Research Topics
Species | ROBERT R CLARKESummaryAffiliation: Georgetown University Country: USA Publications
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Publications
GX15-070 (Obatoclax) Induces Apoptosis and Inhibits Cathepsin D- and L-Mediated Autophagosomal Lysis in Antiestrogen-Resistant Breast Cancer CellsJessica L Schwartz-Roberts
Corresponding Author Robert Clarke, Department of Oncology, Georgetown University School of Medicine, Research Building W405A, 3970 Reservoir Road NW, Washington, DC 20057
Mol Cancer Ther 12:448-59. 2013..Our data highlight a new mechanism of GX15-070-induced cell death that could be used to design novel therapeutic interventions for antiestrogen resistant breast cancer. Mol Cancer Ther; 12(4); 448-59. ©2013 AACR...- Endoplasmic reticulum stress, the unfolded protein response, autophagy, and the integrated regulation of breast cancer cell fateRobert Clarke
Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057, USA
Cancer Res 72:1321-31. 2012..Central topologic features of the signaling network that integrate cell-fate regulation and decision execution are discussed... - Identifying cancer biomarkers by network-constrained support vector machinesLi Chen
Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA, USA
BMC Syst Biol 5:161. 2011..Nonetheless, the variables in multivariable classifiers should synergistically interact to produce more effective classifiers than individual biomarkers... - Reverse engineering module networks by PSO-RNN hybrid modelingYuji Zhang
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
BMC Genomics 10:S15. 2009.... - AIB1 gene amplification and the instability of polyQ encoding sequence in breast cancer cell linesLee Jun C Wong
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
BMC Cancer 6:111. 2006..The purpose of this study is to investigate the sequence variation of poly Q encoding region in breast cancer cell lines at single molecule level, and to determine if the sequence variation is related to AIB1 gene amplification... - Motif-guided sparse decomposition of gene expression data for regulatory module identificationTing Gong
Bradley Department of Electrical and Computer Engineering, Virginia Tech, Arlington, VA 22203, USA
BMC Bioinformatics 12:82. 2011..However, traditional gene clustering often yields unsatisfactory results for regulatory module identification because the resulting gene clusters are co-expressed but not necessarily co-regulated... - Motif-directed network component analysis for regulatory network inferenceChen Wang
Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA, USA
BMC Bioinformatics 9:S21. 2008..We propose a new approach, motif-directed NCA (mNCA), to integrate motif information and gene expression data to infer regulatory networks... - Knowledge-guided gene ranking by coordinative component analysisChen Wang
Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA, USA
BMC Bioinformatics 11:162. 2010..However, current integration strategies are often heuristic and fail to incorporate fully the true interplay between biological knowledge and gene expression data... - Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological dataYuji Zhang
Lombardi Comprehensive Cancer Center, Georgetown University, 4000 Reservoir Rd, Washington, DC, USA
BMC Bioinformatics 9:203. 2008..The data include time course gene expression profiles, genome-wide location analysis data, binding sequence data, and gene ontology (GO) information... - Knowledge-guided multi-scale independent component analysis for biomarker identificationLi Chen
Department of Electrical and Computer Engineering, Virginia Polytechnic Institute and State University, Arlington, VA, USA
BMC Bioinformatics 9:416. 2008..In this paper, we develop a novel strategy, namely knowledge-guided multi-scale independent component analysis (ICA), to first infer regulatory signals and then identify biologically relevant biomarkers from microarray data... - caBIG VISDA: modeling, visualization, and discovery for cluster analysis of genomic dataYitan Zhu
Department of Electrical and Computer Engineering, Virginia Polytechnic and State University, Arlington, VA 22203, USA
BMC Bioinformatics 9:383. 2008.... 
