A5048856695- DNA Repair Mechanisms
- Metal complexes synthesis and properties
- PARP inhibition in cancer therapy
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- Trace Elements in Health
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Esophageal Cancer Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Cancer-related gene regulation
- Polyamine Metabolism and Applications
- Endoplasmic Reticulum Stress and Disease
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- Prostate Cancer Treatment and Research
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
The Ohio State University
2018-2025
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2019-2024
Nanjing Medical University
2024
Nanjing Tech University
2023
The Ohio State University Wexner Medical Center
2020-2023
Linyi People's Hospital
2020-2021
Case Western Reserve University
2011-2018
Sichuan University
2010-2017
West China Hospital of Sichuan University
2010-2016
University Hospitals Seidman Cancer Center
2016
The amino acid antiporter system Xc- is important for the synthesis of glutathione (GSH) that functions to prevent lipid peroxidation and protect cells from nonapoptotic, iron-dependent death (i.e., ferroptosis). While activity often positively correlates with expression level its light chain encoded by SLC7A11, inhibition small molecules (e.g., erastin) causes a decrease in intracellular GSH level, leading ferroptotic cell death. How regulated during ferroptosis remains largely unknown....
The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. A growing body evidence suggests that promotion DNA double-strand break repair by homologous recombination (HR) may be means maintains genomic stability, while a role in error-prone nonhomologous (NHR) processes has just begun to elucidated. protein becomes phosphorylated response damage, but effects phosphorylation on recombinational are unknown. In...
Objective: Suicide is a major social and public health problem, but its neurobiology in depressive disorder poorly understood. The purpose of this study was to use magnetic resonance diffusion tensor imaging characterize abnormalities white matter integrity patients with without history suicide attempts. Method: Participants were 52 disorder, (N=16) (N=36) attempts, healthy comparison subjects matched for age, gender, education, ethnicity. Diffusion 3.0 Tesla scanner performed. Whole-brain...
A-type lamins are emerging as regulators of nuclear organization and function. Changes in their expression associated with cancer mutations linked to degenerative diseases -laminopathies-. Although a correlation exists between alterations genomic instability, the molecular mechanisms remain largely unknown. We previously found that loss leads degradation 53BP1 protein defective long-range non-homologous end-joining (NHEJ) dysfunctional telomeres. Here, we determined how affects repair...
The serine synthesis pathway (SSP) involving metabolic enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphatase (PSPH) drives intracellular biosynthesis is indispensable for cancer cells to grow in serine-limiting environments. However, how SSP regulated not well understood. Here, we report that activating transcription factor 3 (ATF3) crucial transcriptional activation of upon deprivation. ATF3 rapidly induced by deprivation via a mechanism...
The protein products of several rad checkpoint genes Schizosaccharomyces pombe (rad1+, rad3 +, rad9 rad17 rad26 and hus1 +) play crucial roles in sensing changes DNA structure, function the maintenance telomeres. When mammalian homologue S. Rad9 was inactivated, increases chromosome end-to-end associations frequency telomere loss were observed. This instability correlated with enhanced S- G2-phase-specific cell killing, delayed kinetics γ-H2AX focus appearance disappearance, reduced...
Abstract The tumor suppressor gene BRCA1 maintains genomic integrity by protecting cells from the deleterious effects of DNA double-strand breaks (DSBs). Through its interactions with checkpoint kinase 2 (Chk2) and Rad51, promotes homologous recombination, which is typically an error-free repair process. In addition, accumulating evidence implicates in regulation nonhomologous end-joining (NHEJ), may involve precise religation DSB ends if they are compatible (i.e., repair) or sequence...
The function of BRCA1 and BRCA2 in DNA repair could affect the sensitivity cells to cytotoxic agents, would therefore be an important component planning therapy for breast ovarian cancers. Previously, both BRCA1- BRCA2-deficient tumors were shown sensitive mitomycin C, mechanism was presumed a defect interstrand crosslinks by homologous recombination. Here, we show that determine drug, etoposide, using genetic complementation BRCA-deficient cells. Etoposide is known bind topoisomerase II...
mTOR (mammalian target of rapamycin) signaling plays a key role in the development many tumor types. Therefore, is an attractive for cancer therapeutics. Although inhibitors are thought to have radiosensitization activity, molecular bases remain largely unknown. Here we show that treating MCF7 breast cells with rapamycin (an inhibitor) results significant suppression homologous recombination (HR) and nonhomologous end joining (NHEJ), two major mechanisms required repairing ionizing...
