A5008542202- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Cancer Research and Treatments
- Mesenchymal stem cell research
- Genomics and Chromatin Dynamics
- Telomeres, Telomerase, and Senescence
- Muscle Physiology and Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
- Microfluidic and Bio-sensing Technologies
- Phagocytosis and Immune Regulation
- Breast Cancer Treatment Studies
- Tissue Engineering and Regenerative Medicine
- MicroRNA in disease regulation
- Nutrition, Genetics, and Disease
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Skin and Cellular Biology Research
- BRCA gene mutations in cancer
- Cancer, Hypoxia, and Metabolism
- Frailty in Older Adults
City of Hope
2017-2025
Beckman Research Institute
2017-2025
University of Bergen
2017-2025
City Of Hope National Medical Center
2017-2025
Lawrence Berkeley National Laboratory
2014-2023
Berkeley College
2014-2017
Shandong University
2013
Qilu Hospital of Shandong University
2013
Oregon Health & Science University
2013
École Polytechnique Fédérale de Lausanne
2012
Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts zones containing progenitor cells lobules. Putative residing were essentially quiescent, whereas the lobules more likely be actively dividing. Cells from collected under microscope functionally characterized by colony formation on tissue culture plastic, mammosphere suspension culture, morphogenesis...
Fas is a surface receptor that can transmit signals for apoptosis. Using retroviral cDNA library–based functional cloning we identified gene toso, blocks Fas-mediated Toso expression was confined to lymphoid cells and enhanced after cell-specific activation processes in T cells. appeared limited inhibition of apoptosis mediated by members the TNF family capable inhibiting cell self-killing induced TCR up-regulate ligand. We mapped effect caspase-8 processing, most upstream caspase activity...
The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not evaluated. Here, we show that is elevated breast cancer as well ovarian, gastric, colorectal tumors which expression level correlates positively with distant metastasis. overexpression normal or malignant human mammary epithelial cells increased their neoplastic properties vitro vivo, markedly increasing epithelial-mesenchymal transition (EMT) the metastatic capacity...
In adult tissues, multi-potent progenitor cells are some of the most primitive members developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests fate decisions directed by interactions with extrinsic soluble factors, ECM, other cells, as well physical properties ECM. To understand regulation decisions, therefore, would require a means understanding carefully choreographed combinatorial interactions. Here we used...
Stiffness is a biophysical property of the extracellular matrix that modulates cellular functions, including proliferation, invasion, and differentiation, it also may affect therapeutic responses. Therapeutic durability in cancer treatments remains problem for both chemotherapies pathway-targeted drugs, but reasons this are not well understood. Tumor progression accompanied by changes properties tissue, we asked whether rigidity modulated sensitive versus resistant states HER2-amplified...
Significance Differences in cell–cell interfacial energies can explain how multiple cell types sort into spatially organized tissues. However, this strategy of self-organization is not robust to heterogeneity or changes the that drive correct positioning. Therefore, heterogeneous epithelial tissues such as human mammary and prostate glands use a different strategy. First, disorganized aggregates form an adhesive interface at tissue–ECM boundary provides geometric constraints...
Abstract During aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally expressed myoepithelial cells. We hypothesize that loss of is a general manifestation epithelia are susceptible to cancer initiation. In present study, we show histologically normal breast tissue from younger women who cancer, as result harboring germline mutation BRCA1 , BRCA2 or PALB2 genes, exhibits hallmarks accelerated aging. These include proportionately...
Abstract The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) its heterodimer partner ITGB5 β5) as essential α/β pair expansion. High-density gene tiling further pinpointed integral pocket within β-propeller domain αVβ5...
Adult bone marrow-derived cells can participate in muscle regeneration after marrow transplantation. In recent studies a single hematopoietic stem cell (HSC) was shown to give rise that not only reconstituted all of the lineages blood, but also contributed mature fibers. However, relevant HSC derivative with this potential has yet been definitively identified. Here we use fluorescence-activated sorter-based protocols test distinct fractions and show containing c-kit(+) immature...
Abstract Women older than 50 years account for 75% of new breast cancer diagnoses, and the majority these tumors are a luminal subtype. Although age-associated changes, including endocrine profiles alterations within microenvironment, increase risk, an understanding cellular molecular mechanisms that underlies observations is lacking. In this study, we generated large collection normal human mammary epithelial cell strains from women ages 16 to 91 years, derived primary tissues, investigate...
Telomerase reactivation and immortalization are critical for human carcinoma progression. However, little is known about the mechanisms controlling this crucial step, due in part to paucity of experimentally tractable model systems that can examine epithelial cell as it might occur vivo. We achieved efficient non-clonal normal mammary cells (HMEC) by directly targeting 2 main senescence barriers encountered cultured HMEC. The stress-associated stasis barrier was bypassed using shRNA p16INK4;...
Experimental examination of normal human mammary epithelial cell (HMEC) behavior, and how cells acquire abnormal properties, can be facilitated by in vitro culture systems that more accurately model vivo biology. The use derived material for studying cellular differentiation, aging, senescence, immortalization is particularly advantageous given the many significant molecular differences these properties between commonly utilized rodent cells1-2. Mammary present a convenient system because...
The mechanical properties of cells change with their differentiation, chronological age, and malignant progression. Consequently, these may be useful label-free biomarkers various functional or clinically relevant cell states. Here, we demonstrate mechano-node-pore sensing (mechano-NPS), a multi-parametric single-cell-analysis method that utilizes four-terminal measurement the current across microfluidic channel to quantify simultaneously diameter, resistance compressive deformation,...
Aging is associated with tissue-level changes in cellular composition that are correlated increased susceptibility to disease. human mammary tissue shows skewed progenitor cell potency, resulting diminished tumor-suppressive types and the accumulation of defective epithelial progenitors. Quantitative characterization these age-emergent subpopulations lacking, impeding our understanding relationship between age cancer susceptibility. We conducted single-cell resolution proteomic phenotyping...