A5091314004- Prostate Cancer Treatment and Research
- Cancer Cells and Metastasis
- Prostate Cancer Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Cancer, Lipids, and Metabolism
- T-cell and B-cell Immunology
- Xenotransplantation and immune response
- Tissue Engineering and Regenerative Medicine
- FOXO transcription factor regulation
- Gene Regulatory Network Analysis
- Oropharyngeal Anatomy and Pathologies
- Sexual function and dysfunction studies
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Historical, Literary, and Cultural Studies
- 3D Printing in Biomedical Research
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- RNA Research and Splicing
- Hippo pathway signaling and YAP/TAZ
- Cancer Research and Treatments
- Reproductive System and Pregnancy
- Epigenetics and DNA Methylation
University of California, Los Angeles
2015-2024
Broad Center
2015-2024
University of Chicago
2019-2022
UCLA Jonsson Comprehensive Cancer Center
2012-2022
Institute of Molecular Biology
2008-2020
University of Colorado Denver
2012-2019
University of Colorado Cancer Center
2012-2019
Stony Brook University
2017
UCLA Health
2015
Thomas Jefferson National Accelerator Facility
2014
Luminal cells are believed to be the of origin for human prostate cancer, because disease is characterized by luminal cell expansion and absence basal cells. Yet functional studies addressing cancer have not previously been reported a lack relevant in vivo models. Here we show that from primary benign tissue can initiate immunodeficient mice. The cooperative effects AKT, ERG, androgen receptor recapitulated histological molecular features with loss expressing prostate-specific antigen...
The epithelium of the adult prostate contains 3 distinct cell types: basal, luminal, and neuroendocrine. Tissue-regenerative activity has been identified predominantly from basal cells, isolated by expression CD49f stem antigen-1 (Sca-1). An important question for field is whether all cells have characteristics. Prostate-specific microarray databases were interrogated to find candidate surface antigens that could subfractionate population. Tumor-associated calcium signal transducer 2...
Chromosomal rearrangements involving erythroblast transformation specific (ETS) family transcription factors were recently defined as the most common genetic alterations in human prostate cancer. Despite their prevalence, it is unclear what quantitative role they play either initiation or progression of disease. Using a lentiviral transduction and dissociated cell regeneration approach, we find that acutely increased expression ETS proteins adult murine epithelial cells sufficient to induce...
Dominant mutations or DNA amplification of tyrosine kinases are rare among the oncogenic alterations implicated in prostate cancer. We demonstrate that castration-resistant cancer (CRPC) men exhibits increased phosphorylation, raising question whether enhanced kinase activity is observed absence specific mutation amplification. generated a mouse model progression using commonly perturbed non-tyrosine oncogenes and pathways detected significant up-regulation phosphorylation at carcinoma...
The relationship between the cells that initiate cancer and stem-like propagate tumors has been poorly defined. In a human prostate tissue transformation model, basal expressing oncogenes Myc myristoylated AKT can heterogeneous tumors. Tumors contain features of acinar-type adenocarcinoma with elevated eIF4E-driven protein translation squamous cell carcinoma marked by activated beta-catenin. Lentiviral integration site analysis revealed alternative histological phenotypes be clonally derived...
Abstract BACKGROUND Prostate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these have therapeutic implications. Cells from dissociated tissues that form spheres vitro often represent cells. A subset human prostate prostaspheres were evaluated self‐renewal tissue regeneration capability the present study. METHODS Prostaspheres generated 59 prostatectomy specimens. Lineage marker expression TMPRSS‐ERG...
The cell surface protein Trop2 is expressed on immature stem/progenitor-like cells and overexpressed in many epithelial cancers. However the biological function of tissue maintenance tumorigenesis remains unclear. In this study, we demonstrate that a regulator self-renewal, proliferation, transformation. controls these processes through mechanism regulated intramembrane proteolysis leads to cleavage Trop2, creating two products: extracellular domain intracellular domain. released from...
New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties pathways of cell sub-populations capable sustaining the net growth cancer. One best enrichment schemes isolating putative stem/progenitor from murine gland is Lin-;Sca1+;CD49fhi (LSChi), which results in a more than 10-fold vitro sphere-forming activity. We have shown previously that LSChi subpopulation both necessary sufficient initiation Pten-null model. To further improve this...
Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that are poorly understood. Here, we demonstrate low expression of CD38 identifies progenitor-like subset luminal cells in human prostate. CD38lo enriched glands adjacent to inflammatory and exhibit epithelial nuclear κB (NF-κB) signaling. In response oncogenic transformation, can initiate cancer an vivo tissue-regeneration assay. Finally, phenotype gene signature associated with disease...
Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting AR+ luminal tumor cells and AR- neuroendocrine (NE) cells, may contribute failure. Here, we describe the successful purification NE from primary fresh human adenocarcinoma based on cell surface C-X-C motif chemokine 2 (CXCR2). Functional studies revealed CXCR2 be a driver phenotype, including...
Aging is associated with loss of tissue mass and a decline in adult stem cell function many tissues. In contrast, aging the prostate growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, effects on epithelial cells have not been established. Here we find that organoid-forming progenitor activity mouse basal luminal maintained age. This caused by an age-related expansion progenitor-like share features human cells. The increase may contribute to greater risk for...
Abstract Lineage transitions are a central feature of prostate development, tumourigenesis and treatment resistance. While epigenetic changes well known to drive lineage transitions, it remains unclear how upstream metabolic signalling contributes the regulation epithelial identity. To fill this gap, we developed an approach perform metabolomics on primary cells. Using approach, discovered that basal luminal cells exhibit distinct metabolomes nutrient utilization patterns. Furthermore,...
Significance A high nuclear Notch homolog 1, translocation-associated (Notch1) intracellular domain level distinguishes high-risk prostate cancer and castration-resistant from benign low/intermediate-risk cancer. Chronic activation of Notch1 cooperates with multiple oncogenic pathways altered in early cancer, including AKT, Myc, Ras/Raf/MAPK, to promote progression androgen ablation-resistant adenocarcinoma.
Epithelial-specific activation of the PI3-kinase pathway is most common genetic alteration in type I endometrial cancer. In majority these tumors, PTEN expression lost epithelium but maintained tumor stroma. Currently reported knockout mouse models initiate cancer concomitant with loss both uterine and Consequently, biologic outcome selectively activating remains unknown. To address this question, we established a malleable vivo regeneration system from dissociated murine Regenerated glands...
Computers are organized into hardware and software. Using a theoretical approach to identify patterns in gene expression variety of species, organs, cell types, we found that biological systems similarly comprised relatively unchanging hardware-like pattern. Orthogonal software-like transcripts vary greatly, even among tumors the same type from different individuals. Two distinguishable classes could be identified within component: those highly expressed stable an adaptable subset with lower...
Synchronous with massive shifts in reproductive hormones, the uterus and its lining endometrium expand to accommodate a growing fetus during pregnancy. In absence of an embryo endometrium, composed epithelium stroma, undergoes numerous hormonally regulated cycles breakdown regeneration. The mediated regenerative capacity suggests that signals govern growth endometrial progenitors must be by estrogen progesterone. Here, we report antigenic profile for isolation mouse epithelial progenitors....
Background. Recombinant T-cell receptor ligand 1000 (RTL1000) is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG-) 35-55 peptide. Analogues RTL1000 induce tolerance, reverse clinical and histological disease, promote repair in experimental autoimmune encephalomyelitis (EAE) DR2 transgenic, C57BL/6, SJL/J mice. Objective. Determining maximum tolerated dose, safety, tolerability multiple sclerosis (MS) subjects....
Despite several recent studies addressing the cells of origin for prostate cancer, there is still considerable discussion in field regarding most relevant target populations transformation. Tissue regeneration have pointed to a basal cell mouse and human cancer. In contrast, genetically engineered models demonstrate that within both luminal layers can initiate murine Based on differences between these two approaches, we propose further work should address requirement microenvironmental...
Cancer cell metabolism requires sustained pools of intracellular nicotinamide adenine dinucleotide (NAD+) which is maintained by a balance NAD+ hydrolase activity and salvage activity. We recently reported that human prostate cancer can be initiated following oncogene expression in progenitor-like luminal cells marked low the NAD+-consuming enzyme CD38. CD38 reduced compared to benign prostate, suggesting tumor may reduce order enhance NAD+. However, little known about how repressed advanced...