Failure to reactivate stalled or collapsed DNA replication forks is a potential source of genomic instability. Homologous recombination (HR) major mechanism for repairing the damage resulting from arrest. The single-strand (ssDNA)-binding protein, protein A (RPA), plays role in multiple processes metabolism. However, RPA2 hyperphosphorylation, which occurs response damage, had been unclear. Here, we show that hyperphosphorylated associates with ssDNA and recombinase Rad51 arrest by...
Loss of 53BP1 rescues BRCA1 deficiency and is associated with BRCA1-deficient triple-negative breast cancers (TNBC) resistance to genotoxic drugs. The mechanisms responsible for decreased transcript protein levels in tumors remain unknown. Here, we demonstrate that loss activates cathepsin L (CTSL)-mediated degradation 53BP1. Activation this pathway rescued homologous recombination repair allowed cells bypass growth arrest. Importantly, depletion or inhibition CTSL vitamin D specific...
The solute carrier family 13 member 5 (SLC13A5) is a sodium-coupled transporter that mediates cellular uptake of citrate, which plays important roles in the synthesis fatty acids and cholesterol. Recently, pregnane X receptor (PXR, NR1I2), initially characterized as xenobiotic sensor, has been functionally linked to regulation various physiologic processes are associated with lipid metabolism energy homeostasis. Here, we show <i>SLC13A5</i> gene novel transcriptional target PXR, altered...
Abstract Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are approved to treat recurrent ovarian cancer with BRCA1 or BRCA2 mutations, and as maintenance therapy for platinum-sensitive (BRCA wild-type mutated) after treatment platinum. However, the acquired resistance against PARPi remains a clinical hurdle. Here, we demonstrated that PARP inhibitor (olaparib)–resistant epithelial (EOC) cells exhibited an elevated aldehyde dehydrogenase (ALDH) activity, mainly contributed by increased...
Abstract Over 50% of all patients with cancer are treated radiotherapy. However, radiotherapy is often insufficient as a monotherapy and requires nontoxic radiosensitizer. Squalene epoxidase (SQLE) controls cholesterol biosynthesis by converting squalene to 2,3-oxidosqualene. Given that SQLE frequently overexpressed in human cancer, this study investigated the importance breast non–small cell lung (NSCLC), two cancers SQLE-positive IHC staining was observed 68% 56% NSCLC specimens versus 15%...
Electro-responsive dynamic hydrogels, which possess robust mechanical properties and precise spatiotemporal resolution, have a wide range of applications in biomedicine energy science. However, it is still challenging to design prepare electro-responsive hydrogels (ERHs) all these properties. Here, we report one such class ERHs with features, based on the direct current voltage (DCV)-induced rearrangement sodium dodecyl sulfate (SDS) micelles, where can tune hydrogel networks that are...
The O -GlcNAc transferase (OGT) is an essential enzyme that mediates protein -GlcNAcylation, a unique form of posttranslational modification many nuclear and cytosolic proteins. Recent studies observed increased OGT -GlcNAcylation levels in broad range human cancer tissues compared to adjacent normal tissues, indicating universal effect promoting tumorigenesis. Here, we show for tumor growth immunocompetent mice by repressing the cyclic GMP-AMP synthase (cGAS)-dependent DNA sensing pathway....
The insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that organize signaling complexes downstream of activated cell surface receptors. Here, we show IRS-1 and IRS-2, despite significant homology, play critical yet distinct functions in breast cancer, identify specific pathways influenced by using the polyoma virus middle-T (PyV-MT) transgenic mouse model mammary carcinoma Irs-1 null (Irs1−/−) mice. absence expression enhanced metastatic spread significantly without a effect...
Abstract Alternative non-homologous end joining (alt-NHEJ) was originally identified as a backup repair mechanism in the absence of classical NHEJ (c-NHEJ) factors but recent studies have demonstrated that alt-NHEJ is active even when c-NHEJ well homologous recombination available. The functions 53BP1 processes are not understood. Here, we report promotes DNA double-strand break (DSB) and genomic stability only c-NHEJ-proficient also -deficient human G1-phase cells. Using an array substrates...