Gavriel Fialkoff
A5032094269- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- SARS-CoV-2 detection and testing
- Biosensors and Analytical Detection
- Genomics and Phylogenetic Studies
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
- Neuroendocrine Tumor Research Advances
- Phagocytosis and Immune Regulation
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Advanced Proteomics Techniques and Applications
- Peptidase Inhibition and Analysis
- Extracellular vesicles in disease
- Molecular Biology Techniques and Applications
- Liver Diseases and Immunity
- SARS-CoV-2 and COVID-19 Research
- Blood disorders and treatments
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
Hebrew University of Jerusalem
2019-2023
Hadassah Medical Center
2020-2023
iRobot (United States)
2020
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine cancer. Oncogenic MYC amplifications drive SCLC heterogeneity, but the genetic mechanisms of amplification and phenotypic plasticity, characterized by nonneuroendocrine cell states, are not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA fluorescence in situ hybridization to find extrachromosomal (ecDNA) as a primary source oncogene driver fusions. ecDNAs bring proximity enhancer...
Strenuous physical exercise causes a massive elevation in the concentration of circulating cell-free DNA (cfDNA), which correlates with effort intensity and duration. The cellular sources physiological drivers this phenomenon are unknown. Using methylation patterns cfDNA associated histones, we show that originates mostly extramedullary polymorphonuclear neutrophils. Strikingly, cardiomyocyte increases after marathon, consistent elevated troponin levels indicating low-level, delayed cardiac...
A sequencing-based detection and genotyping assay for SARS-CoV-2 is based on early sample pooling using barcoded oligo hybridization.
Abstract Emerging data on small cell lung cancer (SCLC), an aggressive malignancy with exceptionally poor prognosis, support subtypes driven by distinct transcription regulators, which engender unique therapeutic vulnerabilities. However, the translational potential of these observations is limited access to tumor biopsies. Here, we leverage chromatin immunoprecipitation cell-free nucleosomes carrying active modifications followed sequencing (cfChIP-seq) 442 plasma samples from individuals...
Abstract: Genomic DNA is packed by histone proteins that carry a multitude of post-translational modifications reflect cellular transcriptional state. Cell-free (cfDNA) derived from fragmented chromatin in dying cells, and as such it retains the histones markings present cells origin. Here, we pioneer immunoprecipitation followed sequencing cell-free nucleosomes (cfChIP-seq) carrying active marks. Our results show cfChIP-seq provides multidimensional epigenetic information recapitulates...
Abstract Autoimmune hepatitis (AIH) is a self-perpetuating inflammatory liver disease with significant morbidity and mortality risks. Patients undergo biopsy to confirm diagnosis affirm subsequent remission. Advances in liquid biopsies show promise replace tissue cancer, however little research has been done disease. Here, we use plasma chromatin immunoprecipitation sequencing (cfChIP-seq) analyze cell-free nucleosomes carrying an active histone modification which reports on gene...
Abstract The full spectrum of tissues affected by SARS-CoV-2 infection is crucial for deciphering the heterogenous clinical course COVID-19. Here, we analyzed DNA methylation and histone modification patterns in circulating chromatin to assess cell type-specific turnover severe asymptomatic COVID-19 patients, relation outcome. Patients with had a massive elevation cell-free (cfDNA) levels, which originated lung epithelial cells, cardiomyocytes, vascular endothelial cells erythroblasts,...
Abstract The global SARS-CoV-2 pandemic created a dire need for viral detection tests worldwide. Most current are based on RNA extraction followed by quantitative reverse-transcription PCR assays. While automation and improved logistics increased the capacity of these tests, they cannot exceed lower bound dictated one RT-PCR reaction per sample. Multiplexed next generation sequencing (NGS) assays provide dramatic increase in throughput, hold promise richer information including strains, host...
<p>Amplicon design used for the targeted single-cell copy-number analysis. Normalized depth of MYC and MYCL amplicons in single-cells DMS-273 cell line are shown, as well comparison amplicon depths single cells between patient derived Adrenal gland (ecDNA+) Cerv.LN (HSR+) lines.</p>
The current SARS-CoV2 epidemic calls for large scale viral tests. testing procedure the presence of virions involves several steps - pharyngeal/nasal swab, cell/viral lysis, RNA extraction, and an rtPCR assay targeting genome a human gene as internal sample control. Improvement any these in terms cost, processing time, or reagent availability, could result significant increase capacity world-wide. Here, we describe rapid efficient home made SPRI-based extraction method from lysed sample. Our...
The global SARS-CoV-2 pandemic led to a steep increase in the need for viral detection tests worldwide. Most current are based on RNA extraction followed by quantitative reverse-transcription PCR assays that involve separate and qPCR reaction each sample with fixed cost time. While automation improved logistics can capacity of these tests, they cannot exceed this lower bound dictated one per sample. Multiplexed next generation sequencing (NGS) provide dramatic throughput, hold promise richer...
The global SARS-CoV-2 pandemic led to a steep increase in the need for viral detection tests worldwide. Most current are based on RNA extraction followed by quantitative reverse-transcription PCR assays that involve separate and qPCR reaction each sample with fixed cost time. While automation improved logistics can capacity of these tests, they cannot exceed this lower bound dictated one per sample. Multiplexed next generation sequencing (NGS) provide dramatic throughput, hold promise richer...
<p>Fusion analysis results calculated with STARfusion and summary of RLF exon1 exon2 expression for the CCLE cohort. Table summarizes RLF-MYCL qPCR results.</p>
<div>Abstract<p>Small-cell lung cancer (SCLC) is an aggressive neuroendocrine cancer. Oncogenic <i>MYC</i> amplifications drive SCLC heterogeneity, but the genetic mechanisms of amplification and phenotypic plasticity, characterized by nonneuroendocrine cell states, are not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA fluorescence <i>in situ</i> hybridization to find extrachromosomal (ecDNA) as a primary...
<p>Fusion landscape and ecDNA RLF-MYCL fusions, related to Figure 3.</p>
<p>ecDNA heterogeneity in SCLC, related to Figure 4</p>
<p>ecDNA in SCLC, related to Figure 1</p>
<p>Expression and copy-number status of recurrently highly amplified genes in patient cell line samples. The tables summarize signal AmpliconArchitect curation, expression key results the multivariate analysis.</p>
<p>Expression and copy-number status of recurrently highly amplified genes in patient cell line samples. The tables summarize signal AmpliconArchitect curation, expression key results the multivariate analysis.</p>
<p>ecDNA in SCLC, related to Figure 1</p>
<p>Amplified genes identified from cell-free ChIP-seq of patient plasma samples.</p>
<p>Heterogeneity in patient derived samples, related to Figure 5</p>