A5018176450- DNA Repair Mechanisms
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- Cancer, Lipids, and Metabolism
- Chromosomal and Genetic Variations
- Ultrasound and Hyperthermia Applications
- Photoacoustic and Ultrasonic Imaging
- RNA Research and Splicing
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Histone Deacetylase Inhibitors Research
- Glutathione Transferases and Polymorphisms
- 14-3-3 protein interactions
- Hedgehog Signaling Pathway Studies
- Nuclear Structure and Function
- Medicinal Plant Pharmacodynamics Research
- Cytomegalovirus and herpesvirus research
- Cancer Cells and Metastasis
City Of Hope National Medical Center
2018-2019
City of Hope
2018
Beckman Research Institute
2018
University of Virginia
2014-2016
Virginia Tech
2009-2016
Many cancer cells display a CIN (Chromosome Instability) phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, number different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes CIN. However, comprehensive theory how is perpetuated still lacking. We used colorectal model system to investigate possible cellular mechanism(s) underlying found that...
Spindle assembly, establishment of kinetochore attachment, and sister chromatid separation must occur during mitosis in a highly coordinated fashion to ensure accurate chromosome segregation. In most vertebrate cells, the nuclear envelope break down allow interaction between microtubules mitotic spindle kinetochores. It was previously shown that breakdown (NEB) is not with centrosome can be either complete at time NEB or completed after NEB. this study, we investigated whether timing affects...
The mitotic spindle self-assembles in prometaphase by a combination of centrosomal pathway, which dynamically unstable microtubules search space until chromosomes are captured, and chromosomal grow from focus to the poles. Quantitative mechanistic understanding how assembly can be both fast accurate is lacking. Specifically, it unclear how, if at all, chromosome movements combining pathways affect speed accuracy. We used computer simulations high-resolution microscopy test plausible...
The Mis18 complex specifies the site of new CENP-A nucleosome assembly by recruiting CENP-A-specific factor HJURP (Holliday junction recognition protein). human consists Mis18α, Mis18β, and binding protein 1 (Mis18BP1/hsKNL2). Although Mis18α Mis18β are highly homologous proteins, we find that their conserved YIPPEE domains mediate distinct interactions essential to link deposition existing centromeres. We directly interacts with N terminus Mis18BP1, whereas CENP-C during G1 phase, revealing...
In the last decade, it has become clear that epigenetic changes act together with genetic mutations to promote virtually every stage of tumorigenesis and cancer progression. This knowledge triggered searches for "epigenetic drugs" can be developed into new therapies. Here we report triptolide reduced lung incidence from 70% 10% in a Fen1 E160D transgenic mouse model effectively inhibited growth metastasis A549 H460 xenografts. We found induced cell apoptosis was associated global histone 3...
Abstract Loss of monoubiquitination histone H2B (H2Bub1) was found to be associated with poor-differentiation and enhanced malignancy lung adenocarcinoma. This study investigated the association impact ubiquitin-specific peptidase 22 (USP22), an H2Bub1 deubiquitinase, on stem cell-like characteristics cisplatin resistance in cancer-initiating cells (CIC) from primary CICs were isolated, enriched, characterized patient-derived cancer tissues using both vitro tumorsphere formation vivo...
Homologous recombination (HR) is a highly conserved pathway that can facilitate the repair of DNA double-strand breaks (DSB). Several Deubiquitinases (DUB) have been implicated as key players in damage (DDR) through HR. Here, we report USP22, DUB overexpressed multiple cancer types, necessary for HR direct interaction with PALB2 its C-terminal WD40 domain. This stimulates USP22 catalytic activity vitro. Furthermore, show BRCA2, PALB2, and Rad51 recruitment to DSBs this is, part, stabilizing...
The 1.7 kb DRAIC long noncoding RNA inhibits tumor growth, cancer cell invasion, migration, colony formation and interacts with IKK (IkB kinase) subunits, inhibiting the phosphorylation degradation of NF-kB inhibitor, IkB, to suppress activation NF-kB. Whether these activities are all linked is unclear. We used SHAPE-MaP obtain secondary structure lncRNA perform structure-functions studies which identified minimal region necessary for repressing A 36-nucleotide hairpin (A+B) within NF-kB,...
<p>Knockdown of USP22 in A549, H1299, and H838 lung cancer cells significantly down-regulated ALDH1A3 mRNA expression these cells</p>
<p>Immunofluorescence of CD133 and USP22/H2Bub1</p>
<p>USP22 knockdown with another USP22-shRNA</p>
<p>Correlation between the levels of CD133 (PROM1) mRNA with that ALDH1A3 in lung adenocarcinoma tissues from TCGA portal</p>
<p>Correlation between the levels of USP22 mRNA with that ALDH1A3 in lung Adenocarcinoma tissues from TCGA portal</p>
<p>Supplemental Figure Legend</p>
<div>Abstract<p>Loss of monoubiquitination histone H2B (H2Bub1) was found to be associated with poor-differentiation and enhanced malignancy lung adenocarcinoma. This study investigated the association impact ubiquitin-specific peptidase 22 (USP22), an H2Bub1 deubiquitinase, on stem cell-like characteristics cisplatin resistance in cancer-initiating cells (CIC) from primary CICs were isolated, enriched, characterized patient-derived cancer tissues using both <i>in...
<p>Supplementary Figure 1</p>
<p>USP22 knockdown with another USP22-shRNA</p>
<p>Knockdown of USP22 in A549, H1299, and H838 lung cancer cells significantly down-regulated ALDH1A3 mRNA expression these cells</p>
<p>Correlation between the levels of USP22 mRNA with that ALDH1A3 in lung Adenocarcinoma tissues from TCGA portal</p>
<p>Correlation between the levels of CD133 (PROM1) mRNA with that ALDH1A3 in lung adenocarcinoma tissues from TCGA portal</p>
<p>Immunofluorescence of CD133 and USP22/H2Bub1</p>