A5053625755- Cancer-related Molecular Pathways
- Estrogen and related hormone effects
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
- Cytokine Signaling Pathways and Interactions
- Animal Genetics and Reproduction
- Cancer Research and Treatments
- RNA Research and Splicing
- COVID-19 Clinical Research Studies
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Genomics and Chromatin Dynamics
- Cell death mechanisms and regulation
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- NF-κB Signaling Pathways
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- BRCA gene mutations in cancer
- Cancer Risks and Factors
- Long-Term Effects of COVID-19
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
National Institutes of Health
1989-2025
Georgetown University
2015-2024
Technical University of Munich
2023-2024
Institute for Advanced Study
2023-2024
National Institute of Diabetes and Digestive and Kidney Diseases
1997-2024
Georgetown University Medical Center
2013-2023
University of Applied Sciences Kufstein
2020-2021
Krankenhaus Meran
2021
Hospital of the Brothers of St. John of God
2021
Dankook University
2011-2020
Abstract Background Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, characterized mammary tumor gene expression profiles from 13 different murine using DNA microarrays and compared resulting data those tumors. Results Unsupervised hierarchical clustering analysis showed that six (TgWAP- Myc , TgMMTV- Neu PyMT TgWAP- Int3 Tag TgC3(1)- ) yielded...
Promoters whose temporal activity can be directly manipulated in transgenic animals provide a tool for the study of gene functions vivo. We have evaluated tetracycline-responsive binary system its ability to temporally control expression mice. In this system, tetracycline-controlled trans-activator protein (tTA), composed repressor tetracycline-resistance operon (tet from Escherichia coli transposon Tn10) and activating domain viral VP16 herpes simplex virus, induces transcription minimal...
To delete genes specifically from mammary tissue using the Cre- lox system, we have established transgenic mice expressing Cre recombinase under control of WAP gene promoter and MMTV LTR. activity in these was evaluated by three criteria. First, distribution mRNA analyzed. Second, an adenovirus carrying a reporter used to determine expression at level single cells. Third, specificity determined mouse strain gene. In adult MMTV- transgene confined striated ductal cells salivary gland...
Programmed cell death (PCD) of mammary alveolar cells during involution commences within hours the end suckling. Locally, milk accumulates lumens; systemically, levels lactogenic hormones fall. Four experimental models were used to define role local factors as compared with systemic first and second stages involution. In three models, release was disrupted in presence hormones: ( i ) sealing teats, ii gland transplants that cannot due absence a teat connection, iii inactivation oxytocin...
The role of viral oncoprotein expression in the maintenance cellular transformation was examined as a function time through controlled simian virus 40 T antigen (TAg). Expression TAg submandibular gland transgenic mice from birth induced and extensive ductal hyperplasia by 4 months age. reversed when silenced for 3 weeks. When after 7 months, however, persisted even though absent. Although polyploidy cells could be at age, age remained polyploid absence TAg. These results support model...
Molecular expression profiling of tumors initiated by transgenic overexpression c-myc , c-neu c-ha-ras polyoma middle T antigen ( PyMT ) or simian virus 40 T/t (T-ag) targeted to the mouse mammary gland have identified both common and oncogene-specific events associated with tumor formation progression. The shared great similarities in their gene-expression profiles as compared normal an induction cell-cycle regulators, metabolic zinc finger proteins, protein tyrosine phosphatases, along...
Little is known about the embryonic factors that regulate size of primordial follicle endowment at birth. A few studies suggest members B-cell lymphoma/leukemia-2 (bcl-2) family protooncogenes may be important determinants. Thus, purpose this study was to test whether bcl-2 regulates pool To hypothesis, three lines transgenic mice (c-kit/bcl-2 mice) were generated overexpress human in an effort reduce prenatal oocyte loss. The overexpression targeted ovary and appropriate time period with...
Breast tumor suppressor gene 1 (BRCA1) plays an essential role in maintaining genomic integrity. Here we show that mouse Brca1 is required for DNA-damage repair and crossing-over during spermatogenesis. Male Brca1(Delta11/Delta11)p53(+/-) mice carried a homozygous deletion of exon 11 p53 heterozygous mutation had significantly reduced testicular size no spermatozoa their seminiferous tubules. During spermatogenesis, homologous chromosomes from the mutant synapsed advanced to pachytene stage...
Expression of bovine papillomavirus type 1 (BPV-1) late genes is limited to terminally differentiated keratinocytes in an infected epithelium. We have previously shown that although the BPV-1 polyadenylation site functional nonpermissive cells, a 53-nucleotide (nt) fragment 3' untranslated region acts posttranscriptionally reduce polyadenylated cytoplasmic RNA levels. This 53-nt does not appear function by destabilizing (P. A. Furth and C. Baker, J. Virol. 65:5806-5812, 1991). In this study,...
Transcriptional control regions which direct transgene expression to all tissues in transgenic animals can be useful tools for gain-of-function experiments animals. A candidate this purpose is the regulatory region of human cytomegalovirus immediate early 1 gene (HCMVIE1) highly expressed many lines tissue culture cells. Here we analyzed activity HCMVIE1 enhancer/promoter using a sensitive reporter gene, bacterial chloramphenicol acetyltransferase (CAT) gene. Three mice with an intact were...
Abstract Signal transducers and activators of transcription (STATs) are latent cytoplasmic factors that activated translocated into the nucleus after phosphorylation at a conserved tyrosine residue. Mouse model studies have demonstrated Stat5a acts as critical survival factor for normal, preneoplastic malignant mammary epithelial cells. Very limited information is available, however, on expression, status nuclear localization in human breast cancers. In our study, pattern cellular was...
Abstract Molecular mechanisms of development and disease can be studied in transgenic animals. Controlling the spatial temporal expression patterns transgenes, however, is a prerequisite for elucidation gene function whole organism. Previously we reportted that mice carrying tet R/VP16 hybrid (tTA), under control hunman cytomegalovirus immediate early 1 (HCMV‐IE1) promoter, used to temporally activate transgenes promoter containing op sequences. We now show MMTV‐LTR target tTA epthelial...
Abstract The progesterone receptor (PR) plays roles in normal mammary development and breast cancer formation, where it may exert both stimulatory inhibitory actions. Previously, the susceptibility gene product BRCA1 was found to interact with inhibit transcriptional activity of estrogen receptor-α. In this study, we that exogenous wild-type inhibited PR transient transfection assays utilizing a mouse tumor virus-Luc reporter. Wild-type endogenous human cells (T47D MCF-7) PR-A, PR-B, [PR-A...
Knowledge about the impact of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elderly on mRNA vaccination response is needed to appropriately address demand for additional vaccinations in this vulnerable population. Here, we show that octogenarians, a high-risk population, mount sustained SARS-CoV-2 spike-specific immunoglobulin G (IgG) antibody 15 months following infection. This boosts levels 35-fold upon receiving single dose BNT162b2 vaccine after recovery...
Antibody response following Omicron infection is reported to be less robust than that other variants. Here we investigated how prior vaccination and/or modulates response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no infection, vaccinated/no unvaccinated/prior vaccinated/prior infection. The percentage patients with asymptomatic or mild disease was highest the group (87%) lowest (47%)....
SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses clinical manifestations in human patients.
Abstract Overexpression of the oncogene amplified in breast cancer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) induces mammary tumorigenesis mice. In cancer, high levels AIB1/SRC-3 and growth factor HER2/neu predict resistance to endocrine therapy poor outcome. However, a mechanistic relationship between development has not been shown. Here, we show that deletion one allele SRC-3 significantly delays Neu-induced tumor Homozygous mice completely prevents formation. By ages 3 4 months,...