A5081013459- Cervical Cancer and HPV Research
- Cancer-related Molecular Pathways
- interferon and immune responses
- Head and Neck Cancer Studies
- RNA modifications and cancer
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- DNA Repair Mechanisms
- NF-κB Signaling Pathways
- Genital Health and Disease
- Ubiquitin and proteasome pathways
- T-cell and Retrovirus Studies
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Cell death mechanisms and regulation
- Immune Response and Inflammation
- Glioma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Oral Health Pathology and Treatment
- Genetic factors in colorectal cancer
- Fibroblast Growth Factor Research
- Hepatitis B Virus Studies
- Chromatin Remodeling and Cancer
- Molecular Biology Techniques and Applications
Virginia Commonwealth University
2004-2024
Philips (Finland)
2019-2021
Children's Hospital of Richmond at VCU
2019
University of Birmingham
2013-2017
Baxter (United States)
2016
Cancer Research UK Clinical Trials Unit
2013
University of California, San Francisco
2012
Neurological Surgery
2011
Nottingham City Hospital
1995
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...
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.
The membrane-associated RING-CH-type finger ubiquitin ligase MARCHF8 is a human homolog of the viral ligases Kaposi’s sarcoma herpesvirus K3 and K5 that promote host immune evasion. Previous studies have shown ubiquitinates several receptors, such as major histocompatibility complex II CD86. While papillomavirus (HPV) does not encode any ligase, oncoproteins E6 E7 are known to regulate ligases. Here, we report expression upregulated in HPV-positive head neck cancer (HNC) patients but...
ABSTRACT The human papillomavirus (HPV) oncoprotein E7 is a relatively short-lived protein required for HPV-driven cancer development and maintenance. degraded through ubiquitination mediated by cullin 1 (CUL1) the ubiquitin-conjugating enzyme E2 L3 (UBE2L3). However, proteins are maintained at high levels in most HPV-positive cells. A previous proteomics study has shown that UBE2L3 CUL1 increased knockdown of E3 ubiquitin ligase membrane-associated ring-CH-type finger 8 (MARCHF8). We have...
ABSTRACT Human papillomavirus (HPV) E6 proteins of high-risk alpha types target a select group PSD95/DLG1/ZO1 (PDZ) domain-containing by using C-terminal PDZ-binding motif (PBM), an interaction that can be negatively regulated phosphorylation the PBM protein kinase A (PKA). Here, we have mutated canonical PKA recognition partially overlaps with in HPV18 genome (E6153PKA) and compared effect this mutation on HPVl8 life cycle primary keratinocytes wild-type second mutant lacks (E6ΔPDZ). Loss...
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...
Abstract Therapeutic innovation for human papilloma virus‐related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is impaired by inadequate preclinical models the absence of accurate biomarkers. Our study establishes first well‐characterized panel patient‐derived xenografts (PDXs) organoids from HPV+ HNSCCs while determining fidelity to distinguishing genetic features this cancer type. Despite low engraftment rates, whole exome sequencing showed that PDXs retain multiple HNSCC lost in...
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...
HPV + oropharyngeal squamous cell carcinoma (OPC) incidence recently surpassed cervical cancer and is the most common HPV-related in developed world. HPV16 ∼90 % of OPCs, with episomal genomes majority cases. Most existing HPV16+ lines derive from outside oropharynx harbor integrated genomes. Thus, there need for OPC preclinical models to evaluate standard experimental therapeutics presence oncogenic drivers. Here we characterize genome structures eight patient-derived xenografts (PDXs),...
We examined the impact of purified bacterially synthesized GST-MDA-7 (IL-24) and ionizing radiation on proliferation survival non-established human glioblastoma multiforme (GBM) cells. Glioma cell types expressing mutated PTEN p53 molecules, activated ERBB1VIII, over-expressing wild type ERBB1 or without receptor over-expression were selected. In MTT assays, caused a dose-dependent reduction in glioma cells; however only at higher concentrations did reduce viability. The anti-proliferative...
// 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 recruit a host of DNA damage response factors to their viral genome facilitate homologous recombination replication in association with the E1 and E2. We previously demonstrated that SIRT1 deacetylation WRN promotes recruitment E1-E2 replicating regulates both levels fidelity replication. The by results an active protein able complex DNA, but is less stable. Here, we demonstrate inverse correlation between CIN cervical lesions compared normal control tissue, supporting...
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...
High-risk (HR) human papillomaviruses are known causative agents in 5% of cancers including cervical, ano-genital and head neck carcinomas. In part, HR-HPV causes cancer by targeting host-cell tumor suppressors retinoblastoma protein (pRb) RB-like proteins p107 p130. E7 uses a LxCxE motif to bind RB proteins, impairing their ability control cell-cycle dependent transcription. disrupts DREAM (Dimerization partner, RB-like, E2F MuvB), transcriptional repressor complex that can include p130 or...
Human papillomavirus 16 (HPV16) is a causative agent in around 3%-4% of all human cancers, and currently, there are no anti-viral therapeutics available for combating this disease burden. In order to identify new therapeutic targets, we must increase our understanding the HPV16 life cycle. Previously, demonstrated that an interaction between E2 cellular protein TopBP1 mediates plasmid segregation function E2, allowing distribution viral genomes into daughter nuclei following cell division....
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...