Publications by authors named "Youngjun Ju"
Article Synopsis
- The spread of tumor cells to essential organs significantly contributes to cancer-related deaths.
- This process, known as metastasis, complicates the treatment and management of various cancers.
- Understanding the mechanisms behind this spread is crucial for developing better therapies to improve patient outcomes.
Tumors recycle glucocorticoids to drive Treg-mediated immunosuppression.
J Clin Invest
September 2023
Article Synopsis
- The tumor microenvironment suppresses antitumor immunity, making it challenging for the body to fight tumors.
- Glucocorticoids (GCs) are hormones produced by the adrenal glands that can become active again through an enzyme called 11β-HSD1 found in certain tumor cells.
- The study reveals that GCs boost the immunosuppressive abilities of CD4+ regulatory T cells, promoting tumor growth; thus, targeting GC recycling may enhance the effectiveness of treatments like immune checkpoint blockade.
Article Synopsis
- - The study investigates the differences in cancer drivers between primary and metastatic breast cancer using genetic techniques in female mice, focusing on mutations involving the Rb gene, which is often inactive in this type of cancer.
- - Researchers identified specific gene insertion sites (gCIS) that are linked to either primary tumors, metastases, or both, highlighting significant networks related to cancer progression, including a shared MET-RAS network and additional pathways for metastatic cancer.
- - Analysis of human clinical data reveals that certain genetic factors are more prevalent in primary tumors or metastases, suggesting targeted treatments that inhibit specific signaling pathways (like RB1, MET, and RHO) could help block tumor cell migration and improve outcomes for metastatic breast cancer patients.
Inactivated Strains That Express TcpA via the -139F Allele Induce Antibody Responses against TcpA.
J Microbiol Biotechnol
November 2022
Article Synopsis
- Cholera is a significant global health issue, and oral cholera vaccines (OCVs) are a key prevention strategy, with research suggesting the need to enhance their effectiveness against various cholera antigens beyond just O-antigen.
- Patients recovering from cholera develop specific antibody responses that are crucial for immunity, highlighting the importance of targeting antigens like TCP and CT in OCV development.
- Recent studies indicate that strains expressing the -139F allele can stimulate strong antibody responses in mice, making them promising candidates for improved inactivated OCVs that could lead to better protection against cholera.
The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses.
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- * In cell studies, phage EK99P-1 was effective in reducing ETEC K99-induced damage to the intestinal barrier and preventing the loss of tight junction proteins.
- * The phage treatment also decreased the secretion of inflammatory cytokines, suggesting it modulates immune responses, thus helping to reinforce intestinal health during ETEC K99 infection.
Article Synopsis
- - The study investigates the role of pRB phosphorylation in development and homeostasis using Rb and Rb knock-in mice with disrupted phosphorylation sites, revealing normal early development despite suppressed phosphorylation.
- - While Rb mice show minimal aging signs with telomere shortening, Rb mice experience more severe aging effects, including growth issues and diabetes, due to disrupted pancreatic cell function and increased DNA damage response.
- - Treatment with vitamin C as an epigenetic regulator shows potential to improve pancreatic cell re-entry into the cell cycle, reduce DNA damage, and alleviate diabetes symptoms, highlighting its importance in regulation and longevity.
Article Synopsis
- - The interaction strength of T cell receptors with self-ligands influences immune responses, but its specific mechanisms are not fully understood.
- - Naive CD8 T cells showcase variability and form three distinct subsets based on their reactions to type I interferon, leading to differences in gene expression and functionality.
- - CD5Ly6C cells show a stronger antigen-specific response during viral infections, resulting in better development into effector cells but fewer memory cells, revealing how self-reactivity impacts naive CD8 T cell diversity through type I interferon signaling.
Article Synopsis
- Naïve CD8 T cells remain in a quiescent, steady state, regulated by various intrinsic and extrinsic factors, but the exact mechanisms are still unclear.
