A5027481752- Lung Cancer Research Studies
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Neuroendocrine Tumor Research Advances
- Brain Metastases and Treatment
- Cancer-related Molecular Pathways
- Hepatocellular Carcinoma Treatment and Prognosis
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Enzyme function and inhibition
- Peroxisome Proliferator-Activated Receptors
- Computational Drug Discovery Methods
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- RNA modifications and cancer
- SARS-CoV-2 detection and testing
- Polyamine Metabolism and Applications
- DNA Repair Mechanisms
- Genomic variations and chromosomal abnormalities
- Immune cells in cancer
Stanford University
2019-2025
Pediatrics and Genetics
2019-2024
University of Ioannina
2024
BioMed X Institute
2023
European Molecular Biology Laboratory
2015-2020
Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade the 'don't-eat-me' cell-surface molecule CD47 in small cell lung (SCLC), highly metastatic form cancer. potently enhances local antitumor effects preclinical models SCLC. Notably, also stimulates off-target 'abscopal' inhibiting non-irradiated SCLC tumors mice receiving radiation. These abscopal are independent T cells require macrophages that...
A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack suitable model systems, mechanistic basis has remained elusive. We developed an integrative method termed "complex alterations after selection and transformation (CAST)," enabling efficient vitro generation complex including chromothripsis, using cell perturbations...
Abstract The Notch pathway is a conserved cell-cell communication that controls cell fate decisions. Here we sought to determine how activation inhibits the neuroendocrine in lungs, an archetypal process for decisions orchestrated by signaling has remained poorly understood at molecular level. Using intratumoral heterogeneity small-cell lung cancer as tractable model system, uncovered role transcriptional regulators REST and YAP promoters of non-neuroendocrine transition. We further...
Abstract Small-cell lung cancer (SCLC) is an aggressive form of with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few known to promote the development SCLC. Here, we investigated contribution MAPK module MEK5–ERK5 SCLC growth. MEK5 and ERK5 were required for optimal expansion cell lines in vitro vivo. Transcriptomics analyses identified a role axis metabolism cells, including lipid metabolism. In-depth lipidomics showed that loss...
4-hydroxybenzoic acid (4-HBA) is an aromatic compound with high chemical stability, being extensively used in food, pharmaceutical and cosmetic industries therefore widely distributed various environments. Bioremediation constitutes the most sustainable approach for removal of 4-hydroxybenzoate its derivatives (parabens) from polluted Pseudarthrobacter phenanthrenivorans Sphe3, a strain capable degrading several compounds, able to grow on 4-HBA as sole carbon energy source. Here, attempt...
Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response treatment. Current technologies are still largely unsuitable accurately track phenotypes clonal evolution within tumors, especially in genetic manipulations. Here, we developed epitopes for imaging using combinatorial tagging (EpicTags), which coupled multiplexed ion beam (EpicMIBI) situ tracking barcodes tissue microenvironments. Using EpicMIBI, dissected the spatial component cell...
TP53 deficiency is the most common alteration in cancer; however, this alone typically insufficient to drive tumorigenesis. To identify genes promoting tumorigenesis combination with deficiency, we perform genome-wide CRISPR-Cas9 knockout screens coupled proliferation and transformation assays isogenic cell lines. Loss of several known tumor suppressors enhances cellular transformation. neddylation pathway promotes uncontrolled exclusively TP53-deficient cells. Combined loss CUL3 activates...
The ATR kinase is a master regulator of the cellular response to DNA replication stress. Activation relies on dual pathways involving TopBP1 and ETAA1 proteins, both which harbor ATR-activating domains (AADs). However, exact contribution recently discovered pathway signaling in different contexts remains poorly understood. Here, using an unbiased CRISPR-Cas9–based genome-scale screen, we show that ATR-stimulating function becomes indispensable for cell fitness chromosome stability when...
Patients with small-cell lung cancer (SCLC) are in dire need of more effective therapeutic options. Frequent disruption the G1 checkpoint SCLC cells creates a dependency on G2/M to maintain genomic integrity. Indeed, pre-clinical models, inhibiting kinase WEE1 shows promise growth. However, toxicity and acquired resistance limit clinical effectiveness this strategy. Here, using CRISPR-Cas9 knockout screens vitro vivo, we identified multiple factors influencing response inhibitor AZD1775,...
The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms action normal and cancer cells remain only partly understood. Here, we describe new mouse model to investigate the consequences depletion re-activation vivo . In these mice, induction shRNA molecules targeting for knock-down results development...
Intratumoral variability is a seminal feature of human tumors contributing to tumor progression and response treatment. Current technologies are unsuitable accurately track phenotypes subclonal evolution within tumors, especially in genetic manipulations. Here, we developed epitope combinatorial tags (EpicTags), which coupled multiplexed ion beam imaging (EpicMIBI) for situ tracking barcodes tissue microenvironments. Using this platform, dissected the spatial component cell lineages...
Abstract TP53 , the most frequently mutated gene in human cancer, encodes a transcriptional activator that induces myriad downstream target genes. Despite importance of p53 tumor suppression, specific genes important for suppression remain unclear. Recent studies have identified p53-inducible Zmat3 as critical effector but many questions regarding its p53-dependence, activity across contexts, and mechanism alone cooperation with other To address these questions, we used Tuba-seq Ultra...
ABSTRACT Brain metastasis is a major cause of morbidity and mortality in cancer patients. Here we investigated mechanisms allowing small-cell lung (SCLC) cells to grow the brain. We show that SCLC undergo cell state transition towards neuronal differentiation during tumor progression metastasis, this mimicry critical for growth Mechanistically, re-activate astrocytes, which turn promote by secreting pro-survival factors such as SERPINE1. further identify Reelin, molecule important brain...
Abstract Serology testing is crucial for diagnostics and epidemiological surveillance. Traditional methods test one antigen at a time are costly large scale implementation. Here, we introduce scalable, cost-effective, multiplex serology immunoassay that uses mass cytometry to analyze polystyrene beads loaded with stable isotopes. Our approach can generate 18,840 unique barcoded enables high-throughput detection of antibodies in small volumes plasma. This scalable method allows simultaneous...
Intratumoral variability is a seminal feature of human tumors contributing to tumor progression and response treatment. Current technologies are unsuitable accurately track phenotypes subclonal evolution within tumors, especially in genetic manipulations. Here, we developed epitope combinatorial tags (EpicTags), which coupled multiplex ion beam imaging (EpicMIBI) for situ tracking barcodes tissue microenvironments. Using this platform, dissected the spatial components cell lineages xenograft...
<div>Abstract<p>Small-cell lung cancer (SCLC) is an aggressive form of with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few known to promote the development SCLC. Here, we investigated contribution MAPK module MEK5–ERK5 SCLC growth. MEK5 and ERK5 were required for optimal expansion cell lines <i>in vitro</i> vivo</i>. Transcriptomics analyses identified a role axis in metabolism cells, including lipid...