Biology subjects

Golob-Schwarzl, N.

Publications and source records attributed to Golob-Schwarzl, N..

3 recordsLinked to original sources

bioRxiv2026

A metabolic perspective on eIF1A and eIF3B inhibition as a potential therapeutic strategy in psoriasis

Psoriasis is a chronic inflammatory skin disease marked by epidermal hyperplasia and distinct metabolic alterations. Here, we investigated the metabolic impact of targeting translation initiation factors by performing 1H NMR-based metabolomic profiling on polar skin extracts from imiquimod-induced (IMQ) and K5.TGF{beta}1 transgenic (TGF{beta}) mouse models treated with eIF1A or eIF3B siRNA. IMQ-treated skin demonstrated significant, human-like metabolic shifts, including depleted energy substrates (glucose, glycogen, 3-hydroxybutyrate) and elevated phospholipid/nucleotide markers, which correlated strongly with epidermal thickness. In contrast, TGF{beta} skin exhibited no broad baseline polar metabolome changes. eIF1A/eIF3B inhibition selectively attenuated IMQ-associated energy and phospholipid alterations without causing widespread metabolic disruption in TGF{beta} skin. Overall, eIF1A/eIF3B inhibition ameliorated psoriasis-like pathology and mitigated disease-associated metabolic demands in a context-dependent manner.

molecular biology↗

bioRxiv2024

Inhibition of eukaryotic translation initiation factor 1A (eIF1A) and 3B (eIF3B) diminishes the psoriatic phenotype in two mouse models and human 3D model samples

BackgroundPsoriasis is a systemic inflammatory disease for which new topical treatments are required. Psoriatic inflammation is associated with overexpression of eukaryotic translation initiation factors (eIFs), which critically regulate gene expression in many important cellular processes, including proliferation, apoptosis, and differentiation. However, the exact link between overexpression of eIF and psoriasis is unknown. Here, we investigated the role of eIFs, particularly eIF1A and eIF3B, and the impact of their inhibition on the pathophysiology of psoriasis. MethodsWe used two mouse models reflecting the pathophysiology of psoriasis: (i) BALB/c mice topically treated with the immune activator imiquimod (IMQ) and (ii) K5.TGF{beta} transgenic mice. eIF1A and eIF3B were inhibited by either topical or systemic application of specific small interfering RNA (siRNA). In addition, we employed commercial human 3D psoriatic skin model samples. Importantly, in situ mRNA detection-based padlock probes against transcript variants of eIF1A und eIF3B was performed. ResultsTopical and systemic inhibition of eIF1A and eIF3B inhibited inflammation in both imiquimod and TGF{beta} mouse models as well as in a human 3D psoriasis model. Downregulation of eIF1A and eIF3B was associated with normalization of cell proliferation, restoration of the inflammatory milieu and epidermal hyperplasia of psoriasis, and normalization of levels of proinflammatory cytokines (e.g., TNF, IL-1b, IL-17, and IL-22) and keratinocyte differentiation markers (e.g., KRT16 and FLG). ConclusionThese results reveal an imbalance in translation and emphasize the crucial role of eIF1A and eIF3B in the pathophysiology of psoriasis. Targeting eIFs opens new avenues for the development of novel therapeutic treatment strategies against psoriasis.

molecular biology↗

bioRxiv2021

Identification of a Nervous System Gene Expression Signature in Colon Cancer Stem Cells Reveals a Role for Neural Crest Regulators EGR2 and SOX2 in Tumorigenesis

Recent data support a hierarchical model of colon cancer driven by a population of cancer stem cells (CSCs). Greater understanding of the mechanisms that regulate CSCs may therefore lead to more effective treatments. Serial limiting dilution xenotransplantation assays of colon cancer patient-derived tumors demonstrated ALDHPositive cells to be enriched for tumorigenic self-renewing CSCs. In order to identify CSC modulators, we performed RNA-sequencing analysis of ALDHPositive CSCs from a panel of colon cancer patient-derived organoids (PDOs) and xenografts (PDXs). These studies demonstrated CSCs to be enriched for embryonic and neural development gene sets. Functional analyses of genes differentially expressed in both ALDHPositive PDO and PDX CSCs demonstrated the neural crest stem cell (NCSC) regulator and wound response gene EGR2 to be required for CSC tumorigenicity and to control expression of homeobox superfamily embryonic master transcriptional regulator HOX genes and the embryonic and neural stem cell regulator SOX2. In addition, we identify EGR2, HOXA2, HOXA4, HOXA5, HOXA7, HOXB2, HOXB3 and the tumor suppressor ATOH1 as new prognostic biomarkers in colorectal cancer.

cell biology↗