WorldCat Identities

Elledge, Stephen Joseph

Overview
Works: 24 works in 57 publications in 2 languages and 191 library holdings
Genres: Conference papers and proceedings 
Roles: Editor, Author
Publication Timeline
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Most widely held works about Stephen Joseph Elledge
 
Most widely held works by Stephen Joseph Elledge
DNA repair, mutagenesis, and other responses to DNA damage : a subject collection from Cold Spring Harbor perspectives in biology( Book )

1 edition published in 2014 in English and held by 128 WorldCat member libraries worldwide

Abstracts of papers presented at the 2002 meeting on the cell cycle, May 15-May 19, 2002( Book )

3 editions published in 2002 in English and held by 14 WorldCat member libraries worldwide

Role of KIP2 in Breast Cancer( Book )

10 editions published between 1997 and 2001 in English and held by 10 WorldCat member libraries worldwide

The cell cycle is regulated by the action of a family of cyclin dependent kinases (Cdks) which catalyze particular cell cycle transitions. Cdks are positively regulated through interaction with cyclins and are negatively regulated through phosphorylation and through association with inhibitory proteins of the CIP/KIP and INK4 families. Our research has focused on the role of p57KIP2 in development and cancer. We have found that p57KIP2 is expressed in a highly cell type specific manner during embryonic development and in adult tissues being most highly expressed in terminally differentiated cells. Through analysis of p57K1P2 deficient mice, however, we have found that p57K1P2 is required for normal development of several tissues including kidney, lends, muscle, and bone. We also discovered the p57 is involved in the human overgrowth and cancer predisposition disease Beckwith-Weidemann Syndrome, BWS. Current studies are aimed at understanding in greater detail the function of p57KIP2 and its possible role in human cancers
Genomic Approaches for Detection and Treatment of Breast Cancer( Book )

8 editions published between 2005 and 2009 in English and held by 8 WorldCat member libraries worldwide

A key part of our research plan has been the development and use of retroviral vectors expressing RNA interference RNAs to identify human genes involved in causing or restraining cancer. In our first progress report we described our efforts to develop shRNA libraries and showed they could be used to identify tumor suppressors. Ultimately our goal is to screen of complex pools of shRNA expressing retroviruses each marked with a bar code that allows the results of the screen to be read out by microarray hybridization. We demonstrated this could be accomplished in enrichment screens for shRNAs that caused cellular transformation and growth in soft agar. However, a key goal has been to identify shRNAs that debilitate or kill cancer cells. In order for this to be possible in complex pools, it is imperative that each vector knock down its target with high penetrance. We have successfully achieved this level of knockdown and can now see particular shRNA expressing viruses drop out of complex pools. We are also developing bar code hybridization methods that allow us to detect over 80% of the viruses in pool. We hope to push this to over 90% using double bar codes. Together the high knockdown vectors together with the bar code hybridization has allowed us to achieve the central goal of this Award. We have taken advantage of our improvements to perform a variety of screens relevant to cancer. These include lethality screens to identify genes that cancer cell lines rely upon to proliferate and survive. We also are performing screens that are identifying genes whose loss gives rise to resistance to tyrosine kinase inhibitors. Finally we are continuing our efforts to identify tumor suppressors in human mammary epithelial cells. We have expanded this to identify oncogenes in the same system. In parallel we are attempting to generate a system through which we can explore the autoimmune phenotype of breast cancer patients. We have generated the peptide display libraries required fo
Analysis of the DNA Damage Signaling Network Important for Prevention of Breast Cancer( Book )

6 editions published between 2002 and 2004 in English and held by 6 WorldCat member libraries worldwide