- Researchers discovered that the transcription factor STAT1 is crucial for maintaining this quiescence, as mice lacking STAT1 had increased proliferation of naïve CD8 T cells, leading to more memory/activated phenotype cells.
- The increased activity in STAT1-deficient mice was linked to an alternative signaling pathway involving type I interferon and was distinct from the effects observed in mice lacking the interferon receptor (IFNR).
Article Synopsis
- Scrub typhus is caused by a trombiculid mite bite that infects humans, and pneumonia is commonly seen in affected patients.
- Researchers explored the effectiveness of intranasal vaccination with an outer membrane protein (OMPOT) to protect against this infection.
- The study found that this vaccination prompted strong immune responses and provided protective immunity against scrub typhus-related pneumonia in mice.
Early onset senescence and cognitive impairment in a murine model of repeated mTBI.
Acta Neuropathol Commun
May 2021
Article Synopsis
- * Using a mouse model, researchers found that 24 hours after repeated mTBI, there was a notable activation of DNA damage responses and altered cellular signaling, while by 7 days post-injury, markers of cellular aging (senescence) and neurodegenerative processes became apparent, alongside cognitive deficits.
- * The findings suggest that early cellular senescence following repeated mTBI may contribute to cognitive decline, indicating that targeting these senescence pathways could be a potential treatment strategy for post
Article Synopsis
- eEF2K is a key regulator in protein translation elongation and is being explored as a therapeutic target for triple negative breast cancer (TNBC).
- Inhibition of eEF2K, especially when combined with glutamine starvation or other treatments, significantly suppresses the growth of TNBC cell lines by impacting specific proteins like c-MYC and Cyclin D1.
- Proteomic analysis revealed that inhibiting eEF2K along with 4EBP1 led to changes in the cell's protein landscape, particularly affecting pathways related to the extracellular matrix and immune response, paving the way for new TNBC treatment strategies.
Article Synopsis
- Naive CD8 T cells in specific mouse strains lacking IL-2 receptors exhibit strong proliferation independent of antigens, primarily driven by elevated levels of common gamma-chain cytokines like IL-2, IL-7, and IL-15.
- * In a study, mice deficient in Janus kinase 3 (Jak3) also showed robust proliferation of transferred naive CD8 T cells, again reliant on IL-2, indicating that signaling through γ cytokines is crucial for this expansion.
- * The research highlights a unique immune environment in these mice, characterized by high serum IL-2 linked to activated CD4 T cells and compromised regulatory CD4 T cells, pointing to potential strategies for treating human genetic mutations affecting immune function.*
Article Synopsis
- * YK4 treatment helped reduce AD symptoms by suppressing key immune factors, leading to a decrease in harmful T-helper 2 (Th2) cells while promoting beneficial Th1 and regulatory T (Treg) cells.
- * The study highlights that YK4 enhances dendritic cell function and the production of certain cytokines, suggesting it may effectively reshape immune responses to alleviate AD symptoms.
Developing effective mucosal subunit vaccine for the Streptococcus pneumoniae has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against S.
View Article and Find Full Text PDFHighly sensitive phenol biosensor was developed by using well-dispersed carbon nanotubes (CNTs) in enzyme solution and adding CNTs in enzyme electrodes. First, the intact CNTs were dispersed in aqueous tyrosinase (TYR) solution, and TYR molecules were precipitated and crosslinked to prepare the sample of enzyme adsorption, precipitation and crosslinking (EAPC). EAPC exhibited 10.
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- - The study explored how different styles of family conflict resolution impact depression, analyzing data from 3,565 participants over an average follow-up of about 4 years.
- - Findings showed that negative family conflict resolution is significantly linked to higher odds of developing depressive symptoms, especially among women and those experiencing verbal or threatening behavior.
- - The results suggest a need for healthcare providers and policymakers to foster effective conflict resolution strategies within families to enhance mental health outcomes.
