A5027688474- Cervical Cancer and HPV Research
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Chemokine receptors and signaling
- interferon and immune responses
- Bacteriophages and microbial interactions
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- HIV Research and Treatment
- T-cell and Retrovirus Studies
- Viral-associated cancers and disorders
- Influenza Virus Research Studies
- Autophagy in Disease and Therapy
- Animal Disease Management and Epidemiology
- Epigenetics and DNA Methylation
- HIV/AIDS drug development and treatment
- Viral gastroenteritis research and epidemiology
- Head and Neck Cancer Studies
Michigan State University
2019-2025
Michigan United
2020-2023
University of Colorado Denver
2011-2020
University of Colorado Anschutz Medical Campus
2018
Color (United States)
2017
University of Wisconsin–Madison
1996-2011
Center for Cancer Research
2007
Institute of Virology of the Slovak Academy of Sciences
2007
Howard Hughes Medical Institute
2005
Abstract Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), other cancers. Because HNCs also arise in HPV-negative patients, this type cancer provides unique opportunities define similarities differences HPV-positive versus arising the same tissue. Here, we describe genome-wide expression profiling 84 HNCs, site-matched normal epithelial samples which used laser capture microdissection enrich for tumor-derived cells. This...
Human papillomaviruses (HPVs) are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, as vaccines and microbicides, to prevent HPV infections. Developing the latter requires better understanding of infectious life cycle HPVs. The closely linked differentiation state stratified epithelium it infects, progeny virus only made terminally differentiating suprabasal compartment. It has long been recognized that must first establish its...
Significance Cervical cancer (CxCa) is the second most frequent in women and third leading cause of death worldwide. Our global analysis gene expression normal, precancerous, cancerous cervical tissue shows increased DNA replication/repair cell proliferation followed by substantial metabolic shifts. We observed a dramatic, progressive decrease estrogen receptor alpha (ERα) tumor progression, ranking specimens estrogen-responsive correlated remarkably with histopathology. Whereas ERα shuts...
ABSTRACT Human papillomaviruses (HPVs) are small DNA viruses causally associated with benign warts and multiple cancers, including cervical head-and-neck cancers. While the vast majority of people exposed to HPV, most instances infection cleared naturally. However, intrinsic host defense mechanisms that block early establishment HPV infections remain mysterious. Several antiviral cytidine deaminases human APOBEC3 (hA3) family have been identified as potent viral mutators. editing genomes in...
High-risk human papillomaviruses (HPVs) are causally associated with multiple cancers. Previous studies have shown that the HPV oncoprotein E7 induces immune suppression; however, underlying mechanisms remain unknown. To understand by which deregulates host responses in tumor microenvironment, we analyzed gene expression changes of all known chemokines and their receptors using our global data sets from HPV-positive -negative head/neck cancer cervical tissue specimens different disease...
Papillomaviruses are small DNA viruses that associated with benign and malignant epithelial lesions, including >95% of cervical cancers ≈20% head neck cancers. Because papillomavirus replication virion production tied to cell differentiation, infectious has been limited cumbersome organotypic cultures mouse xenografts. Consequent difficulties in obtaining useful amounts wild-type or mutant human (HPV) virions have greatly studies on many aspects biology. To overcome these limitations, we...
Nuclear factor-kappa B (NFκB) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in pathogenesis inflammatory and infectious diseases. Mice with genetic disruption p50 subunit are more likely to succumb Mycobacterium tuberculosis (MTB). However, role defense humans not fully understood. We sought examine activation immune response human macrophages MTB. Targeted...
Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 3 can block entry of a broad spectrum RNA viruses. However, no study date focused on role IFITM in DNA virus restriction. Here, we demonstrate IFN-α or -β treatment keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, expression....
More than 270 different types of papillomaviruses have been discovered in a wide array animal species. Despite the great diversity papillomaviruses, little is known about evolutionary processes that drive host tropism and emergence oncogenic genotypes. Although defense mechanisms evolved to interfere with various aspects virus life cycle, viruses also coevolved copious strategies avoid antiviral restriction. Our other studies shown cytidine deaminase APOBEC3 family members edit HPV genomes...
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 APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer genomes, including those cervical and head neck cancers caused by papillomavirus (HPV) infection. However, the driving forces that promote off-target A3 activity remain mostly unclear. Here, we report mechanism for dramatic increase A3A protein levels HPV-positive keratinocytes. We show expression viral E7 from high-risk HPVs, but not low-risk significantly prolongs cellular half-life keratinocytes cell...
Abstract Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression antitumor immune responses. To investigate extent gene expression dysregulated by E7-induced DNA methylation, we analyzed parallel global using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, NIKS-16∆E7. show MHC class I genes is...
Evasion of the host immune responses is critical for both persistent human papillomavirus (HPV) infection and associated cancer progression. We have previously shown that expression homeostatic chemokine CXCL14 significantly downregulated by HPV oncoprotein E7 during Restoration in HPV-positive head neck (HNC) cells dramatically suppresses tumor growth increases survival through an immune-dependent mechanism mice. Although recruits natural killer (NK) T to microenvironment, which mediates...
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...
There is great enthusiasm toward the development of novel immunotherapies for treatment cancer, and given their roles in immune system regulation, chemokines stand out as promising candidates use new cancer therapies. Many previous studies have shown how chemokine signaling pathways could be targeted to halt progression. We others revealed that CXCL14 promotes antitumor responses, suggesting may effective immunotherapy. However, it still unknown what mechanism governs CXCL14-mediated...
The natural vibrational frequencies of biological particles such as viruses and bacteria encode critical information about their mechanical states they interact with local environment undergo structural evolution. However, detecting tracking these vibrations within a context at the single particle level has remained elusive. In this study, we track motions single, unlabeled virus under ambient conditions using ultrafast spectroscopy. ultrasonic spectrum an 80 to 100 nm lentiviral pseudovirus...
Interleukin-10 (IL-10), produced by Th2 helper T cells, B and macrophages, can inhibit cytokine production Th1 cells enhance B-cell proliferation differentiation. Here, we show that peripheral blood mononuclear (PBMCs) from bovine leukemia virus-infected animals with late-stage disease express considerably more IL-10 mRNA than are not infected or in the early stages of disease. In contrast, quantities type 1 cytokines, IL-2 gamma interferon, decrease progression. addition, observed is...
ABSTRACT Prostaglandin E 2 (PGE ), produced by macrophages, has important immune regulatory functions, suppressing a type 1 response and stimulating response. Type cytokines (interleukin-2 [IL-2], IL-12, gamma interferon) increase in freshly isolated peripheral blood mononuclear cells (PBMCs) of animals with an early disease stage bovine leukemia virus (BLV) infection, while IL-10 increases late stage. Although immunosuppressive role the host system, also inhibits BLV tax pol mRNA levels...