A5001889895- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Head and Neck Cancer Studies
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Cancer Risks and Factors
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- RNA modifications and cancer
- Hippo pathway signaling and YAP/TAZ
- Molecular Biology Techniques and Applications
- Cervical Cancer and HPV Research
- Cancer-related molecular mechanisms research
- Estrogen and related hormone effects
- Metastasis and carcinoma case studies
- RNA Research and Splicing
- BRCA gene mutations in cancer
- Breast Cancer Treatment Studies
- Developmental Biology and Gene Regulation
- Cell Adhesion Molecules Research
- Pluripotent Stem Cells Research
- HER2/EGFR in Cancer Research
- Telomeres, Telomerase, and Senescence
- Genomics and Chromatin Dynamics
Tufts University
2014-2024
Convergence
2015-2024
Université Libre de Bruxelles
2018
Tufts Medical Center
2007-2016
Molecular Oncology (United States)
2006-2016
Boston University
2006-2016
Institut thématique Génétique, génomique et bioinformatique
2014
Washington University in St. Louis
2013
Duke University
2013
Baylor College of Medicine
2012
Current models of stem cell biology assume that normal and neoplastic cells reside at the apices hierarchies differentiate into nonstem progeny in a unidirectional manner. Here we identify subpopulation basal-like human mammary epithelial departs from assumption, spontaneously dedifferentiating stem-like cells. Moreover, oncogenic transformation enhances spontaneous conversion, so cancer give rise to (CSC)-like vitro vivo. We further show differentiation state cells-of-origin is strong...
Abstract Introduction The phenotypic and functional differences between cells that initiate human breast tumors (cancer stem cells) those comprise the tumor bulk are difficult to study using only primary tissue. We embarked on this hypothesizing cancer cell lines would contain analogous hierarchical differentiation programs found in tumors. Methods Eight (human mammary epithelial cells, MCF10A, MCF7, SUM149, SUM159, SUM1315 MDA.MB.231 were analyzed flow cytometry for CD44, CD24,...
The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary cancer with xenotransplanted human cells have failed to recapitulate the full extent development seen breast. We developed an orthotopic xenograft model which both stromal components reconstructed gland are origin. Genetic modification before implantation ostensibly resulted outgrowth benign malignant lesions. This experimental allows for studies...
Abstract The establishment of metastasis depends on the ability cancer cells to acquire a migratory phenotype combined with their capacity recreate secondary tumor in distant tissue. In epithelial cancers, such as those breast, epithelial-mesenchymal transition (EMT) is associated basal-like breast generates stem-like properties, and enables cell dissemination metastasis. However, molecular mechanism(s) that connects stem cell–like characteristics EMT has yet be defined. Using an orthotopic...
Many tumors contain heterogeneous populations of cells, only some which exhibit increased tumorigenicity and resistance to anticancer therapies. Evidence suggests that these aggressive cancer often termed “cancer stem cells” or stem-like (CSCs), rely upon developmental signaling pathways are important for survival expansion normal cells. Here we report that, in analogy embryonic mammary epithelial biology, estrogen expands the pool functional breast CSCs through a paracrine FGF/FGFR/Tbx3...
Abstract Obesity is one of the most important preventable causes cancer and significant risk factor for breast in postmenopausal women. Compared with lean women, obese women are more likely to be diagnosed a larger, higher grade tumor, an increased incidence lymph node metastases, elevated distant recurrence. However, mechanisms connecting obesity pathogenesis poorly defined. Here, we show that during obesity, adipocytes within human mouse tissues recruit activate macrophages through...
Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the differentiation states of epithelial cells in breast: luminal (EpCAM + ) basal/myoepithelial (CD10 ). However, there also rare types cancers, such as metaplastic carcinomas, where exhibit features alternate cell that no longer resemble epithelium. Until now, it has been difficult identify type(s) human...
Abstract Currently, an in vivo model of human breast cancer metastasizing from the orthotopic site to bone does not exist, making it difficult study many steps skeletal metastasis. Moreover, models used identify mechanisms by which metastasizes are limited intracardiac injection, seeds cells directly into circulation, thus bypassing early metastatic process. Such do reflect full process metastasis occurring patients. We have developed animal and target osteotropic both origin. The engrafted...
Normal and neoplastic breast tissues are comprised of heterogeneous populations epithelial cells exhibiting various degrees maturation differentiation. While cultured cell lines have been derived from both normal malignant tissues, it remains unclear to what extent they retain similar levels differentiation heterogeneity as that found within tissues. We used 12 reduction mammoplasty 15 primary cancer 20 human (16 lines, 4 lines) perform flow cytometry for CD44, CD24, adhesion molecule...
Abstract Numerous hormonal factors contribute to the lifetime risk of breast cancer development. These include inherited genetic mutations, age menarche, menopause, and parity. Inexplicably, there is evidence indicating that ovariectomy prevents formation both estrogen receptor (ER)–positive ER-negative cancers, suggesting cancers are dependent on ovarian hormones for their formation. To examine mechanism(s) by which this may be occurring, we investigated hypothesis steroid promote outgrowth...
Identification of breast cancer stem cells as the within tumors that have ability to give rise make up bulk tumor mass has shifted focus research. However, there is still much debate concerning unique nature markers distinguish in breast. As such, understanding whether CD44+/CD24- are merely more successful overcoming an engraftment incompatibility exists when injecting human into mouse adipose tissue or indeed bona fide great importance.
Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation this process is not well understood. We identified Hippo transducer WWTR1/TAZ a screen transcription factors that are able to prompt lineage switching mammary epithelial cells. Forced expression TAZ luminal induces them adopt basal characteristics, depletion and/or myoepithelial leads differentiation. In human mouse tissues, active only critical for...
Abstract Although BRCA1 function is essential for maintaining genomic integrity in all cell types, it unclear why increased risk of cancer individuals harbouring deleterious mutations restricted to only a select few tissues. Here we show that human mammary epithelial cells (HMECs) from -mutation carriers ( mut/+ ) exhibit instability and rapid telomere erosion the absence tumour-suppressor loss. Furthermore, uncover novel form haploinsufficiency-induced senescence (HIS) specific cells, which...