Publications by authors named "Zora Modrusan"
This study examined nine prominent commercially available single-cell RNA sequencing (scRNA-seq) kits across four technology groups. Each kit was characterized using peripheral blood mononuclear cells (PBMCs) from a single donor, which enabled consistent assessment of factors such as analytical performance, protocol duration and cost. The Chromium Fixed RNA Profiling kit from 10× Genomics, with its probe-based RNA detection method, demonstrated the best overall performance.
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- Macrophages are diverse cells that inhabit all body tissues, with specific types residing in organs and additional subtypes recruited during injury.
- A specific population of recruited macrophages, marked by certain gene expressions, has been linked to fibrosis in various injury and cancer models.
- Blocking Notch2 increases these macrophages in the lungs, but evidence suggests they actually help reduce fibrosis rather than cause it, highlighting their potential protective role during lung injuries.
Multiomic profiling of single cells by sequencing is a powerful technique for investigating cellular diversity. Existing droplet-based microfluidic methods produce many cell-free droplets, underutilizing bead barcodes and reagents. Combinatorial indexing on microplates is more efficient for barcoding but labor-intensive.
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- * Wnt signaling is often altered in colorectal cancer, and ATF6 serves as a novel facilitator in this process.
- * Targeting ATF6 could present a new therapeutic strategy for treating colorectal cancer.
Article Synopsis
- Advances in high-resolution mapping have revealed complex structures formed by enhancers and promoters, known as enhancer-promoter hubs or cliques, which play a role in gene regulation.
- This study identifies enhancer-promoter hubs in breast cancer, lymphoma, and leukemia, highlighting their formation at important oncogenes and transcription factors that could drive cancer development.
- The research also shows that changes in these hubs are linked to shifts in gene expression related to resistance against targeted cancer therapies, indicating their potential impact on both oncogenesis and treatment outcomes.
Article Synopsis
- Single-cell RNA sequencing typically uses short-read technology, which struggles to fully analyze RNA isoforms; long-read sequencing can detect these isoforms but has challenges like lower throughput and errors.
- The new method developed, called Single-cell Targeted Isoform Long-Read Sequencing (scTaILoR-seq), captures over a thousand targeted genes, enhancing the number of useful transcripts by 29 times.
- By applying scTaILoR-seq, researchers successfully analyzed RNA isoforms from ovarian cancer samples, uncovering 10,796 transcriptomes and revealing how genetic variations relate to different transcript structures in single cells.
NKG2D-bispecific enhances NK and CD8+ T cell antitumor immunity.
Cancer Immunol Immunother
August 2024
Article Synopsis
- Cancer immunotherapy has transformed oncology, but immune responses are often suppressed in solid tumors, necessitating new strategies for enhancing immune activity.
- Researchers focused on the co-stimulatory receptor NKG2D, abundant on CD8+ tumor-infiltrating lymphocytes in breast cancer, to develop bispecific antibodies (HER2-CRB) that target both NKG2D and HER2.
- The HER2-CRB improved NK and T cell function, leading to increased antitumor activity when used with other antibodies, suggesting promising combinatorial potential for clinical trials.
Article Synopsis
- * Researchers systematically mapped these hubs in breast cancer, lymphoma, and leukemia, discovering that they often cluster around key oncogenes and transcription factors linked to cancer development.
- * The study also revealed that changes in these enhancer-promoter hubs are associated with transcriptional shifts that contribute to drug resistance in specific blood cancers, indicating their dynamic nature and potential influence on cancer treatment outcomes.
Article Synopsis
- - The study highlights the lack of effective predictive biomarkers for metastatic clear cell renal cell carcinoma (ccRCC), a cancer treatable by various inhibitors, and introduces the Angioscore as a promising RNA-based measure for predicting response to anti-angiogenic therapies, despite challenges in clinical adoption due to factors like high cost and tumor heterogeneity.
- - A novel deep learning model is developed to estimate the Angioscore from histopathology slides, providing visualizations of vascular networks, which enhances its interpretability compared to traditional models.
- - The model demonstrates strong predictive capability, showing high correlation with the Angioscore in multiple cohorts and effectively predicting treatment responses, making it a potentially valuable tool for understanding angiogenesis in ccRCC at a
Article Synopsis
- Sarcomatoid dedifferentiation occurs in various renal cell carcinoma subtypes, including chromophobe RCC, leading to more aggressive disease and resistance to treatments, but increased response to immunotherapy.
- Research on ChRCC reveals that it can dedifferentiate into sarcomatoid, anaplastic, and glandular forms, which are all linked to enhanced aggressiveness and metastasis.
- Key mutations, like those in TP53 and PTEN, drive this dedifferentiation process, and specific genetic and molecular markers could help classify and diagnose these aggressive tumors more effectively.
Translocation renal cell carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed clear cell RCC driver) disrupted nephrogenesis and glomerular development, causing neonatal death, while the clear cell RCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as alveolar soft part sarcoma) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an epithelial-mesenchymal transition.
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- The study investigates the roles of all four mammalian Argonaute (AGO) proteins in microRNA (miRNA) activity and finds that only AGO2 is essential for miRNA function, while AGO1, AGO3, and AGO4 can be disregarded for this purpose.
- Instead of miRNA regulation, AGO1, AGO3, and AGO4 are shown to influence type 2 immunity through their role in splicing precursor mRNA in CD4 T helper lymphocytes.
- The research highlights a direct interaction between nuclear AGO3 and SF3B3, which is part of the splicing machinery, affecting mRNA splicing and specifically the Nisch gene isoforms, implicating
Article Synopsis
- - Focal segmental glomerulosclerosis (FSGS) is a prevalent cause of nephrotic syndrome, especially affecting African-Americans at a higher rate (24 cases per million) than European-Americans (5 cases per million).