Multidrug resistance/P-glycoprotein and breast cancer: review and meta-analysisRobert Clarke
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
Semin Oncol 32:S9-15. 2005..Future studies should also take into account the potentially multifactorial nature of multidrug resistance...- Antiestrogen resistance in breast cancer and the role of estrogen receptor signalingRobert Clarke
Department of Oncology and Vincent T Lombardi Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Oncogene 22:7316-39. 2003..The network also may involve signaling through ras and MAPK, implicating crosstalk with growth factors and cytokines. Ultimately, signaling affects the expression/function of the proliferation and/or apoptotic machineries... - Cannibalism, cell survival, and endocrine resistance in breast cancerRobert Clarke
Department of Oncology, W405A Research Building, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057, USA
Breast Cancer Res 13:311. 2011.... - Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cellsRobert Clarke
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
J Steroid Biochem Mol Biol 114:8-20. 2009..Signaling proceeds through BCL2 gene family members and BECN1 ultimately to regulate cell fate... - Association of interferon regulatory factor-1, nucleophosmin, nuclear factor-kappaB, and cyclic AMP response element binding with acquired resistance to Faslodex (ICI 182,780)Zhiping Gu
Vincent T Lombardi Cancer Center and Department of Oncology, Georgetown University School of Medicine, Washington, DC 20007, USA
Cancer Res 62:3428-37. 2002..Thus, some breast cancer cells may survive antiestrogen treatment by bypassing specific growth inhibitory signals induced by antagonist-occupied estrogen receptors... - Human X-box binding protein-1 confers both estrogen independence and antiestrogen resistance in breast cancer cell linesBianca P Gomez
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Rd, NW, Washington, DC 20057, USA
FASEB J 21:4013-27. 2007..XBP1 and/or the UPR may be a useful molecular target for the development of novel predictive and therapeutic strategies in breast cancer... - BCL2 and CASP8 regulation by NF-kappaB differentially affect mitochondrial function and cell fate in antiestrogen-sensitive and -resistant breast cancer cellsRuchi Nehra
Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057, USA
FASEB J 24:2040-55. 2010.... - The nuclear factor kappa B inhibitor parthenolide restores ICI 182,780 (Faslodex; fulvestrant)-induced apoptosis in antiestrogen-resistant breast cancer cellsRebecca B Riggins
Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Room W405A Research Building, 3970 Reservoir Road Northwest, Washington, DC 20057, USA
Mol Cancer Ther 4:33-41. 2005..Because parthenolide has shown safety in Phase I clinical trials, these findings have direct clinical relevance and provide support for the design of clinical studies combining antiestrogens and parthenolide in ER-positive breast cancer... - IFNgamma restores breast cancer sensitivity to fulvestrant by regulating STAT1, IFN regulatory factor 1, NF-kappaB, BCL2 family members, and signaling to caspase-dependent apoptosisYanxia Ning
Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
Mol Cancer Ther 9:1274-85. 2010..These observations support the exploration of clinical trials combining antiestrogens and compounds that can induce IRF1, such as IFNgamma, for the treatment of some ER-positive breast cancers... - interferon regulatory factor-1 mediates the proapoptotic but not cell cycle arrest effects of the steroidal antiestrogen ICI 182,780 (faslodex, fulvestrant)Kerrie B Bouker
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia 20007, USA
Cancer Res 64:4030-9. 2004..These data identify a novel mechanism of antiestrogen resistance and implicate IRF-1 as a key component in signaling some ER-mediated effects on apoptosis/cell survival... - Expression patterns among interferon regulatory factor-1, human X-box binding protein-1, nuclear factor kappa B, nucleophosmin, estrogen receptor-alpha and progesterone receptor proteins in breast cancer tissue microarraysYuelin Zhu
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
Int J Oncol 28:67-76. 2006..018) is observed. An inverse correlation exists between IRF-1n and NFkappaB (p=0.034). All four proteins are detected in breast tumors and their expression patterns support their role(s) in a key signaling network... - Block principal component analysis with application to gene microarray data classificationAiyi Liu
