A5033587895- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Bladder and Urothelial Cancer Treatments
- Cancer, Lipids, and Metabolism
- Cancer-related gene regulation
- Bioinformatics and Genomic Networks
- Cancer Immunotherapy and Biomarkers
- Molecular Biology Techniques and Applications
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Urinary and Genital Oncology Studies
- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- PI3K/AKT/mTOR signaling in cancer
- Immunotherapy and Immune Responses
- Animal Genetics and Reproduction
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Cancer Research and Treatments
- Wnt/β-catenin signaling in development and cancer
- Prostate Cancer Diagnosis and Treatment
- Immune cells in cancer
Columbia University Irving Medical Center
2016-2025
Columbia University
2012-2024
Weatherford College
2023
New York Proton Center
2010-2019
Cancer Genetics (United States)
2014-2018
Johnson University
2000-2013
Memorial Sloan Kettering Cancer Center
2013
Herbert Irving Comprehensive Cancer Center
2007-2013
Sylvester Comprehensive Cancer Center
2013
Center for Systems Biology
2013
In aging men, the prostate gland becomes hyperproliferative and displays a propensity toward carcinoma. Although this process has been proposed to represent an inappropriate reactivation of embryonic differentiation program, regulatory genes responsible for normal development function are largely undefined. Here we show that murine Nkx3.1 homeobox gene is earliest known marker epithelium during embryogenesis subsequently expressed at all stages in vivo as well tissue recombinants. A null...
Changes in the substrate specificities of factors that irreversibly modify histone components chromatin are expected to have a profound effect on gene expression through epigenetics. Ezh2 is histone-lysine methyltransferase with activity dependent its association other Polycomb Repressive Complexes 2 and 3 (PRC2/3). levels increasingly elevated during prostate cancer progression. Other PRC2/3 also cells. Overexpression tissue culture promotes formation previously undescribed PRC complex,...
The AKT/mammalian target of rapamycin (AKT/mTOR) and ERK MAPK signaling pathways have been shown to cooperate in prostate cancer progression the transition androgen-independent disease. We now tested effects combinatorial inhibition these on tumorigenicity by performing preclinical studies using a genetically engineered mouse model cancer. report here that combination therapy rapamycin, an inhibitor mTOR, PD0325901, kinase 1 (MEK; directly upstream ERK), inhibited cell growth cultured lines...
Current treatments for castration-resistant prostate cancer (CRPC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here, we provide novel insights into treatment response the antiandrogen abiraterone by analyses of a genetically engineered mouse (GEM) model with combined inactivation
Although bladder cancer represents a serious health problem worldwide, relevant mouse models for investigating disease progression or therapeutic targets have been lacking. We show that combined deletion of p53 and Pten in epithelium leads to invasive novel model. Inactivation PTEN promotes tumorigenesis human cells is correlated with poor survival tumors. Furthermore, the synergistic effects are mediated by deregulation mammalian target rapamycin (mTOR) signaling, consistent ability block...
We have isolated a prostate-specific gene (NKX3.1) in humans that is homologous to theDrosophilaNK homeobox family. Northern blot analyses indicate this expressed at high levels adult prostate and much lower level testis, but little or not all several other tissues. In an androgen-dependent carcinoma line, LNCaP,NKX3.1mRNA basal was increased markedly upon androgen stimulation; theNKX3.1mRNA undetectable human tumor cell lines including two androgen-independent lines. TheNKX3.1gene maps...
Mouse models have provided significant insights into the molecular mechanisms of tumor suppressor gene function. Here we use mouse prostate carcinogenesis to demonstrate that Nkx3.1 homeobox undergoes epigenetic inactivation through loss protein expression. Loss function in mice cooperates with Pten cancer progression. This cooperativity results synergistic activation Akt (protein kinase B), a key modulator cell growth and survival. Our findings underscore significance interactions between...
Protein-protein interactions are known to be essential for specifying the transcriptional activities of homeoproteins.Here we show that representative members Msx and Dlx homeoprotein families form homoand heterodimeric complexes.We demonstrate dimerization by proteins is mediated through their homeodomains residues required this interaction correspond those necessary DNA binding.Unlike most other examples interactions, association does not promote cooperative binding; instead, binding...
During embryogenesis, differentiation of skeletal muscle is regulated by transcription factors that include members the Msx homeoprotein family. By investigating Msx1 function in repression myogenic gene expression, we identified a physical interaction between and H1b, specific isoform mouse histone H1. We found H1b bind to key regulatory element MyoD, central regulator differentiation, where they induce repressed chromatin. Moreover, cooperate inhibit cell culture Xenopus animal caps. Our...
During development, patterning and morphogenesis of tissues are intimately coordinated through control cellular proliferation differentiation. We describe a mechanism by which vertebrate Msx homeobox genes inhibit differentiation regulation the cell cycle. show that misexpression Msx1 via retroviral gene transfer inhibits multiple mesenchymal epithelial progenitor types in culture. This activity is associated with its ability to upregulate cyclin D1 expression Cdk4 activity, while has...
The EGF-CFC gene Cripto encodes an extracellular protein that has been implicated in the signaling pathway for transforming growth factor beta (TGF) ligand Nodal.Although recent findings frog and fish embryos have suggested proteins function as coreceptors Nodal, studies cell culture a factor-like molecule.Here we reconcile these apparently disparate models of by using mammalian assay to investigate activities Nodal proteins.Using luciferase reporter assay, found consistent with its being...
Significance Although locally invasive prostate cancer is nearly always curable, metastatic usually results in lethality. Our study investigates the temporal progression and molecular mechanisms underlying metastasis using a new genetically engineered mouse model. Using lineage-tracing analyses, we show that dissemination of tumor cells occurs early progression, well before occurrence metastases. We further temporally coincident with expression oncogenic ETS gene Etv4 , promotes vivo....