Women with germline mutations in the breast and ovarian cancer gene 1 (Brca1) have an approximately 50% lifetime risk of developing ovarian cancer and almost 90% chance of breast cancer. Brca1 mutations account for a significant percentage of all breast cancer cases. It appears that the main role for the Brca1 protein in cells is to prevent the accumulation of mutations in key growth regulatory genes in response to DNA damage. BRCA1 is phosphorylated in response to DNA damage by an elaborate surveillance mechanism, called a checkpoint, that detects DNA damage and prevents the accumulation of mutation. We are investigating the role these phosphorylation events play in the regulation of BRCA1. We have mapped phosphorylation sites and will mutate them to determine their function. We are also planning to investigate the mechanism through which the BRCA1 protein localizes to sites of DNA damage within cells
Development of General Methods for Identification of Genes Regulated by Oncogenic Stimuli or DNA Damage( Book )

6 editions published between 1999 and 2001 in English and held by 6 WorldCat member libraries worldwide

In order for cells to prevent mutations, they have an elaborate regulatory network that is capable of sensing and responding to chromosomal aberrations. When damage to chromosomes is detected, cells induce a set of genes that respond to the damage in order to repair the damage and to prevent the cell cycle from progressing. In addition, cells have set up another elaborate regulatory network to ensure that the key events of the cell cycle occur in the correct order with the correct timing. Both the DNA damage response and the cell cycle regulatory pathways are critical to prevent the types of events that generate cancers. Furthermore, both of these pathways operate by the precise regulation of transcription of genes involved in this process. Our proposal has centered around identification of DNA damage inducible genes and genes important in the cell cycle by either retroviral insertions or, more recently by microarray hybridization. We have now identified several hundred genes regulated by these events, either DNA damage or the cell cycle and have learned a great deal about the processes the cell employes to prevent the accumulation of cancer-causing mutations
The Role of Chk2 in Breast Cancer( Book )

4 editions published between 2004 and 2006 in English and held by 4 WorldCat member libraries worldwide

DNA damage activates cellular responses that promote DNA repair, arrest the cell cycle, and in some cases, induce apoptosis (56). Cell cycle arrest allows time for the repair of damaged DNA while apoptosis eliminates cells harboring abnormal DNA. It is widely believed that these DNA damage responses are required for the maintenance of genomic stability and prevention of tumor development (20). The ataxia telangiectasia (A-T) mutated (ATM) gene, which is homologous to the yeast checkpoint gene Tel1, plays a critical role in sensing DNA double strand breaks (DSBs) in mammalian DNA. ATM is a kinase involved in activating the appropriate damage response pathway, leading to either cell cycle arrest or apoptosis, and is therefore a key checkpoint molecule in regulating cell cycle responses to DNA damage (37, 45). Indeed, the majority of phosphorylation events induced by ionizing radiation (IR) are carried out by ATM. Both A-T patients and ATM-deficient mice show defective cell cycle arrest, hypersensitivity to DNA DSBs, and tumor predisposition (4, 21, 52, 53). When cells are damaged by IR, ATM phosphorylates and activates the protein kinase Chk2 (1, 35, 36, 55). Chk2 is a homologue of the Rad53 gene in budding yeast and of the Cds1 gene in fission yeast. Once phosphorylated, activated Chk2 phosphorylates multiple Cdc25 molecules which are thought to inhibit the activation of cyclindependent kinases (7, 10, 34). However, in response to damage induced by UV-irradiation or hydroxyurea, Chk2 is phosphorylated in an ATM-independent manner, possibly by A-T and rad3_ related (ATR) (35, 46). Notably, ATM, ATR, and Chk2 are each able to phosphorylate the tumor suppressor gene p53 (2, 9, 11, 26, 42, 49)
The Role of Ckh2 in Breast Cancer( Book )

2 editions published in 2003 in English and held by 2 WorldCat member libraries worldwide