Biostatistics Unit, Lombardi Cancer Center, Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007, USA
Stat Med 21:3465-74. 2002..The method is illustrated with the well-known National Cancer Institute database of 60 human cancer cell lines data (NCI60) of gene microarray expressions, in the context of classification of cancer cell lines... - Development and validation of a method for using breast core needle biopsies for gene expression microarray analysesMatthew Ellis
Department of Oncology, Georgetown University School of Medicine, Washington, DC 20007, USA
Clin Cancer Res 8:1155-66. 2002..Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies... - Dietary modulation of pregnancy estrogen levels and breast cancer risk among female rat offspringLeena Hilakivi-Clarke
Department of Oncology, Lombardi Cancer Center, Washington, DC 20007, USA
Clin Cancer Res 8:3601-10. 2002.... - ERRgamma mediates tamoxifen resistance in novel models of invasive lobular breast cancerRebecca B Riggins
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, District of Columbia 20057, USA
Cancer Res 68:8908-17. 2008..These data support a role for ERRgamma/AP1 signaling in the development of TAM resistance and suggest that expression of ERRgamma may be a marker of poor TAM response... - Antiestrogens, aromatase inhibitors, and apoptosis in breast cancerRebecca B Riggins
Department of Oncology and Physiology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
Vitam Horm 71:201-37. 2005..Finally, we discuss the evidence supporting a role for apoptotic defects in acquired and de novo antiestrogen resistance... - Mechanisms mediating the effects of prepubertal (n-3) polyunsaturated fatty acid diet on breast cancer risk in ratsLeena Hilakivi-Clarke
Department of Oncology, Georgetown University Medical Center, Washington, DC 20057, USA
J Nutr 135:2946S-2952S. 2005.... - Estrogen receptor alpha positive breast tumors and breast cancer cell lines share similarities in their transcriptome data structuresYuelin Zhu
Lombardi Comprehensive Cancer Center and Departments of Oncology, Georgetown University School of Medicine, Washington, DC, USA
Int J Oncol 29:1581-9. 2006.... - Do estrogens always increase breast cancer risk?Leena Hilakivi-Clarke
Lombardi Cancer Center and Department of Oncology, Georgetown University, Room W405, 3970 Reservoir Road NW, Washington, DC 20007, USA
J Steroid Biochem Mol Biol 80:163-74. 2002..We further propose that the timing of estrogenic exposures may play at least as important a role in affecting breast cancer risk as life-time exposure... - Classification algorithms for phenotype prediction in genomics and proteomicsHabtom W Ressom
Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd NW, Washington, DC 20057, USA
Front Biosci 13:691-708. 2008..The selected features are presented to a classifier for phenotype prediction... - Cadmium mimics the in vivo effects of estrogen in the uterus and mammary glandMichael D Johnson
Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA
Nat Med 9:1081-4. 2003..In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland... - C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pumpFabio Leonessa
Department of Oncology and Lombardi Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Road Northwest, Washington, DC 20007, USA
J Med Chem 45:390-8. 2002..These data identify C-7-substituted progesterone analogues and 5, in particular, as rationally designed antiPgp compounds worthy of further evaluation/development... - The role of X-box binding protein-1 in tumorigenicityAyesha N Shajahan
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D C, USA
Drug News Perspect 22:241-6. 2009..Furthermore, combining inhibitors of XBP-1 with other anti-UPR drugs may enhance the activity of some antineoplastic therapies... - Evaluation of gene expression profile of keratinocytes in response to JP-8 jet fuelLuis A Espinoza
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA
Toxicol Appl Pharmacol 200:93-102. 2004..Gene expression data from these studies can be used to build accurate predictive models that separate different molecular profiles. The data establish the use and effectiveness of these approaches for future prospective studies... - Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosisKerrie B Bouker
