A5086028278- Cancer-related Molecular Pathways
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Biomedical Ethics and Regulation
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Prostate Cancer Treatment and Research
- Computational Drug Discovery Methods
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- Bioinformatics and Genomic Networks
- Telomeres, Telomerase, and Senescence
- Immunotherapy and Immune Responses
- Xenotransplantation and immune response
- Gut microbiota and health
- Autophagy in Disease and Therapy
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Bladder and Urothelial Cancer Treatments
- CRISPR and Genetic Engineering
- Sirtuins and Resveratrol in Medicine
- Metabolomics and Mass Spectrometry Studies
National Institute of Environmental Health Sciences
2018-2023
Triangle
2023
Duke University
2010-2017
Duke Medical Center
2013-2015
Duke University Hospital
2013
Weizmann Institute of Science
2003-2009
Israel Defense Forces Medical Corps
1999
The tumor suppressor p53 is an important regulator that controls various cellular networks, including cell differentiation. Interestingly, some studies suggest facilitates differentiation, whereas others claim it suppresses Therefore, critical to evaluate whether this inconsistency represents authentic differential activity manifested in the differentiation programs.To clarify issue, we conducted a comparative study of several mesenchymal programs. effects knockdown or enhanced were analyzed...
Methionine restriction, a dietary regimen that protects against metabolic diseases and aging, represses cancer growth improves therapy. However, the response of different cells to this nutritional manipulation is highly variable, molecular determinants heterogeneity remain poorly understood. Here we report hepatocyte nuclear factor 4α (HNF4α) dictates sensitivity liver methionine restriction. We show hepatic sulfur amino acid (SAA) metabolism under transcriptional control HNF4α. Knocking...
Abstract Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts progression the context intact immune system is unknown. Here we report that while inhibiting immunocompromised mice, reduces T cell abundance, exacerbates tumour impairs response immunotherapy immunocompetent male female mice. Mechanistically, microbial production hydrogen...
Inactivation of p53 and activation telomerase occur in the majority human cancers, raising possibility a link between these two pathways. Overexpression wild-type down-regulates enzymatic activity various cancer cell lines through transcriptional repression its catalytic subunit, reverse transcriptase (hTERT). In this study, we re-evaluated role regulation using isogenic expressing physiological levels p53. We demonstrate that endogenous was able to down-regulate activity, hTERT mRNA levels,...
Given the very substantial heterogeneity of most human cancers, it is likely that cancer therapeutics will be active in only a small fraction any population patients. As such, development new therapeutics, coupled with methods to match therapy individual patient, critical achieving significant gains disease outcome. One such opportunity use expression signatures identify key oncogenic phenotypes can serve not as biomarkers but also means identifying therapeutic compounds might specifically...
Quantifying cell-type proportions and their corresponding gene expression profiles in tissue samples would enhance understanding of the contributions individual cell types to physiological states tissue. Current approaches that address heterogeneity have drawbacks. Experimental techniques, such as fluorescence-activated sorting, single RNA sequencing are expensive. Computational use data from heterogeneous promising, but most current methods estimate either or cell-type-specific by requiring...
Abstract Background Human cancer cell line profiling and drug sensitivity studies provide valuable information about the therapeutic potential of drugs their possible mechanisms action. The goal those is to translate findings from in vitro lines into vivo relevance and, eventually, patients’ care. Tremendous progress has been made. Results In this work, we built predictive models for 453 using data on gene expression (IC 50 ) lines. We identified many known drug-gene interactions uncovered...
Abstract Prostate cancer is the most commonly diagnosed type of in men, and there no available cure for patients with advanced disease. In vitro model systems are urgently required to permit study human prostate cell differentiation malignant transformation. Unfortunately, cells particularly difficult convert into continuously growing cultures. We report here successful immortalization without viral oncogenes epithelial and, first time, stromal cells. These exhibit a significant pattern...
The transcription factor E2F1 is a key regulator of proliferation and apoptosis but the molecular mechanisms that mediate these cell fate decisions remain unclear. Here, we identify FOXO factors as target genes act in feed-forward regulatory loop to reinforce gene induction multiple apoptotic genes. We found forms complex with FOXO1 FOXO3. RNAi-mediated silencing impaired binding promoters cooperative A FOXO3 mutant insensitive inactivation by survival kinases rescued inhibitory effect...
Previous work has identified distinct functions for E2F proteins during a cellular proliferative response including role E2F1-3 in the activation of transcription at G1/S and E2F4-8 repressing same group target genes as cells progress through S phase. We now find that E2F7 E2F8, which are induced by G1/S, can form heterodimer with E2F1 interactions involving DNA-binding domains two proteins. In vitro DNA interaction assays demonstrate formation an E2F1-E2F7 complex, well E2F7-E2F7 complex on...
DNASE1L3, an enzyme highly expressed in DCs, is functionally important for regulating autoimmune responses to self-DNA and chromatin. Deficiency of DNASE1L3 leads development diseases both humans mice. However, despite the well-established causal relationship between immunity, little known about involvement regulation antitumor foundation modern immunotherapy. In this study, we identify as a potentially new regulator immunity tumor suppressor colon cancer. humans, downregulated...
Abstract The difficulty to dissect a complex phenotype of established malignant cells several critical transcriptional programs greatly impends our understanding the transformation. genetic elements required transform some primary human tumorigenic state were described in recent studies. We took advantage global genomic profiling approach and tried go one step further dissection transformation network. sought identify signatures key target genes, which underlie alterations p53, Ras, INK4A...
Due to the poor prognosis of advanced metastatic melanoma, it is crucial find early biomarkers that help identify which melanomas will metastasize. By comparing gene expression data from primary and cutaneous melanoma samples The Cancer Genome Atlas (TCGA), we identified GPC6 among a set genes whose levels can distinguish between regional cutaneous/subcutaneous metastases. Glypicans are thought play role in tumor growth by regulating signaling pathways Wnt, Hedgehogs, fibroblast factors...
// Maria Shatz 1 , Igor Shats 2 Daniel Menendez and Michael A. Resnick Chromosome Stability Group, Laboratory of Molecular Genetics, National Institute Environmental Health Sciences, NIH, Research Triangle Park, NC, USA Department Biomedical Engineering, Duke University, Durham, Correspondence to: Shatz, email: Resnick, Keywords : p53, Toll-like receptor 5, cancer, signal transduction, inflammation Received February 06, 2015 Accepted June 02, Published 10, Abstract The p53 tumor suppressor...
Abstract Mutations in p53 are ubiquitous human tumors. Some mutations not only result loss of wild-type (WT) activity but also grant additional functions, termed “gain function.” In this study, we explore how the status affects immediate response gene activating transcription factor 3 (ATF3) 12-O-tetradecanoylphorbol-13-acetate (TPA)-protein kinase C (PKC) pathway. We show that high doses TPA induce ATF3 a WT p53-independent manner correlating with PKCs depletion and cell death. cells...
The E2F1 transcription factor regulates cell proliferation and apoptosis through the control of a considerable variety target genes. Previous work has detailed role other factors in mediating specificity E2F function. Here we identify NF-YB as novel direct target. Genome-wide expression analysis effects NFYB knockdown on E2F1-mediated identified large group genes that are co-regulated by NFYB. We also provide evidence enhances E2F1-induced apoptosis, suggesting pro-survival function...