immunological Engineering
1993
Turku Centre for Biotechnology
1993
Abstract Clinical trials repurposing lysosomotropic chloroquine (CQ) derivatives as autophagy inhibitors in cancer demonstrate encouraging results, but the underlying mechanism of action remains unknown. Here, we report a novel dimeric CQ (DC661) capable deacidifying lysosome and inhibiting significantly better than hydroxychloroquine (HCQ). Using an situ photoaffinity pulldown strategy, identified palmitoyl-protein thioesterase 1 (PPT1) molecular target shared across monomeric derivatives....
The composition of the gut microbiome can control innate and adaptive immunity has emerged as a key regulator tumor growth, especially in context immune checkpoint blockade (ICB) therapy. However, underlying mechanisms for how affects growth remain unclear. Pancreatic ductal adenocarcinoma (PDAC) tends to be refractory therapy, including ICB. Using nontargeted, liquid chromatography–tandem mass spectrometry–based metabolomic screen, we identified microbe–derived metabolite trimethylamine N...
A disruption of the crosstalk between gut and lung has been implicated as a driver severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts barrier integrity, increasing permeability to microbes their products. This exacerbates resulting in positive feedback. We aimed test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers disrupted permeability. applied multi-omic systems biology approach analyze plasma samples from...
People living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation partly attributed to intestinal microbial dysbiosis and translocation, which may lead non-AIDS-related aging-associated comorbidities. The extent - influenced by the infection itself, ART usage, sexual orientation, or other associated factors affects biological age of intestines unclear. Furthermore, role translocation in aging...
Older patients with melanoma (>50 years old) have poorer prognoses and response rates to targeted therapy compared young (<50 old), which can be driven, in part, by the aged microenvironment. Here, we show that dermal fibroblasts increase secretion of neutral lipids, especially ceramides. When cells are exposed fibroblast lipid secretome, or cocultured fibroblasts, they uptake lipids via fatty acid transporter FATP2, is upregulated microenvironment known play roles synthesis...
Long COVID, a type of post-acute sequelae SARS-CoV-2 (PASC), has been associated with sustained elevated levels immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from gut and/or lung) to blood. Whether contributes PASC is We did not observe significant elevation in plasma markers bacterial PASC. we observed higher fungal - measured as...
Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were required to achieve cytotoxic effect of DC661. Inhibition cathepsins, or iron calcium chelation, did rescue DC661-induced cytotoxicity. PPT1 induced lysosomal lipid peroxidation (LLP), which led membrane permeabilization...
G-protein-coupled receptors (GPCRs) are integral membrane proteins that initiate responses to extracellular stimuli by mediating ligand-dependent activation of cognate heterotrimeric G proteins. In yeast, occupancy GPCR Ste2 peptide pheromone α-factor initiates signaling releasing a stimulatory Gβγ complex (Ste4-Ste18) from its inhibitory Gα subunit (Gpa1). Prolonged pathway stimulation is detrimental, and feedback mechanisms have evolved act at the receptor level limit duration stimulate...
FUNDC1 regulates mitochondrial morphology, localization, and function to support cancer cell proliferation.
HIV-1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as determinant of susceptibility to infection, but its role in the development maintenance latency not elucidated. By combining transcriptomic, proteomic, metabolomic analyses, we here show that transition infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect....
Abstract Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such can improve the safety of analytic treatment (ATI) and provide mechanistic insights into host pathways involved in post-ART control. Here we report plasma glycomic metabolic signatures time-to-viral-rebound probability-of-viral-remission using samples from two independent cohorts. These include a large number post-treatment controllers, rare population...
Abstract Staining of blot membranes enables the visualization bound proteins. Proteins are usually transferred to by electroblotting, direct spotting protein solutions, or contact blots. allows efficiency transfer membrane be monitored. This unit describes protocols for staining proteins after electroblotting from polyacrylamide gels such as polyvinylidene difluoride (PVDF), nitrocellulose, nylon membranes. The same methods can used if directly spotted, either manually using robotics....
This article describes processing of protein samples using 1D SDS gels prior to protease digestion for proteomics workflows that subsequently utilize reversed-phase nanocapillary ultra-high-pressure liquid chromatography (LC) coupled tandem mass spectrometry (MS/MS). The resulting LC-MS/MS data are used identify peptides and thereby infer proteins present in ranging from simple mixtures very complex proteomes. Bottom-up proteome studies usually involve quantitative comparisons across several...
Although oncogenic NRAS activates mitogen-activated protein kinase (MAPK) signaling, inhibition of the MAPK pathway is not therapeutically efficacious in -mutant ( MUT ) tumors. Here, we report that selectively silencing ribosomal S6 2 (S6K2) while preserving activity S6K1 perturbs lipid metabolism, enhances fatty acid unsaturation, and triggers lethal peroxidation melanoma cells are resistant to inhibition. S6K2 depletion induces endoplasmic reticulum stress peroxisome...
During skeletal growth, there is an increased secretion of lactate by glycolytic nucleus pulposus (NP) cells the intervertebral disc. To investigate role this anion, we generated annulus fibrosus (AF) and endplate (EP) specific Mct1 cKO ( Slc16a1 Col2CreERT2 ) mice. Histological spatial transcriptomic studies indicated significant disc degeneration in , characterized NP cell loss delayed EP maturation. Metabolic assays showed that while AF were glycolytic, chondrocytes readily metabolized...
Abstract Transferring proteins from polyacrylamide gels onto retentive membranes is now primarily used for immunoblotting. A second application that was quite common up to about a decade ago electroblotting of N‐terminal and internal sequencing using Edman chemistry. This unit contains procedures variety membranes, including polyvinylidene difluoride (PVDF) nitrocellulose. In addition the commonly tank or wet transfer system, protocols are provided semidry dry systems. also describes eluting...
New plasma and tissue biomarkers of epithelial ovarian cancer (EOC) could improve early diagnosis post-diagnosis clinical management. Here we investigated staining secretion CLIC1 CLIC4 across EOC subtypes. are two promising previously showed were elevated in patient sera. Individually, or stained larger percentages malignant tumors all subtypes compared with CA125, particularly stage mucinous tumors. also benign but was limited to nuclei; whereas diffuse cellular stromal tumor cells. Both...
ABSTRACT A disruption of the crosstalk between gut and lung has been implicated as a driver severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts barrier integrity, increasing permeability to microbes their products. This exacerbates resulting in positive feedback. We aimed test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers disrupted permeability. applied multi-omic systems biology approach analyze plasma...