A5027876809- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- HIV/AIDS drug development and treatment
- Molecular Biology Techniques and Applications
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Metabolomics and Mass Spectrometry Studies
- Cancer therapeutics and mechanisms
- RNA modifications and cancer
- T-cell and Retrovirus Studies
- Bioinformatics and Genomic Networks
- Drug Transport and Resistance Mechanisms
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
John Brown University
2022-2025
Brown University
2023-2024
USA Mitchell Cancer Institute
2015-2024
University of South Alabama
2015-2024
Massachusetts Institute of Technology
2023-2024
Technical University of Denmark
2023-2024
Willow Wood (United States)
2023
UPMC Hillman Cancer Center
2009-2021
University of Pittsburgh
2010-2021
Leiden University Medical Center
2015
Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in stem cells (GSCs) individual HGG poorly characterized. Here we identified and characterized two mutually exclusive GSC with distinct dysregulated pathways. Analysis mRNA profiles distinguished proneural (PN) from mesenchymal (Mes) GSCs revealed a pronounced correlation the corresponding PN or Mes HGGs. displayed more aggressive...
ARTD1 (PARP1) is a key enzyme involved in DNA repair through the synthesis of poly(ADP-ribose) (PAR) response to strand breaks, and it plays an important role cell death following excessive damage. ARTD1-induced associated with NAD(+) depletion ATP loss; however, molecular mechanism ARTD1-mediated energy collapse remains elusive. Using real-time metabolic measurements, we compared effects activation direct depletion. We found that PAR synthesis, but not depletion, resulted block glycolysis...
Abstract Differential microRNA (miR) expression is described in non–small cell lung carcinoma. miR biogenesis requires a set of proteins collectively referred to as the machinery. In proposed multistep carcinogenesis model, peripheral adenocarcinoma develops from noninvasive precursor lesions known atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). The gene array analysis BAC showed transient up-regulation Dicer (a key effector protein for small interfering RNA...
Abstract DNA-alkylating agents have a central role in the curative therapy of many human tumors; yet, resistance to these limits their effectiveness. The efficacy alkylating agent temozolomide has been attributed induction O6-MeG, DNA lesion repaired by protein O6-methylguanine-DNA methyltransferase (MGMT). Resistance ascribed elevated levels MGMT and/or reduced mismatch repair. However, >80% lesions induced are N-methylated bases that recognized glycosylases and not MGMT, so may also...
Mammalian cells possess two distinct pathways for completion of base excision repair (BER): the DNA polymerase β (Pol β)-dependent short-patch pathway (replacement one nucleotide), which is main route, and long-patch (resynthesis 2−6 nucleotides), PCNA-dependent. To address issue how these share their role in BER ability Pol β-defective mammalian cell extracts to a single abasic site constructed circular duplex plasmid molecule was tested standard vitro reaction. β-deficient were able...
Repair of apurinic/apyrimidinic (AP) sites by mammalian cell extracts was compared using circular and linear DNA substrates. Extracts prepared from polymerase beta (polbeta)-proficient mouse fibroblasts repaired AP on both DNA. However, the isogenic polbeta-knockout cells but not efficiently The circularity-dependent repair extract completely inhibited anti-proliferating nuclear antigen (PCNA) antibody fully restored addition purified PCNA. Pretreatment with endonuclease did improve repair,...
Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM essential to achieve cure. The transcription factor FOXM1 has recently gained attention as master regulator mitotic progression cancer various organs. Here, we demonstrate forms protein complex with the kinase MELK GSCs, leading phosphorylation and activation kinase-dependent manner. This MELK-dependent results subsequent increase regulatory...
The RNase III endonuclease Dicer plays a key role in generation of microRNAs (miRs). We hypothesized that regulates cancer cell susceptibility to immune surveillance through miR processing. Indeed, disruption up-regulated intercellular adhesion molecule (ICAM)-1 and enhanced the tumor cells antigen-specific lysis by cytotoxic T-lymphocytes (CTLs), while expression other immunoregulatory proteins examined was not affected. Blockade ICAM-1 inhibited specific CTLs against Dicer-disrupted cells,...
O6-methylguanine-DNA methyltransferase (MGMT) functions to counteract the cytotoxic effects of alkylating agents, such as nitrosoureas, which play a central role in treatment childhood malignant gliomas. Epigenetic silencing MGMT has been associated with prolonged survival adults gliomas, although association between expression status and outcome pediatric gliomas not defined.We examined duration using tumor samples from Children's Cancer Group 945 study, largest randomized trial for...
Abstract Autophagy is an evolutionarily conserved stress response mechanism that often occurs in apoptosis-defective cancer cells and can protect against cell death. In this study, we investigated how apoptosis autophagy affect each other to chemotherapeutic treatment. We found specific ablation of the proapoptotic function cytochrome c, a key regulator mitochondria-mediated apoptosis, enhanced following Induction required Beclin 1 was associated with blockage cleavage by caspase 8 at two...
Abstract Glioblastoma multiforme (GBM) is a devastating brain tumor with poor prognosis and low median survival time. Standard treatment includes radiation chemotherapy the DNA alkylating agent temozolomide (TMZ). However, large percentage of tumors are resistant to cytotoxic effects TMZ-induced lesion O6-methylguanine due elevated expression repair protein O6-methylguanine-DNA methyltransferase (MGMT) or defect in mismatch (MMR) pathway. Although majority lesions (N7-methylguanine...
We have detected DNA polymerase beta (Polβ), known as a key nuclear base excision repair (BER) protein, in mitochondrial protein extracts derived from mammalian tissue and cells. Manipulation of the N-terminal sequence affected amount Polβ mitochondria. Using fragments, mitochondrion-specific partners were identified, with interactors functioning mainly maintenance import. Of particular interest was identification proteins TWINKLE, SSBP1, TFAM, all which are effectors to function nucleoid....
Abstract Methods for quantifying DNA damage, as well repair of that in a high-throughput format are lacking. Single cell gel electrophoresis (SCGE; comet assay) is widely-used method due to its technical simplicity and sensitivity, but the standard assay has limitations reproducibility throughput. We have advanced SCGE by creating 96-well hardware platform coupled with dedicated data processing software (CometChip Platform). Based on original cometchip approach, CometChip Platform increases...