A5003165520- Cervical Cancer and HPV Research
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- Autophagy in Disease and Therapy
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- DNA Repair Mechanisms
- Head and Neck Cancer Studies
- interferon and immune responses
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- NF-κB Signaling Pathways
- RNA modifications and cancer
- Telomeres, Telomerase, and Senescence
- Oral Health Pathology and Treatment
- Genital Health and Disease
- Ubiquitin and proteasome pathways
- Immune Response and Inflammation
- Cancer, Hypoxia, and Metabolism
- Chromatin Remodeling and Cancer
- Genetic factors in colorectal cancer
- Adenosine and Purinergic Signaling
- Sirtuins and Resveratrol in Medicine
- Cancer Genomics and Diagnostics
- Fibroblast Growth Factor Research
Virginia Commonwealth University
2015-2024
VCU Massey Comprehensive Cancer Center
2021-2024
Virginia Cancer Institute
2011-2024
Philips (Finland)
2019-2021
University of Richmond
2012
Center for Drug Evaluation and Research
2012
Université de Montréal
2012
Lawrence Berkeley National Laboratory
2012
Centre Hospitalier de l’Université de Montréal
2012
In MCF-7 breast tumor cells, ionizing radiation promoted autophagy that was cytoprotective; pharmacological or genetic interference with induced by resulted in growth suppression and/or cell killing (primarily apoptosis). The hormonally active form of vitamin D, 1,25D3, also irradiated sensitized the cells to and suppressed proliferative recovery occurs after alone. 1,25D3 enhanced radiosensitivity overexpress Her-2/neu as well p53 mutant Hs578t cells. contrast, failed alter promote BT474...
Exposure of MCF-7 breast tumor cells or HCT-116 colon carcinoma to clinically relevant concentrations doxorubicin (Adriamycin; Farmitalia Research Laboratories, Milan, Italy) camptothecin results in both autophagy and senescence. To determine whether is required for chemotherapy-induced senescence, reactive oxygen generation induced by Adriamycin was suppressed <i>N</i>-acetyl cysteine glutathione, the induction ataxia telangiectasia mutated, p53, p21 modulated pharmacologically and/or...
Fewer than half of children with high-risk neuroblastoma survive. Many these tumors harbor high-level amplification MYCN, which correlates poor disease outcome. Using data from our large drug screen we predicted, and subsequently demonstrated, that MYCN-amplified neuroblastomas are sensitive to the BCL-2 inhibitor ABT-199. This sensitivity occurs in part through low anti-apoptotic BCL-xL expression, high pro-apoptotic NOXA paradoxical, MYCN-driven upregulation NOXA. Screening for enhancers...
Recognition of the cytoprotective functions autophagy that occur in tumor cells exposed to various forms chemotherapy or radiation has generated intense interest possibility pharmacological interference with could provide a clinical strategy for overcoming therapeutic resistance. Multiple trials are currently progress evaluate antimalarial agent chloroquine (generally its formulation as hydroxychloroquine) and impact on cancer therapy. In this commentary/review, we focus relatively limited...
ABSTRACT To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with origin of replication, can also regulate transcription from adjacent promoters. interacts host in order to both replication; TopBP1 Brd4 are cellular that interact HPV16 E2. Previous work mutants demonstrated requirement for transactivation properties E2, while is required replication induced by association E1. More-recent studies have implicated regulation Here, we...
Human papillomaviruses are pathogens that cause a host of diseases ranging from benign warts to cancers. There no therapeutics available for combating these directly target viral proteins or processes; therefore, we must enhance our understanding HPV life cycles assist with identifying novel treatments.
Human papillomaviruses (HPVs) are causative agents in ano-genital and oropharyngeal cancers. The virus must reprogram host gene expression to promote infection, E6 E7 contribute this via the targeting of cellular transcription factors, including p53 pRb, respectively. HPV16 E2 protein regulates U2OS cells, study, we extend these observations into telomerase reverse transcriptase (TERT) immortalized oral keratinocytes (NOKs) that capable supporting late stages life cycle. We observed...
Human papillomaviruses (HPV) are causative agents in 5% of all cancers, including the majority anogenital and oropharyngeal cancers. Downregulation innate immune genes (IIGs) by HPV to promote viral life cycle is well documented; E6 E7 known repressors these genes. More recently, we demonstrated that E2 could also repress IIGs. These studies have been carried out cells overexpressing proteins, further investigate role individual proteins this repression, introduced stop codons into and/or...