Breast cancer is a very heterogeneous disease. Many pathological alterations contribute to breast cancer development. Some initiate the cancer formation or accelerate its progression. Our bodies counter DNA damaging stressed form the environment, such as g-irradiation, UV, carcinogens or even from metabolic processes. If DNA damage occurs without being repaired n the genes controlling cell growth or morality, cells will acquire altered growth properties and become transformed and cancer will eventually develop. Fortunately, our bodies have natural defense mechanisms called checkpoints to keep the damaged cells in check so that the damaged genes can be repaired. In this proposal, we plan to study Chk2, one of the central components of the machinery, for its role in managing our defensive system to repair damaged DNA and to suppress cellular transformation. In our studies, we will first generate cells or animals which have no Chk2 expression for use as a model. By studying the responses to DNA damaging agents and the transformation potential, we can determine the significance of Chk2 functions in managing checkpoints and in suppressing transformation. Next, we plan to systematically identify Chk2 substrates and its associated proteins so that we can discover the entire network connecting to Chk2
Proteosomas by Alfred Goldberg( )

2 editions published in 2001 in Spanish and held by 2 WorldCat member libraries worldwide

Sensing and responding to DNA damage( Visual )

1 edition published in 2003 in English and held by 1 WorldCat member library worldwide

Brief Report: Anti–RNPC‐3 Antibodies As a Marker of Cancer‐Associated Scleroderma( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Abstract : Objective: Prior studies have demonstrated an increased risk of cancer‐associated scleroderma in patients with anti–RNA polymerase III (anti–RNAP III) autoantibodies as well as in patients who are triple‐negative for anticentromere (anti‐CENP), anti–topoisomerase I (anti–topo I), and anti–RNAP III (also known as anti‐POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP‐negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC‐3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti–RNPC‐3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients. Methods: Scleroderma patients with cancer were assayed for anti‐CENP, anti–topo I, anti–RNAP III, and anti–RNPC‐3 autoantibodies. Disease characteristics and the cancer–scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer‐associated scleroderma was assessed by logistic regression. Results: Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti–RNAP III, 54 (17.0%) were positive for anti–topo I, and 96 (30.2%) were positive for anti‐CENP. Twelve patients (3.8% of the overall group or 12.2% of CTP‐negative patients) were positive for anti–RNPC‐3. Patients with anti–RNPC‐3 had a short cancer–scleroderma interval (median 0.9 years). Relative to patients with anti‐CENP, patients with anti–RNPC‐3 and those with anti–RNAP III had a >4‐fold increased risk of cancer within 2 years of scleroderma onset (for anti–RNPC‐3–positive patients, odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.10–16.9 [ P  = 0.037]; for anti–RNAP III–positive patients, OR 4.49, 95% CI 1.98–10.2 [ P  < 0.001]). Patients with anti–RNPC‐3 had severe restrictive lung disease, gastrointestinal disease, Raynaud's phenomenon, and myopathy. Conclusion: Anti–RNPC‐3 autoantibodies, similar to anti–RNAP III autoantibodies, are associated with an increased risk of cancer at the onset of scleroderma. These data suggest the possibility of cancer‐induced autoimmunity in this subset of patients with scleroderma
Identification and characterization of genes involved in mutagenesis in Escherichia coli by Stephen Joseph Elledge( )

1 edition published in 1983 in English and held by 1 WorldCat member library worldwide

Involvement of 53BP1, a p43 Binding Protein, in Chk2 Phosphorylation of p53 and DNA Damage Cell Cycle Checkpoints( )

1 edition published in 2003 in English and held by 1 WorldCat member library worldwide

53BP1 binds to the tumor suppressor protein p53 and has a potential role in DNA damage responses. We used small interfering RNA (siRNA) directed against 53BP1 in mammalian cells to demonstrate that 53BP1 is a key transducer of the DNA damage checkpoint signal. 53BP1 was required for p33 accumulation, G2-M checkpoint arrest, and the intra-S-phase checkpoint in response to ionizing radiation. 53BP1 played a partially redundant role in phosphorylation of the downstream checkpoint effector proteins Brca1 and Chk2 but was required for the formation of Brca1 foci in a hierarchical branched pathway for the recruitment of repair and signaling proteins to site of DNA damage
Reply( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Adventures in mammalian genetics by Stephen Joseph Elledge( Visual )

