A5036599953- Cancer, Hypoxia, and Metabolism
- Molecular Sensors and Ion Detection
- Brain Metastases and Treatment
- Analytical Methods in Pharmaceuticals
- Piperaceae Chemical and Biological Studies
- Metabolism, Diabetes, and Cancer
- Biochemical Analysis and Sensing Techniques
- Ion Channels and Receptors
- Genomics and Chromatin Dynamics
- Cancer-related cognitive impairment studies
- CRISPR and Genetic Engineering
- Histone Deacetylase Inhibitors Research
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- RNA Research and Splicing
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Analytical Chemistry and Sensors
- Food Security and Health in Diverse Populations
National Cancer Institute
2015-2025
Center for Cancer Research
2020-2025
National Institutes of Health
2016-2025
University of Guelph
2024
Johns Hopkins University
2023-2024
University of Iowa
2023
Cancer Genetics (United States)
2021
Oklahoma State University Oklahoma City
2019
The University of Texas at Austin
2016
Cornell University
2011-2014
Appropriate DNA double-strand break (DSB) repair factor choice is essential for ensuring accurate outcome and genomic integrity. The factors that regulate this process remain poorly understood. Here, we identify two repressive chromatin components, the macrohistone variant macroH2A1 H3K9 methyltransferase tumor suppressor PRDM2, which together direct between antagonistic DSB mediators BRCA1 53BP1. macroH2A1/PRDM2 module mediates an unexpected shift from accessible to condensed requires...
Genetic or pharmacological alteration of the activity histone deacetylase 6 (HDAC6) induces a parallel in cell migration. Using tubacin to block deacetylation alpha-tubulin, and not other HDAC6 substrates, yielded motility reduction equivalent agents that all NAD-independent HDACs. Accordingly, we investigated how failure deacetylate tubulin contributes decreased HDAC6-inhibited cells. Testing hypothesis is reduced because cellular adhesion altered, found inhibiting towards rapidly increased...
Abstract Metastasis is the primary cause of treatment failures and mortality in most cancers. Triple-negative breast cancer (TNBC) refractory to rapidly progresses disseminated disease. We utilized an orthotopic mouse model that molecularly phenotypically resembles human TNBC study effects exogenous, daily tissue inhibitor metalloproteinase-2 (TIMP-2) on tumor growth metastasis. Our results demonstrated TIMP-2 maximally suppressed by ~36–50% pulmonary metastasis >92%. Immunostaining...
Totipotent cells have the ability to generate embryonic and extra-embryonic tissues. Interestingly, a rare population of with totipotent-like potential, known as 2 cell (2C)-like cells, has been identified within ESC cultures. They arise from display similar features those found in 2C embryo. However, molecular determinants 2C-like conversion not completely elucidated. Here, we show that CCCTC-binding factor (CTCF) is barrier for reprogramming. Indeed, forced state by transcription DUX...
DNA double-strand breaks (DSBs) and their repair can cause extensive epigenetic changes. As a result, DSBs have been proposed to promote transcriptional and, ultimately, physiological dysfunction via both cell-intrinsic cell-non-autonomous pathways. Studying the consequences of in higher organisms has, however, hindered by scarcity tools for controlled DSB induction. Here, we describe mouse model that allows tissue-specific temporally formation at ∼140 defined genomic loci. Using this model,...
Tumor growth relies on efficient DNA repair to mitigate the detrimental impact of damage associated with excessive cell division. Modulating factor function, thus, provides a promising strategy manipulate malignant growth. Here, we identify ubiquitin-specific protease USP21 as positive regulator BRCA2, key mediator by homologous recombination. interacts with, deubiquitinates and stabilizes BRCA2 promote RAD51 loading at double-strand breaks. As result, depletion decreases recombination...
Abstract Mechanical signals from the extracellular microenvironment have been implicated in tumor and metastatic progression. Here, we identify nucleoporin NUP210 as a metastasis susceptibility gene for human estrogen receptor positive (ER+) breast cancer cellular mechanosensor. Nup210 depletion suppresses lung mouse models of cancer. Mechanistically, interacts with LINC complex protein SUN2 which connects nucleus to cytoskeleton. In addition, NUP210/SUN2 chromatin via short isoform BRD4...
Abstract Cancer stem cells (CSCs) are key drivers of metastasis and therapy resistance but have been challenging to visualize study in situ . Using a fluorescent CSC reporter, we observed very different population dynamics for CSCs nonCSCs during metastatic lung colonization breast cancer models. expansive self-renewal drives early lesion formation before switching maintenance mode balanced differentiation, whereupon nonCSC proliferation takes over as the main driver expansion. Mechanistic...
Allosteric inhibitors of the tyrosine phosphatase SHP2 hold therapeutic promise in cancers with overactive RAS/ERK signaling but "adaptive resistance" to may limit benefits. Here, we utilized tumor cells that proliferate similarly or without endogenous explore means overcome this growth-independence from SHP2. We found depletion profoundly alters output vascular regulators, cytokines, chemokines, and other factors growth-resistant cancer cells. Tumors derived inoculation SHP2-depleted,...
<p>Morphological changes in TRPM4-KO and chronic exposure (CE) cells.</p>
<p>TRPM4 RNA expression and categories of gene sets enriched in response to Acetalax treatment.</p>
<p>Legends for the Supplementary figures.</p>
<p>Scatter plot of Acetalax activity versus TRPM4 transcript expression.</p>
<p>Bisacodyl structure, effect on TNBC cell lines and similarity to Acetalax.</p>
<p>Exogenous TRPM4 expression sensitizes negative and acetalax-resistant MDAMB231 MDAMB436 cells to acetalax.</p>
<p>Mitochondrial morphological changes caused by Acetalax in BT549.</p>
Abstract Acetylation of protein and RNA represent a critical event for development cancer progression. NAT10 is the only known acetylase that catalyzes N4-actylcytidine (ac4C) modification RNAs. Here, we show loss significantly decreases lung metastasis in allograft genetically engineered mouse models breast cancer. interacts with mechanosensitive, susceptibility complex at nuclear pore. In addition to its canonical role acetylation, find p300 gene enhancers. associated mislocalization into...
Glioblastoma-associated macrophages and microglia (GAMs) are the predominant immune cells in tumor microenvironment. Activation of MerTK, a receptor tyrosine kinase, polarizes GAMs to an immunosuppressive phenotype, promoting growth. Here, role MerTK inhibition glioblastoma microenvironment is investigated vitro vivo.Effects MRX-2843 regulation were determined by cell viability, cytokine array, tube formation, Western blotting, wound healing assays. A syngeneic GL261 orthotopic mouse model...
Abstract Purpose: Breast cancer diagnosed in young patients is often aggressive. Because primary breast tumors from and older have similar mutational patterns, we hypothesized that the host microenvironment promotes more aggressive metastatic disease. Experimental Design: Triple-negative or luminal B cell lines were injected into mice side-by-side to quantify lung, liver, brain metastases. Young mouse brains, naïve, analyzed by flow cytometry. Immune populations depleted using antibodies a...