- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Metabolism, Diabetes, and Cancer
- Hemoglobinopathies and Related Disorders
- Nuclear Structure and Function
- Pancreatic function and diabetes
- Genetics, Aging, and Longevity in Model Organisms
- Chronic Myeloid Leukemia Treatments
- Cellular transport and secretion
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Carcinogens and Genotoxicity Assessment
- interferon and immune responses
- Pluripotent Stem Cells Research
- Polysaccharides and Plant Cell Walls
University of North Carolina at Charlotte
2014-2025
Durham University
2014-2023
Woodward (United States)
2015
University of Warwick
2010
Dartmouth College
2001-2009
Columbia University
1992-2008
Cancer Genetics (United States)
2004-2008
Dartmouth–Hitchcock Medical Center
2006-2007
Memorial Sloan Kettering Cancer Center
1996-2005
Cornell University
1998-2004
To directly determine whether recombinational repair of double-strand breaks (DSBs) can occur between heterologous chromosomes and lead to chromosomal rearrangements in mammalian cells, we employed an ES cell system analyze recombination repeats on chromosomes. We found that is induced at least 1000-fold following the introduction a DSB one repeat. Most (98%) recombinants repaired by gene conversion which small amount sequence information was transferred from unbroken chromosome onto broken...
Abstract Background: The mammalian target of rapamycin (mTOR) regulates multiple cellular functions including translation in response to nutrients, especially amino acids. AMP‐activated protein kinase (AMPK) modulates metabolism energy demand by responding changes AMP. Results: treatment SV40‐immortalized human corneal epithelial cells (HCE‐T cells) with 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR), widely used as an AMPK activator, inhibits p70 S6k activities. Altered glucose...
Mammalian cells are able to repair chromosomal double-strand breaks (DSBs) both by homologous recombination and mechanisms that require little or no homology.Although spontaneous is rare, DSBs will stimulate 2 3 orders of magnitude when homology provided either from exogenous DNA in gene-targeting experiments a repeated sequence.Using assay mouse embryonic stem cells, we now investigate the effect heterology on recombinational DSBs.Cells were cotransfected with an endonuclease expression...
The AMP-activated protein kinase (AMPK) is a ubiquitous mammalian important in the adaptation of cells to metabolic stress. enzyme heterotrimer, consisting catalytic α subunit and regulatory β γ subunits, each which member larger isoform family. allosterically regulated by AMP phosphorylation subunit. post-translationally modified myristoylation multi-site phosphorylation. In present study, we have examined impact post-translational modification β-1 on activity, heterotrimer assembly...
DNA double-strand breaks (DSBs) may be caused by normal metabolic processes or exogenous damaging agents and can promote chromosomal rearrangements, including translocations, deletions, chromosome loss. In mammalian cells, both homologous recombination nonhomologous end joining (NHEJ) are important DSB repair pathways for the maintenance of genomic stability. Using a mouse embryonic stem cell system, we previously demonstrated that in one repaired with sequence on heterologous chromosome,...
The human multiple drug resistance (MDR) gene has been used as a selectable marker to increase the proportion of bone marrow cells that contain and express this by selection. By constructing retroviral vectors containing expressing MDR nonselectable such beta-globin gene, enrichment for both these genes can be achieved. A construct cDNA in Harvey virus-based vector transfect our ecotropic 3T3 packaging line GP+E86. Clones have isolated exposure retrovirally transfected (MDR producer cells)...
Abstract The Arabidopsis EH proteins (AtEH1/Pan1 and AtEH2/Pan1) are components of the endocytic TPLATE complex (TPC) which is essential for endocytosis. Both homologues yeast ARP2/3 activator, Pan1p. Here, we show that these also involved in actin cytoskeleton regulated autophagy. AtEH/Pan1 localise to plasma membrane autophagosomes. Upon induction autophagy, recruit TPC AP-2 subunits, clathrin, Increased expression boosts autophagosome formation, suggesting independent redundant pathways...
The endoplasmic reticulum (ER) is connected to the plasma membrane (PM) through plant-specific NETWORKED protein, NET3C, and phylogenetically conserved vesicle-associated protein-associated proteins (VAPs). Ten VAP homologues (VAP27-1 27-10) can be identified in Arabidopsis genome divided into three clades. Representative members from each clade were tagged with fluorescent protein expressed Nicotiana benthamiana. Proteins clades I III localized ER as well ER/PM contact sites (EPCSs),...
Adenovirus-induced hyperleptinemia causes rapid disappearance of body fat in normal rats, presumably by up-regulating fatty acid oxidation within white adipocytes. To determine the role peroxisomal proliferation-activated receptor (PPAR)α expression, which was increased during loss fat, we infused adenovirus–leptin into PPARα −/− and +/+ mice. Despite similar degrees reduction food intake, epididymal pad weight declined 55% wild-type but only 6% mice; liver triacylglycerol fell 39% group...
The AMP-activated protein kinase (AMPK) is a ubiquitous mammalian important in the adaptation of cells to metabolic stress. enzyme heterotrimer, consisting catalytic α subunit and regulatory β γ subunits, each which member larger isoform family. allosterically regulated by AMP phosphorylation subunit. post-translationally modified myristoylation multi-site phosphorylation. In present study, we have examined impact post-translational modification β-1 on activity, heterotrimer assembly...
C75, a synthetic inhibitor of fatty acid synthase (FAS), is hypothesized to alter the metabolism neurons in hypothalamus that regulate feeding behavior contribute decreased food intake and profound weight loss seen with C75 treatment. In present study, we characterize suitability primary cultures cortical for studies designed investigate consequences treatment alteration neurons. We demonstrate neurons, inhibits FAS activity stimulates carnitine palmitoyltransferase-1 (CPT-1), consistent its...
The nuclear envelope contains >100 transmembrane proteins that continuously exchange with the endoplasmic reticulum and move within membranes. To better understand organization dynamics of this system, we compared trafficking 15 integral using FRAP. A surprising 30-fold range mobilities was observed. dynamic behavior several these also analyzed after depletion ATP and/or Ran, two functions implicated in reticulum-inner membrane translocation. This revealed ATP- Ran-dependent translocation...
The SCAR/WAVE complex is required for ARP2/3-mediated actin nucleation, and these complexes are highly conserved in plants animals [1Davidson A.J. Insall R.H. Actin-based motility: WAVE regulatory structure reopens old SCARs.Curr. Biol. 2011; 21: R66-R68Abstract Full Text PDF PubMed Scopus (19) Google Scholar, 2Deeks M.J. Hussey P.J. Arp2/3 SCAR: move to the fore.Nat. Rev. Mol. Cell 2005; 6: 954-964Crossref (58) Scholar]. Proteins from have been found be membrane associated [3Dyachok J. Shao...
Abstract DNA single-strand breaks (SSBs) represent the most abundant type of damage. Unrepaired SSBs impair replication and transcription, leading to cancer neurodegenerative disorders. Although PARP1 XRCC1 are implicated in SSB repair pathway, it remains unclear how signaling pathways coordinated regulated. Using Xenopus egg extract vitro reconstitution systems, here we show that first sensed by APE1 initiate 3′–5′ end resection, followed APE2 recruitment continue resection. Notably, APE1’s...
Objective To explore the factors that influence young men's access to health services with a view identifying potential for promotion interventions in this area. Design A qualitative study using semi-structured interview schedule small groups of men. Setting Interviews were carried out field within school and youth settings. Method series three focus group interviews used as means gathering data. Results It was found participants consistently equated physical fitness, help-seeking behaviour...