A5065954539- Cervical Cancer and HPV Research
- Cancer-related Molecular Pathways
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Healthcare Systems and Public Health
- Viral-associated cancers and disorders
- Head and Neck Cancer Studies
- Hippo pathway signaling and YAP/TAZ
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- Genital Health and Disease
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Olfactory and Sensory Function Studies
- Biochemical Analysis and Sensing Techniques
- Academic Publishing and Open Access
- Historical and Contemporary Political Dynamics
- SARS-CoV-2 and COVID-19 Research
- Polyomavirus and related diseases
- Animal Disease Management and Epidemiology
- Advanced Chemical Sensor Technologies
- Cancer Genomics and Diagnostics
- Zoonotic diseases and public health
University of Pennsylvania
2017-2024
Oregon Health & Science University
2023
John Wiley & Sons (United States)
2022-2023
Queensland Children’s Hospital
2023
Harvard University
2007-2017
University of Massachusetts Boston
2017
University of Michigan
2013-2017
University of Kansas
1987-2017
University of Waterloo
2017
Western Michigan University
2017
Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those breast, head/neck, cervix, bladder, lung, ovary, other tissues. A3B is upregulated these tumor types relative to normal tissues, but mechanism unclear. Because also has antiviral activity systems member broader response, we tested hypothesis that papillomavirus (HPV) infection causes...
Although multiple studies have documented the expression of over 70 novel virus-encoded microRNAs (miRNAs), targets and functions most these regulatory RNA species are unknown. In this study a comparative bioinformatics approach was employed to identify potential human cytomegalovirus (HCMV) mRNA miRNA miR-UL112-1. Bioinformatics analysis known HCMV 3' untranslated regions (UTRs) revealed 14 viral transcripts that were predicted contain functional target sites for The screened using...
More than 120 human papillomaviruses (HPVs) have now been identified and associated with a variety of clinical lesions. To understand the molecular differences among these viruses that result in lesions distinct pathologies, we begun MS-based proteomic analysis HPV–host cellular protein interactions created plasmid cell line libraries required for studies. validate our system, characterized host proteins bind to E7 expressed from 17 different HPV types. These studies reveal number...
We have begun to define the human papillomavirus (HPV)-associated proteome for a subset of more than 120 HPV types that been identified date. Our approach uses mass spectrometry-based platform systematic identification interactions between and host cellular proteins, here we report proteomic analysis E6 proteins from 16 different types. The viruses included represent high-risk, low-risk, non-cancer-associated genus alpha as well four species in beta. interaction data set consists 153...
An essential step in the pathogenesis of human papillomavirus (HPV)-associated cancers is dysregulated expression viral oncogenes. The E2 protein can silence long control region (LCR) promoter that controls E6 and E7 oncogene expression. mechanisms by which represses cellular factors through mediates this silencing are largely unknown. We conducted an unbiased, genome-wide siRNA screen series secondary screens identified 96 genes contribute to repression HPV LCR. In addition confirming a...
The Notch signaling pathway is a key determinant in keratinocyte differentiation and growth cycle arrest, has been reported to have tumor suppressor function skin. papillomavirus life intricately linked the status of keratinocytes. Papillomaviruses are associated with benign proliferative epithelial lesions their respective hosts. Although human papillomaviruses (HPVs) genital tract extensively studied, studies cutaneous HPVs more limited. In particular, it well established that E6 proteins...
Retinoic acid-inducible gene I (RIG-I) is a key pattern recognition receptor that senses viral RNA and interacts with the mitochondrial adaptor MAVS, triggering signaling cascade results in production of type interferons (IFNs). This axis initiated by K63-linked ubiquitination RIG-I mediated E3 ubiquitin ligase TRIM25, which promotes interaction MAVS. USP15 was recently identified as an upstream regulator stabilizing enzyme through removal degradative K48-linked polyubiquitin, ultimately...
Merkel cell carcinoma (MCC) frequently contains integrated copies of polyomavirus DNA that express a truncated form Large T antigen (LT) and an intact Small (ST). While LT binds RB inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show specifically the MYC homolog MYCL (L-MYC) recruits 15-component EP400 histone acetyltransferase chromatin remodeling complex. We performed large-scale immunoprecipitation for identified...
ABSTRACT The major transformation activity of the high-risk human papillomaviruses (HPV) is associated with E7 oncoprotein. interaction HPV retinoblastoma family proteins important for several activities; however, this does not fully account E7-specific cellular immortalization and activities. We have determined that non-receptor protein tyrosine phosphatase PTPN14 interacts from many genus alpha beta types. find E7, but low-risk or necessary sufficient to reduce steady-state level in cells....
Significance Human papillomaviruses (HPV) uncouple proliferation from differentiation to enable virus replication in epithelial cells. HPV E7 proteins are well established promote by binding and inactivating retinoblastoma family other cell cycle inhibitors. However, mechanisms which high-risk oncoproteins inhibit have not been defined. This paper identifies a mechanism keratinocyte differentiation. The inhibition of requires degradation the cellular protein PTPN14 E7, this is related...
Persistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly 5% cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative at same anatomical site, prompting hypothesis that an HPV-encoded protein inactivates and activates effector yes-associated (YAP1). The HPV E7 oncoprotein is required for HPV-mediated oncogenic transformation. We investigated effects oncoproteins on YAP1...
ABSTRACT In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology paramount frameworks should be reviewed periodically. Changes made with care, however, to avoid impeding science that essential for rapidly reducing responding pandemic threats as well addressing more common challenges caused by infectious diseases. Decades uniquely positioned US able respond COVID-19 crisis astounding speed, delivering life-saving vaccines...
Proteomic identification of human papillomavirus type 16 (HPV16) E6-interacting proteins revealed several involved in ubiquitin-mediated proteolysis. In addition to the well-characterized E6AP ubiquitin-protein ligase, a second HECT domain protein (HERC2) and deubiquitylating enzyme (USP15) were identified by tandem affinity purification HPV16 E6-associated proteins. This study focuses on functional consequences interaction E6 with USP15. Overexpression USP15 resulted increased levels...
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...
Caveolae, flask shaped invaginations of the cell membrane, influence signalling cascades in many types. We have tested hypothesis that caveolae modulate excitation-contraction coupling (ECC) and beta-adrenergic stimulation adult cardiac myocyte.Shortening, [Ca(2+)](i) L-type Ca(2+) current (I(Ca,L)) were recorded rat ventricular myocytes. Caveolae disrupted with methyl-beta-cyclodextrin (MbetaC).Shortening transient amplitude reduced myocytes treated MbetaC. MbetaC did not alter density or...
The human cytomegalovirus (HCMV) IE2 86-kDa protein is a key viral transactivator and an important regulator of HCMV infections. We used the genome cloned as bacterial artificial chromosome (BAC) to construct four mutants with disruptions in regions 86 that are predicted be for its transactivation autoregulatory functions. Three these have mutations remove amino acids 356 359, 427 435, 505 511, which disrupts region implicated activation early promoters, zinc finger domain, putative...
The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly patients with genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two HPV E6 proteins bind and/or increase steady-state levels p53 squamous epithelial cells. This is contrast a well-characterized ability cancer-associated HPVs alpha HPV, which inactivate by targeting its...