- - A study investigated the genetics of FSGS using data from 726 cases and 13,994 controls, identifying known risk genes and discovering a new association with the complement receptor 1 gene.
- - The research highlighted a risk variant, rs17047661, which appears to influence FSGS differently across genetic backgrounds, suggesting that genetic factors related to immune response might play a role in the disease's development.
Article Synopsis
- Systemic sclerosis (SSc) interstitial lung disease (ILD) significantly contributes to health complications and mortality in SSc patients, with tocilizumab (TCZ) showing promise in slowing lung function decline.
- Transcriptome analysis of skin biopsies from clinical trials indicated a gene network connected to disease progression, particularly involving plasma cell (PC) gene expressions linked to the positive effects of TCZ treatment.
- Further investigations, including single-cell RNA sequencing, confirmed that PC signature genes are present in CD38 and CD138 positive cells in SSc lungs, suggesting these genes may play an important role in the progression of the disease and the therapeutic mechanisms of TCZ.
Article Synopsis
- Fragile X syndrome (FXS) results from a repression of the gene responsible for the Fragile X mental retardation protein (FMRP), which is vital for brain development.
- Research using induced pluripotent stem cells (IPSCs) from FXS patients and CRISPR-engineered FMR1 knock-out cells revealed decreased firing rates in neurons and changes in gene expression related to neuronal function.
- The study found that the absence of FMRP leads to significant transcriptional alterations from the neural progenitor stage, disrupting neuronal activity and differentiation, highlighting FMRP's essential role in brain formation.
Article Synopsis
- Rare changes in certain genes can cause eye problems that affect vision early on, but we don’t fully understand how this happens.
- Researchers noticed that a specific gene, called DRAM2, is found in many parts of the eye, and when it’s not working properly, it can lead to issues in different types of eye cells.
- Studying human eye cells and mice showed that when DRAM2 is missing, it can cause some cells to grow too much while other important cells start to die off, making eye diseases more complicated to understand.
Article Synopsis
- TGFβ signaling contributes to a lack of response to immune checkpoint therapies in advanced cancers, especially in tumors that exclude immune cells.
- The study highlights that TGFβ and PD-L1 hinder the growth and replenishment of effective CD8 T cells within tumors, keeping them dysfunctional.
- Combining therapies that block TGFβ and PD-L1 enhances the movement and effectiveness of CD8 T effector cells, while also transforming the tumor environment to be more supportive of the immune response, indicating the necessity of IFNγ signaling in this process.
Article Synopsis
- - Wnt ligands play a crucial role in activating specific receptors (Frizzled and Lrp5/6) to regulate stem cell functions across various species.
- - In lung alveoli, different types of cells express distinct Wnt receptors, with Fzd5 being essential for alveolar epithelial stem cell function, while fibroblasts rely on other Fzd receptors.
- - New findings reveal that both Fzd5 and Fzd6 can activate Wnt signaling in stem cells, with Fzd6 uniquely guiding airway-derived progenitors toward an alveolar identity, suggesting a strategy for lung injury recovery without increasing fibrosis.
Article Synopsis
- - The Hippo pathway, important for growth regulation, features YAP and TAZ proteins that can promote cancer cell growth when activated.
- - Researchers found a small molecule inhibitor, GNE-7883, that blocks YAP/TAZ interactions with TEAD proteins, reducing cancer cell proliferation and showing strong effects in tumor models.
- - GNE-7883 also helps overcome resistance to certain cancer therapies, indicating its potential for use in targeted cancer treatments and addressing therapy resistance.
Article Synopsis
- The immune phenotype of tumors plays a crucial role in predicting how well they will respond to immunotherapy, with immune-inflamed tumors typically having better responses due to high T cell infiltration.
- Not all inflamed tumors are effective against therapy, and tumors lacking T cells (immune desert) or pushing T cells to the edges (immune excluded) show even lower response rates.
- The new technique called skin tumor array by microporation (STAMP) allows researchers to study the development and dynamics of tumor immune phenotypes in real-time, revealing that local factors and T cell recruitment are key to understanding tumor rejection and therapy success.
Article Synopsis
- Stem cells play a crucial role in maintaining rapidly renewing tissues like blood and intestines, and mutations affecting their proliferation and differentiation can lead to serious health issues.
- Researchers conducted studies by genetically targeting Rho-kinases Rock1 and Rock2 in adult mice, discovering these enzymes are essential for the health of hematopoietic (blood-forming) and gastrointestinal systems.
- Mice lacking Rho-kinases experienced cell cycle arrest in blood progenitors and impaired gut epithelial renewal, highlighting the importance of these kinases for stem cell function and overall organ integrity.
Article Synopsis
- The study examines the relationship between intratumoral bacteria and colorectal cancer (CRC) features, focusing on gene expression and the presence of 74 types of bacteria in 807 CRC samples.
- It highlights that certain orally derived bacteria, including Fusobacterium spp., are more prevalent in specific tumor types like right-sided, microsatellite instability-high, and BRAF-mutant tumors.
- The findings indicate that Fusobacterium animalis is particularly associated with certain tumor pathways in mesenchymal CMS4 tumors, suggesting a complex interaction between specific bacteria and tumor biology.
Article Synopsis
- Cellular senescence and the senescence-associated secretory phenotype (SASP) are linked to aging and related diseases, negatively affecting tissue health through inflammation.
- The study uses intestinal organoids to demonstrate that SASP factors from senescent fibroblasts disrupt stem cell function, leading to impaired tissue regeneration.
- A specific protein, the secreted N-terminal domain of Ptk7, is identified as crucial in this process, activating signals that hinder stem cell differentiation and contribute to age-related tissue dysfunction.