1 edition published in 2008 in English and held by 1 WorldCat member library worldwide

Using Genetics and Genomics for the Detection and Treatment of Breast Cancer( )

1 edition published in 2009 in English and held by 1 WorldCat member library worldwide

The evolution of human cells into malignant derivatives is driven by the aberrant function of genes that positively and negatively regulate various aspects of the cancer phenotype, including altered responses to mitogenic and cytostatic signals, resistance to programmed cell death, immortalization, neoangiogenesis, and invasion and metastasis(1). The integrity of these gene functions is compromised by substantial genetic and epigenetic alterations observed in most cancer cell genomes. To understand the tumorigenic process, it is imperative to identify and characterize the genes that provide tumor cells with the capabilities requisite for their initiation and progression. However, the identities of those genes that contribute to the tumor phenotype are often concealed by the frequent alterations in genes that play no role in tumorigenesis. Identifying genes that restrain tumorigenesis (tumor suppressors) has proven especially challenging due to their recessive nature. Further complicating their discovery are the multifaceted mechanisms by which tumor suppressor genes are inactivated including changes in copy number and structure, point mutations, and epigenetic alterations(2). Moreover, the mechanisms by which tumor suppressor genes are inhibited may vary between tumors. With this in mind, a variety of molecular and cytogenetic technologies have been used to establish extensive catalogs of genetic alterations within human cancers(3,4). And while it is generally accepted that highly recurrent aberrations signify changes that are important for tumor development, the causal perturbations underlying tumor genesis are often confounded by the extensive size of alterations and the large number that are incidental to the tumor phenotypes. As such, new strategies to delineate genes with functional relevance to tumor initiation and development are essential to understanding these processes
How aneuploidy drives cancer( Visual )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

(CIT): Neuploidy has been recognized as a hallmark of cancer for more than 100 years, yet no general theory has emerged to explain the recurring patterns of aneuploidy in cancer. Dr. Elledge's laboratory developed the Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor gene (TSG) or an oncogene (OG). By analyzing more than 8,200 tumor-normal pairs, his lab has provided statistical evidence suggesting that many more genes possess cancer-driver properties than anticipated, forming a continuum of oncogenic potential. These genes represent the vast majority of cancer drivers, and the genetic networks they drive are a focus of future cancer system-biological approaches to cancer research. By integrating the driver predictions with information on somatic copy-number alterations, his lab has found that the distribution and the potency of TSGs (STOP genes), OGs, and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy-number variation characteristic of cancer genomes. The lab proposes that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity. Dr. Elledge and his lab are now assessing how aneuploidy drives cancer and the potency with which it does so. They have found that, in many cases, aneuploidy predicts survival better than do mutational drivers or existing clinical parameters. They have also discovered that different classes of aneuploidy drive transcriptional programs for two hallmarks of cancer. Aneuploidy promotes a cell-proliferation program and inhibits the infiltration of immune cells leading to immune evasion. Melanoma patients with tumors exhibiting high aneuploidy show poorer responses to immunotherapy with anti-CTLA4 antibodies. Dr. Elledge and his lab are now exploring which genes in recurring amplicons drive proliferation
Cancer : BRCA2 enters the fray by John H Wilson( )

1 edition published in 2002 in English and held by 0 WorldCat member libraries worldwide

Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes by Lee Zou( )

1 edition published in 2003 in English and held by 0 WorldCat member libraries worldwide

Cancer : p53 sends nucleotides to repair DNA by Guillermina Lozano( )

1 edition published in 2000 in English and held by 0 WorldCat member libraries worldwide

 
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Alternative Names
Elledge, Steve

Stephen Elledge Amerikaans klinische genetica

Stephen J. Elledge US-amerikanischer Genetiker

Стивен Элледж американский генетик

ستيفن إليدج

斯蒂芬·埃利奇

Languages