ABSTRACT An interaction between human papillomavirus 16 (HPV16) E2 and the cellular proteins TopBP1 BRD4 is required for plasmid segregation function. The E2-TopBP1 promotes increased mitotic protein levels in U2OS N/Tert-1 cells, as well foreskin keratinocytes immortalized by HPV16 (HFK + HPV16). SIRT1 deacetylation reduces stability here we demonstrate that acetylation occurs during mitosis a interacting-dependent manner, promoting stabilization. p300 mediates due to switching off function...
// Michael R. Evans 1 , Claire D. James Oonagh Loughran Tara J. Nulton Xu Wang Molly L. Bristol Brad Windle 1,2 and Iain M. Morgan Department of Oral Craniofacial Molecular Biology, VCU Philips Institute for Health Research, Virginia Commonwealth University School Dentistry, Richmond, VA, USA 2 Massey Cancer Center, Correspondence to: Morgan, email: Keywords : head neck cancer, human papillomavirus, life-cycle, the cancer genome atlas, keratinocytes Received May 07, 2017 Accepted 17,...
HPV16 is the major viral human carcinogen responsible for between 3 and 4% of all cancers worldwide. Following infection, this virus activates DNA damage response (DDR) to promote its life cycle recruits DDR proteins replicating in order facilitate homologous recombination during replication. This promotes production viable progeny. Our understanding how replication interacts with remains incomplete. Here, we demonstrate that cellular deacetylase SIRT1, which a part E1-E2 complex, regulates...
Human papillomaviruses (HPV) are causative agents in ano-genital and oral cancers; HPV16 is the most prevalent type detected human cancers. The E6 protein targets p53 for proteasomal degradation to facilitate proliferation of infected cell. However, immortalized cells predominantly spliced (E6*) unable degrade p53. Here, we demonstrate that foreskin keratinocytes by (HFK+HPV16), positive oropharyngeal cancers, retain significant expression In addition, levels increase HPV16+ head neck cancer...
HPVs are causative agents in human cancers and responsible for around of 5% all cancers. A better understanding the viral life cycle keratinocytes will facilitate development novel therapeutics to combat HPV-positive Here, we present a unique keratinocyte model identify host proteins that specifically interact with HPV16. Using this system, report cellular gene, SAMHD1, is regulated by HPV16 at RNA protein levels keratinocytes. Elimination SAMHD1 from these cells using CRISPR/Cas9 editing...
Human papillomaviruses cause around 5% of all human cancers, yet there are no specific antiviral therapeutic approaches available for combatting these cancers. These cancers currently treated with standard chemoradiation therapy (CRT). Specific reagents desperately required, particularly HPV+HNSCC whose incidence is increasing and which diagnostic tools this disease. Using data from The Cancer Genome Atlas (TCGA), we others determined that the estrogen receptor alpha (ERα) overexpressed in...
During the human papillomavirus 16 (HPV16) life cycle, E2 protein interacts with host factors to regulate viral transcription, replication, and genome segregation/retention. Our understanding of partner proteins their roles in functions remains incomplete. Here we demonstrate that CK2 phosphorylation on serine 23 promotes interaction TopBP1
Human papillomavirus 16 (HPV16) E2 is a DNA-binding protein that regulates transcription, replication and potentially, segregation of the HPV16 genome during viral life cycle. In model, simultaneously binds to host chromatin, acting as bridge ensure genomes reside in daughter nuclei following cell division. The chromatin receptor for mediating this function unknown. Recently, we demonstrated CK2 phosphorylation on serine 23 (S23) required interaction with TopBP1, promotes TopBP1 recruitment...
Human papillomaviruses (HPVs) are causative agents in almost all cervical carcinomas. HPVs also head and neck cancer, the cases of which increasing rapidly. Viral replication activates DNA damage response (DDR) pathway; associated proteins recruited to foci, this pathway may serve allow for viral genome amplification. Likewise, HPV double-strand breaks (DSBs) could be produced during lead linearization integration. Many studies have shown that integration into host results unregulated...
<b><i>Objectives:</i></b> Mice overexpressing SIRT6 live longer than wild-type mice while knockout exhibit similar degenerative phenotypes as individuals with Hutchinson-Gilford progeria syndrome (HGPS). Thus, we sought to test whether levels of are reduced in cells from HGPS and restored expression may impede premature aging phenotypes. <b><i>Methods:</i></b> Levels endogenous progerin normal fibroblasts were assessed by Western blotting...
Human papillomaviruses (HPVs) are causative agents in around 5% of all cancers, including cervical and oropharyngeal. A feature HPV cancers is their better clinical outcome compared with non-HPV anatomical counterparts. In turn, the presence E2 predicts a HPV-positive cancers; reason(s) for E2-positive patients not fully understood. Previously, we demonstrated that HPV16 regulates host gene transcription relevant to life cycle N/Tert-1 cells. One genes repressed by entire genome cells...