A5013744530- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Colorectal Cancer Treatments and Studies
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Brain Metastases and Treatment
- Cancer Cells and Metastasis
- Biochemical and Molecular Research
- Cancer Research and Treatments
- Synthesis and biological activity
- Mechanisms of cancer metastasis
- RNA Research and Splicing
- Cancer, Stress, Anesthesia, and Immune Response
- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- Monoclonal and Polyclonal Antibodies Research
- Proteoglycans and glycosaminoglycans research
- Tuberculosis Research and Epidemiology
- Peptidase Inhibition and Analysis
Yale University
2015-2024
Yale Cancer Center
2019-2024
University of New Haven
2019-2024
Albert Einstein College of Medicine
2015-2019
Institute for Research in Biomedicine
2010-2018
Municipal Institute for Medical Research
2015
Pompeu Fabra University
2015
Hospital del Mar Research Institute
2015
Institució Catalana de Recerca i Estudis Avançats
2010
Hospital Clínic de Barcelona
2010
Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment distant metastases. Additionally, the acquisition invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for evolution neoplastic into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate bladder cell lines to better understand relationship between TIC EMT...
Tumor angiogenesis gets nervous The microenvironment of solid tumors hosts many intercellular conversations that can either enhance or inhibit tumor growth. Interestingly, the cells need not be direct participants in these conversations. Zahalka et al. studied genetically manipulated mouse models and found adrenergic signals from autonomic nerves prostate cancer fueled growth by altering metabolism blood vessel endothelial (see Perspective Hayakawa Wang). These nerve-derived suppressed...
How HSCs populate the fetal liver Hematopoietic stem cells (HSCs) undergo dramatic expansion in before migrating to their definitive site bone marrow. Khan et al. identify portal vessel–associated Nestin + NG2 pericytes as critical HSC niche components (see Perspective by Cabezas-Wallscheid and Trumpp). The vessel expand according fractal geometries, suggesting that cells—rather than factors expressed niche—drive proliferation. After birth, arterial vessels transform into veins, lose...
Background:There are currently no biomarkers for early breast cancer patient populations at risk of bone metastasis. Identification mediators metastasis could be clinical interest.
The majority of EGFR mutant lung adenocarcinomas respond well to tyrosine kinase inhibitors (TKI). However, most these responses are partial, with drug-tolerant residual disease remaining even at the time maximal response. This can ultimately lead relapses, which eventually develop in patients. To investigate cellular and molecular properties tumor cells vivo, we leveraged patient-derived xenograft (PDX) models cancer. Subcutaneous PDXs were treated third-generation TKI osimertinib until...
Abstract Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression a network extracellular matrix (ECM) molecules and their interacting proteins contributes risk in distinct LUAD subtypes. Overexpression hyaluronan receptor HMMR primary was associated with an inflammatory molecular signature poor prognosis. Attenuating cells diminished ability initiate tumors distant metastases. upregulation...
Highlights•BMX-seq reveals the tumor and stromal transcriptomes of brain metastasis in situ•The microenvironment reversibly activates neuronal-like genes cells•Increase microglial-bound TIM3 is a neuroinflammatory marker metastases•Different cancers that form share common transcriptomic hallmarksSummaryThe major site relapse for several cancers, yet deciphering mechanisms remains challenge because complexity (TME). To define molecular landscape from intact tissue vivo, we employ an...
Abstract Background Few somatic mutations have been linked to breast cancer metastasis, whereas transcriptomic differences among primary tumors correlate with incidence of especially the lungs and brain. However, epigenomic alterations transcription factors (TFs) which underlie these remain unclear. Methods To identify these, we performed RNA-seq, Chromatin Immunoprecipitation sequencing (ChIP-seq) Assay for Transposase-Accessible using (ATAC-seq) MDA-MB-231 cell line its brain (BrM2) lung...
Abstract The brain is a major sanctuary site for metastatic cancer cells that evade systemic therapies. Through pre-clinical pharmacological, biological, and molecular studies, we characterize the functional link between drug resistance central nervous system (CNS) relapse in Epidermal Growth Factor Receptor- (EGFR-) mutant non-small cell lung cancer, which can progress when treated with CNS-penetrant EGFR inhibitor osimertinib. Despite widespread osimertinib distribution vivo, microvascular...
Metastatic breast cancer remains a major cause of cancer-related deaths in women, and there are few effective therapies against this advanced disease. Emerging evidence suggests that key steps tumor progression metastasis controlled by reversible epigenetic mechanisms. Using an vivo genetic screen, we identified WDR5 as actionable regulator is required for metastatic models triple-negative cancer. We found knockdown cells independently impaired their tumorigenic well capabilities....
Abstract Tumor progression requires ablation of suppressor functions mediated by transforming growth factor β (TGFβ) signaling and oncogene-induced senescence (OIS), but how these are canceled in specific subtypes breast cancer remains unknown. In this study, we show that HER2-overexpressing cells avert TGFβ- OIS-mediated tumor suppression switching expression 2 functionally distinct isoforms the transcription C/EBPβ, which has been implicated previously development. HER2 activates...
Discordant responses between brain metastases and extracranial tumors can arise from branched tumor evolution, underscoring the importance of profiling mutations to optimize therapy. However, morbidity biopsies limits their use. We investigated whether cell-free DNA (cfDNA) in CSF could serve as an effective surrogate marker for genomic intraparenchymal (IP) metastases.CSF blood were collected simultaneously patients with progressive undergoing a craniotomy or lumbar puncture. Mutations both...
The integrated stress response (ISR) is a conserved pathway that activated by cells are exposed to stress. In lung adenocarcinoma, activation of the ATF4 branch ISR certain oncogenic mutations has been linked regulation amino acid metabolism. present study, we provide evidence for across multiple stages and molecular subtypes human adenocarcinoma. extracellular limitation, adenocarcinoma with diverse genotypes commonly induce in an eIF2α-dependent manner, which can be blocked...
Abstract Lineage selective transcription factors (TFs) are important regulators of tumorigenesis, but their biological functions often context dependent with undefined epigenetic mechanisms action. In this study, we uncover a conditional role for the endodermal and pulmonary specifying TF GATA6 in lung adenocarcinoma (LUAD) progression. Impairing Gata6 genetically engineered mouse models reduces proliferation increases differentiation Kras mutant LUAD tumors. These effects influenced by...
In the prostate, stem and progenitor cell regenerative capacities have been ascribed to both basal luminal epithelial cells. Here, we show that a rare subset of mesenchymal cells in prostate are epithelial-primed Nestin-expressing (EPNECs) can generate self-renewing organoids with bipotential capacity. Upon transplantation, these EPNECs form gland tissue grafts at clonal level. Lineage-tracing analyses marked by Nestin or NG2 transgenic mice contribute epithelium during organogenesis. adult,...
Lung cancer is a deadly treatment refractory disease that biologically heterogeneous.To understand and effectively treat the full clinical spectrum of thoracic malignancies, additional animal models can recapitulate diverse human lung subtypes stages are needed.Allograft or xenograft versatile enable quantification tumorigenic capacity in vivo, using malignant cells either murine origin.However, previously described methods cell engraftment have been performed non-physiological sites, such...
INTRODUCTION: Radiation necrosis (RN), a common and morbid side effect of radiosurgical treatment brain metastasis, is becoming more prevalent as immunotherapy options patient survival improve. Thought to be immunologically driven, the pathophysiology RN remains poorly defined. Further, often indistinguishable from regrowing metastases after stereotactic radiosurgery (SRS), requiring invasive biopsy for diagnosis. METHODS: We collected 20 intraoperative samples patients undergoing craniotomy...