Article Synopsis
- CDC25 is a dual phosphatase that has been identified as a key target for various triple-negative breast cancers, especially those lacking certain genetic features.
- Inhibitors that block CDC25 show promising results when combined with PI3K inhibitors, leading to better suppression of tumor growth.
- The text highlights the potential of CDC25 inhibitors in cancer treatment while also addressing the challenges of making these treatments available in clinical settings.
Article Synopsis
- * In triple-negative breast cancer (TNBC), RB1 is often inactivated alongside PTEN and TP53, leading researchers to conduct inhibitor screens on cell lines that lack these tumor suppressors.
- * The study identified CDC25 phosphatase as a promising therapeutic target, showing that inhibiting CDC25 can suppress the growth of RB1-deficient TNBC cells, especially when combined with WEE1 and PI3K inhibitors.
Cystathionine gamma-lyase/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice.
Biochim Biophys Acta Mol Cell Biol Lipids
February 2018
Hydrogen sulfide (HS) has been recognized as an important gasotransmitter analogous to nitric oxide and carbon monoxide. Cystathionine gamma-lyase (CSE)-derived HS is implicated in the regulation of insulin resistance and glucose metabolism, but the involvement of CSE/HS system in energy homeostasis and fat mass has not been extensively explored. In this study, a potential functional role of the CSE/HS system in in vitro adipocyte differentiation and in vivo adipogenesis and the underlying mechanism was investigated.
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- A key feature of cancer is the switch from catabolic to anabolic metabolism, allowing for rapid cell growth, influenced by mutations like PIK3CA and loss of tumor suppressors such as TP53 and RB1.
- Tumor development relies on active mitochondrial function and oxidative phosphorylation (OXPHOS), which has been shown to be enhanced by RB1 loss in breast cancer.
- The paper suggests that targeting both anabolic metabolism and OXPHOS could provide a therapeutic strategy against aggressive tumors that utilize lethal combinations of oncogenes and tumor suppressors.
Protein -sulfhydration is a newly discovered post-translational modification of specific cysteine residue(s) in target proteins, which is involved in a broad range of cellular functions and metabolic pathways. By changing local conformation and the final activity of target proteins, -sulfhydration is believed to mediate most cellular responses initiated by H₂S, a novel gasotransmitter. In comparison to protein -sulfhydration, nitric oxide-mediated protein -nitrosylation has been extensively investigated, including its formation, regulation, transfer and metabolism.
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- The PTEN gene, a tumor suppressor, is often inactivated in breast cancer, which may require additional genetic events for tumor formation despite germ-line mutations leading to nonmalignant growths.
- Most tumors from PTEN deletion in mice are well-differentiated and do not contain transplantable tumor-initiating cells, except for a rare poorly differentiated type that does.
- Poorly differentiated tumors show unique genetic features and reduced levels of microRNA-143/145; when this microRNA is knocked down, it increases tumor formation by activating RAS signaling, which is linked to worse outcomes in patients, especially in basal-like breast cancer cases.
Electrospun and ethanol-dispersed polystyrene-poly(styrene-co-maleic anhydride) (PS-PSMA) nanofibers (NFs) were used as a platform for the selective capture and three-dimensional culture of EpCAM-positive cells in cell culture medium and whole blood. The NFs were treated with streptavidin to facilitate bond formation between the amino groups of streptavidin and the maleic anhydride groups of the NFs. A biotinylated anti-EpCAM monoclonal antibody (mAb) was attached to the streptavidin-conjugated NFs via the selective binding of streptavidin and biotin.
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- Continuous contact with self-MHC ligands is crucial for the survival of naïve T cells, while memory T cells do not require this.
- The study reveals that the sensitivity of T-cell receptors (TCR) decreases in memory CD8 T cells and correlates with higher levels of CD5, a marker associated with strong MHC reactivity.
- Increased CD45 expression on CD8 T cells is linked to lower TCR sensitivity, which may help prevent excessive responses to self-antigens while still allowing robust responses to foreign antigens.