A5007882163- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Telomeres, Telomerase, and Senescence
- Gut microbiota and health
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Probiotics and Fermented Foods
- Epigenetics and DNA Methylation
- Radiomics and Machine Learning in Medical Imaging
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- HIV Research and Treatment
- Cancer Cells and Metastasis
- Cell Image Analysis Techniques
- Genetics, Aging, and Longevity in Model Organisms
- Genomic variations and chromosomal abnormalities
- Digital Imaging for Blood Diseases
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Chromatin Remodeling and Cancer
- Monoclonal and Polyclonal Antibodies Research
- AI in cancer detection
University of Chicago
2023-2025
University of Illinois Chicago
2024
University of Pennsylvania
2016-2019
Children's Hospital of Philadelphia
2016-2019
Johns Hopkins University
2012-2013
University of Michigan–Ann Arbor
2010
Global changes in chromatin organization and the cessation of transcription during mitosis are thought to challenge resumption appropriate patterns after mitosis. The acetyl-lysine binding protein BRD4 has been previously suggested function as a transcriptional "bookmark" on mitotic chromatin. Here, genome-wide location analysis erythroid cells, combined with data normalization peak characterization approaches, reveals that widely occupies However, removal from does not impair post-mitotic...
Abstract Heterogeneity of immune checkpoint blockade (ICB) response amongst cancer patients has a profound impact on cancer-related mortality. It is now well understood that immunotherapy efficacy and resistance relate to wide spectrum cellular non-cellular components in the tumor microenvironment (TME). Although only widely used ICB biomarker, PD-L1, treats TME cells as individual components, recent work possible biomarkers predictive have had success by considering interactions within TME,...
Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants in vivo TF binding and accessibility, we introduce an approach compares ChIP-seq DNase-seq data sets from genetically divergent murine erythroid cell lines. The impact discriminatory single-nucleotide on ChIP signal enables definition at single base resolution characteristics nuclear GATA1, TAL1, CTCF. We further develop a facile complementary...
Due to the energetic frustration of RNA folding, tertiary structured is typically characterized by a rugged folding free energy landscape where deep kinetic barriers separate numerous misfolded states from one or more native states. While most in vitro studies rely on (re)folding chemically and/or enzymatically synthesized its entirety, which frequently leads into traps, nature reduces complexity problem segmental, co-transcriptional starting 5′ end. We here have developed simplified,...
The widely expressed bromodomain and extraterminal motif (BET) proteins bromodomain-containing protein 2 (BRD2), BRD3, BRD4 are multifunctional transcriptional regulators that bind acetylated chromatin via their conserved tandem bromodomains. Small molecules target BET bromodomains being tested for various diseases but typically do not discern between family members. Genomic distributions partners of have been described, the basis differences in function within a given lineage remains...
Abstract The human gut microbiome contains many bacterial strains of the same species (‘strain-level variants’). Describing in a biologically meaningful way rather than purely taxonomically is an important goal but challenging due to genetic complexity strain-level variation. Here, we measured patterns co-evolution across >7,000 spanning tree-of-life. Using these as prior for studying hundreds commensal that isolated, sequenced, and metabolically profiled revealed widespread structure...
Abstract Heterogeneity of therapeutic response amongst cancer patients has a profound impact on cancer-related mortality. It been widely hypothesized that diversity in clinical outcomes is driven by variability tumor biology at scales ranging from inter-patient to inter-cellular. Indeed, the advent technologies describing microenvironment (TME) cellular resolution demonstrated TME organization heterogeneous with respect intra-tumor spatial location, body location (primary vs metastatic),...
Abstract The tumor microenvironment (TME) is an immensely complex ecosystem 1,2 . This complexity underlies difficulties in elucidating principles of spatial organization and using molecular profiling the TME for clinical use 3 Through statistical analysis 96 transcriptomic (ST-seq) datasets spanning twelve diverse types, we found a conserved distribution multicellular, transcriptionally covarying units termed ‘Spatial Groups’ (SGs). SGs were either dependent on hierarchical local context –...
<h3>Background</h3> The tumor microenvironment (TME) is an important cellular ecosystem. However, immense structural and compositional heterogeneity presents a significant challenge in distinguishing conserved properties of TME spatial organization from qualities that are tumor-specific. Through the application statistical interference models to diverse database transcriptomics datasets, we aimed identify biologically clinically meaningful for patient outcomes immune checkpoint blockade...
Hematoxylin and eosin (H&E) is a common inexpensive histopathology assay. Though widely used information-rich, it cannot directly inform about specific molecular markers, which require additional experiments to assess. To address this gap, we present
The unlimited growth of tumors requires telomere maintenance. Telomerase typically maintains telomeres. Yet some lack telomerase and instead use recombination‐based mechanisms for Yeast deleted multiple break‐induced replication (BIR) that can occur within the telomeres or subtelomeres. To study BIR in mammalian cells, we are using a mouse model, myc+mTR−/− generates B‐cell lymphomas lacking telomerase. Using this model detected subtelomere recombination examine quantify recombination,...