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Carcinogenesis 26:1527-35. 2005..03). These data establish a functional role for IRF-1 in the growth suppression of breast cancer cells and strongly implicate IRF-1 as a tumor suppressor gene in breast cancer that acts, independent of p53, to control apoptosis... - The properties of high-dimensional data spaces: implications for exploring gene and protein expression dataRobert Clarke
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Nat Rev Cancer 8:37-49. 2008..From the perspective of translational science, this Review discusses the properties of high-dimensional data spaces that arise in genomic and proteomic studies and the challenges they can pose for data analysis and interpretation... - Functionally active estrogen receptor isoform profiles in the breast tumors of African American women are different from the profiles in breast tumors of Caucasian womenIndra Poola
Department of Anatomy, Howard University School of Medicine, Washington, DC 20059, USA
Cancer 94:615-23. 2002..The molecular factors responsible for these tumor characteristics are mostly unknown... - Iterative normalization of cDNA microarray dataYue Wang
Department of Electrical Engineering and Computer Science, The Catholic University of America, Washington, DC 20064, USA
IEEE Trans Inf Technol Biomed 6:29-37. 2002..In this way, the two processes bootstrap one another. We evaluate the technique on real microarray data from breast cancer cell lines and complement the experiment with a data cluster visualization study... - Orphan nuclear receptors in breast cancer pathogenesis and therapeutic responseRebecca B Riggins
Lombardi Comprehensive Cancer Center and Department of Oncology Department of Physiology and Biophysics, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA
Endocr Relat Cancer 17:R213-31. 2010..We also propose that a clearer understanding of the function of orphan nuclear receptors in mammary gland development and normal mammary tissues could significantly improve our ability to diagnose, treat, and prevent breast cancer... 
The proapoptotic molecule BLID interacts with Bcl-XL and its downregulation in breast cancer correlates with poor disease-free and overall survivalConstantinos G Broustas
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia 20057, USA
Clin Cancer Res 16:2939-48. 2010..BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer...- The A4396G polymorphism in interferon regulatory factor 1 is frequently expressed in breast cancer cell linesKerrie B Bouker
Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057, USA
Cancer Genet Cytogenet 175:61-4. 2007..001), leading to a significant difference in genotype distribution between these populations (P = 0.002)... - Inferring network interactions using recurrent neural networks and swarm intelligenceHabtom W Ressom
Dept. of Biostat, Bioinf, and Biomath, Georgetown Univ, Washington, DC 20057, USA
Conf Proc IEEE Eng Med Biol Soc 1:4241-4. 2006..The results indicate that the algorithm has a promising potential to infer complex interactions such as gene regulatory networks from time-series gene expression data... - Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicityAyesha N Shajahan
Department of Oncology, Lombardi Comprehensive Cancer Center, and Departments of Physiology and Biophysics, Georgetown University, College of Medicine, Washington, D C 20057, USA
J Biol Chem 282:5934-43. 2007..Collectively, our findings underscore the importance of CAV1 phosphorylation in apoptosis and suggest that events that negate CAV1 tyrosine phosphorylation may contribute to anti-microtubule drug resistance... - Frequent loss of heterozygosity at the interferon regulatory factor-1 gene locus in breast cancerLuciane R Cavalli
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
Breast Cancer Res Treat 121:227-31. 2010..00; P = 0.003; n = 273 cases) and risk of death (OR = 4.18; P = 0.004; n = 191 cases). Our findings strongly imply a tumor suppressor role for the IRF1 gene in breast cancer...
Research Grants
- Molecular Analysis of Human Breast CancerRobert Clarke; Fiscal Year: 2007..AIM 4: We will use tissue arrays (multiple cores from archival tissues arrayed on glass slides) to validate and optimize the performance of these classifiers in a retrospective prognostic study of human breast tumors. ..
- ESTROGEN INDUCED PROGRESSION IN BREAST CANCERRobert Clarke; Fiscal Year: 2001....
- ESTROGEN-INDUCED PROGRESSION IN HUMAN BREAST CANCERRobert Clarke; Fiscal Year: 1993....
- Endocrine resistance in breast cancerROBERT R CLARKE; Fiscal Year: 2010....