A5101748443- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Poetry Analysis and Criticism
- Bacterial Genetics and Biotechnology
- Chromatin Remodeling and Cancer
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Samuel Beckett and Modernism
- Protein Degradation and Inhibitors
- Folklore, Mythology, and Literature Studies
- Pancreatic and Hepatic Oncology Research
- French Literature and Poetry
- RNA Research and Splicing
- Language, Metaphor, and Cognition
- Religious Studies and Spiritual Practices
- Fractal and DNA sequence analysis
- Cultural History and Identity Formation
- Modernist Literature and Criticism
- Paranormal Experiences and Beliefs
- Bacteriophages and microbial interactions
- Single-cell and spatial transcriptomics
- Cancer Mechanisms and Therapy
Kempten University of Applied Sciences
2024
Institut für Notfallmedizin Allgäu
2024
University of California, San Francisco
2013-2022
College of St. Scholastica
2018-2022
Regis University
2021
Regis College
2021
University of Palestine
2018
California Institute of Technology
2012-2014
Lawrence Livermore National Laboratory
1996
University of Illinois System
1943
Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported, but its scale, impact and contribution to HCC development not clear. Here, we sequenced tumor nontumor genomes (>80× coverage) transcriptomes of four patients identified 255 sites. Increased sequencing 240× coverage revealed proportionally higher number Clonal expansion HBV-integrated hepatocytes was found specifically in samples. We observe...
Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole-genome sequencing transcriptome on 19 lung cell lines three tumor/normal pairs. Overall, our data show that line models exhibit similar mutation spectra human tumor samples. Smoker never-smoker samples distinguishable patterns mutations. A number epigenetic regulators, including KDM6A, ASH1L, SMARCA4, ATAD2, are frequently altered by...
Abstract Background Hepatocellular carcinoma (HCC) is a heterogeneous disease with high mortality rate. Recent genomic studies have identified TP53 , AXIN1 and CTNNB1 as the most frequently mutated genes. Lower frequency mutations been reported in ARID1A ARID2 JAK1 . In addition, hepatitis B virus (HBV) integrations into human genome associated HCC. Results Here, we deep-sequence 42 HCC patients combination of whole genome, exome transcriptome sequencing to identify mutational landscape...
The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid tug-of-war is unclear. Furthermore, couples histone octamer deformation to nucleosome sliding, but underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeFx that capture potential reaction intermediates. In one structure, residues near dyad and in H2A-H2B acidic patch, distal active protomer, appear disordered. disordered patch...
ISWI family chromatin remodeling motors use sophisticated autoinhibition mechanisms to control nucleosome sliding. Yet how the different autoinhibitory domains are regulated is not well understood. Here we show that an acidic patch formed by histones H2A and H2B of relieves imposed AutoN NegC regions human remodeler SNF2h. Further, single molecule FRET helps distance travelled per translocation event. We propose a model in which activates SNF2h providing landing pad for auto-inhibitory...
In eukaryotes, a first step towards the nuclear DNA compaction process is formation of nucleosome, which comprised negatively charged wrapped around positively histone protein octamer. Often, it assumed that complexation into nucleosome completely attenuates charge and hence electrostatic field generated by molecule. contrast, theoretical computational studies suggest retains strong, negative field. Despite their fundamental implications for chromatin organization function, these opposing...
DNA is subject to large deformations in a wide range of biological processes. Two key examples illustrate how such influence the readout genetic information: sequestering eukaryotic genes by nucleosomes and looping transcriptional regulation both prokaryotes eukaryotes. These kinds regulatory problems are now becoming amenable systematic quantitative dissection with powerful dialogue between theory experiment. Here, we use single-molecule experiment conjunction statistical mechanical model...
Large-scale DNA deformation is ubiquitous in transcriptional regulation prokaryotes and eukaryotes alike. Though much known about how transcription factors constellations of binding sites dictate where gene will occur, less the role played by intervening DNA. In this work we explore effect sequence flexibility on factor-mediated looping, drawing sequences identified nucleosome formation ligase-mediated cyclization assays as being especially favorable for or resistant to large deformations....
The bacterial transcription factor LacI loops DNA by binding to two separate locations on the simultaneously. Despite being one of best-studied model systems for transcriptional regulation, number and conformations loop structures accessible remain unclear, though importance multiple coexisting has been implicated in interactions between other cellular regulators gene expression. To probe this issue, we have developed a new analysis method tethered particle motion, versatile commonly used...
Significance Storage and retrieval of the genetic information in cells is a dynamic process that requires DNA to undergo dramatic structural rearrangements. One prominent but still incompletely understood example such rearrangements protein-mediated looping. Here, we use single-molecule biophysical technique show elasticity protein affects kinetics both loop formation and, unexpectedly, breakdown, develop theory based on polymer physics explain origin these observations. Our results...
As the chief informational molecule of life, DNA is subject to extensive physical manipulations. The energy required deform double-helical depends on sequence, and this mechanical code influences gene regulation, such as through nucleosome positioning. Here we examine sequence-dependent flexibility in bacterial transcription factor-mediated looping, a context for which role sequence remains poorly understood. Using suite synthetic constructs repressed by Lac repressor two well-known...
Abstract The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid tug-of-war is unclear. Furthermore, couples histone octamer deformation to nucleosome sliding, but underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeFx that capture reaction intermediates. In one structure, residues near dyad and in H2A-H2B acidic patch, distal active protomer, are disordered. disordered patch...
Aurora Leigh's Radical Youth:Derridean Parergon and the Narrative Frame in “A Vision of Poets” Stephanie L. Johnson (bio) With publication Leigh 1856, Elizabeth Barrett Browning not only offered readers a poetic work that rivaled Wordsworth's The Prelude innovation form content but also identified this as pinnacle her career. In dedication to cousin John Kenyon, she describes it "the most mature my works, one into which highest convictions upon Life Art have entered."1 Following lead,...