A5066439030- Gene Regulatory Network Analysis
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Genomics, phytochemicals, and oxidative stress
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Molecular Communication and Nanonetworks
- Advanced biosensing and bioanalysis techniques
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
University of Minnesota
2020-2025
University of Minnesota System
2020-2023
Twin Cities Orthopedics
2023
University of Minnesota Medical Center
2020-2022
Sonalysts (United States)
2021
Center for Cancer Research
2012-2020
Institute of Cell Biology and Neurobiology
2020
National Institutes of Health
2011-2019
National Cancer Institute
2011-2019
Cancer Institute (WIA)
2017
Cells transmit information through molecular signals that often show complex dynamical patterns. The dynamic behavior of the tumor suppressor p53 varies depending on stimulus; in response to double-strand DNA breaks, it shows a series repeated pulses. Using computational model, we identified sequence precisely timed drug additions alter pulses instead produce sustained response. This leads expression different set downstream genes and also alters cell fate: experience recover from damage,...
The EnvZ/OmpR system in Escherichia coli , which regulates the expression of porins OmpF and OmpC, is one simplest best-characterized examples two-component signaling. Like many other histidine kinases, EnvZ bifunctional; it phosphorylates dephosphorylates response regulator OmpR. We have analyzed a mathematical model EnvZ-mediated cycle OmpR phosphorylation dephosphorylation. predicts that when much less abundant than OmpR, as case E. steady-state level phosphorylated (OmpR-P) insensitive...
We performed transposon mutagenesis of a two-color fluorescent reporter strain to identify new regulators the porin genes ompF and ompC in Escherichia coli. Screening colonies by fluorescence microscopy revealed numerous mutants that exhibited interesting patterns expression. One mutant harbored an insertion gene encoding histidine kinase CpxA, sensor for two-component signaling system responds envelope stress. The cpxA increased transcription very strong decrease under conditions which...
A key circuit in the response of cells to damage is p53-mdm2 feedback loop. This shows sustained, noisy oscillations individual human following DNA breaks. Here, we apply an engineering approach known as systems identification quantify vivo interactions on basis accurate measurements its power spectrum. We obtained oscillation time courses p53 and Mdm2 protein levels from several hundred analyzed their Fourier spectra. find characteristic spectra with distinct low-frequency components that...
Abstract Understanding the mechanisms supporting tumor-initiating cells (TIC) is vital to combat advanced-stage recurrent cancers. Here, we show that in advanced ovarian cancers NFκB signaling via RelB transcription factor supports TIC populations by directly regulating cancer stem-like associated enzyme aldehyde dehydrogenase (ALDH). Loss of significantly inhibited spheroid formation, ALDH expression and activity, chemoresistance, tumorigenesis subcutaneous intrabursal mouse xenograft...
CRISPR/Cas9 is a powerful gene editing tool for knockout studies and functional genomic screens. Successful implementation of CRISPR often requires Cas9 to elicit efficient target in population cells. In this study, we investigated the role several key factors, including variation copy number, inherent potency sgRNA guides, expression level sgRNA, determining efficiency. Using isogenic, clonal cell lines with variable numbers an EGFP transgene, discovered that relatively insensitive but...
Supraphysiological MYC levels are oncogenic. Originally considered a typical transcription factor recruited to E-boxes (CACGTG), another theory posits global amplifier increasing output at all active promoters. Both models rest on large-scale genome-wide ”-omics’. Because the assumptions, statistical parameter and model choice dictates ‘-omic’ results, whether is general or specific remains controversial. Therefore, an orthogonal series of experiments interrogated MYC’s effect expression...
Recent studies have shown that many cell-signaling networks contain interactions and feedback loops give rise to complex dynamics. Synthetic biology has allowed researchers construct analyze well-defined signaling circuits exhibiting behavior can be predicted quantitatively understood. Combining these approaches—wiring natural network components together with engineered interactions—has the potential precisely modulate dynamics of endogenous processes control cell decisions they influence....
Article26 September 2019Open Access Source DataTransparent process p53 pulse modulation differentially regulates target gene promoters to regulate cell fate decisions Marie D Harton Laboratory of Cell Biology, Center for Cancer Research, National Institute, Institutes Health, Bethesda, MD, USA This article has been contributed by US Government employees and their work is in the public domain USA. Search more papers this author Woo Seuk Koh Amie Bunker Abhyudai Singh Department Electrical...
Abstract Oscillatory p53 expression occurs in individual cells responding to DNA breaks. While the majority of exhibit same qualitative response, quantitative features oscillations (e.g., amplitude or period) can be highly variable between cells, generating heterogeneity downstream cell fate responses. Since detrimental therapies based on damage, methods induce synchronization across a population have potential generate more predictable responses DNA-damaging treatments. Using mathematical...
// Diane M. Kambach 1 , Alan S. Halim A. Gesine Cauer Qian Sun Carlos Tristan Orieta Celiku Aparna H. Kesarwala Uma Shankavaram Eric Batchelor 2 Jayne Stommel Radiation Oncology Branch, National Cancer Institute, Institutes of Health, Bethesda, MD 20892, USA Laboratory Pathology, Correspondence to: Stommel, email: jayne.stommel@nih.gov Keywords: cholesterol metabolism, oxygen utilization, glioblastoma, pre-clinical cancer therapies, cell cycle Received: August 10, 2016 Accepted: January 2017...
Summary We have used a fusion of GFP to the response regulator OmpR image spatial distribution in live cells Escherichia coli . observed foci increased OmpR–GFP fluorescence that appear be due interactions with histidine kinase EnvZ. also colocalization clusters plasmids carrying binding sites, which enabled us develop simple method for imaging DNA cells. peak intensity within quantify extent localization either EnvZ or DNA. With these assays we compared effects osmolarity and procaine, both...
Abstract Synthetic biological circuits that can generate outputs with distinct expression dynamics are useful for a variety of biomedical and industrial applications. We present method to control output by altering mRNA decay rates. Using oscillatory the transcription factor p53 as circuit regulator, we use two approaches controlling target gene transcript degradation rates based on gene’s 3′-untranslated region (3′-UTR): introduction copies destabilizing AU-rich elements into 3′-UTR or...
We show that for two well-characterized regulatory circuits in Escherichia coli, Tn10 tetracycline resistance and porin osmoregulation, the transcriptional outputs individual cells are graded functions of applied stimuli. These systems therefore examples naturally occurring exhibit continuous control transcription. Surprisingly, however, we find osmoregulation is open loop; i.e., expression level does not feed back into circuit. This mode particularly interesting an organism such as E. which...
In response to DNA damage, the transcription factor p53 accumulates in a series of pulses. While dynamics play critical role regulating stress responses, how pulsing affects target protein expression is not well understood. Recently, we showed that pulses generate diversity mRNA dynamics; however, given and are necessarily correlated, it remains be determined impact expression. Using computational experimental approaches, show decay rates filter pulses: Distinct generated depending on...