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3. Single-nuclei characterization of pervasive transcriptional signatures across organs in response to COVID-19

Author

Granados, Alejandro, Huang, Franklin W, Huang, Guo N, Kattah, Michael G, Peng, Tien, Keller, Andreas, Pisco, Angela Oliveira, Neff, Norma, Wang, Bruce, Song, Hanbing, Bucher, Simon, Chen, Ann T, Agrawal, Aditi, Allen, Nancy, Hyams, Benjamin, Burhan, Deviana, Detweiler, Angela, Huynh, Shelly, Ludwig, Nicole, Morri, Maurizio, Schultz-Schaeffer, Walter, Tan, Michelle, Weinstein, Hannah NW, Yan, Rose, Mekonen, Honey, Yan, Rose Jia, McGeever, Aaron, Chen, Xiaoxin, Galdos, Francisco, Mennillo, Elvira, Murti, Abhishek, Rao, Poorvi, Rusu, Lulia, Xie, Jamie, Liu, Jonathan, Huang, Sharon S, Tarashansky, Alexander, Awayan, Kyle, Granados, Alejandro A, and Huang, Franklin

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Lung, Infectious Diseases, Emerging Infectious Diseases, Coronaviruses, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, COVID-19, SARS-CoV-2, Endothelial Cells, RNA, Viral, COVID, cell atlas, transcriptomics, RNA-seq, single-cell, transcriptional regulation, Human, COVID Tissue Atlas Consortium, epidemiology, genetics, genomics, global health, human, Biochemistry and Cell Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundInfection by coronavirus SARS-CoV2 is a severe and often deadly disease that has implications for the respiratory system and multiple organs across the human body. While the effects in the lung have been extensively studied, less is known about the impact COVID-19 has across other organs.MethodsHere, we contribute a single-nuclei RNA-sequencing atlas comprising six human organs across 20 autopsies where we analyzed the transcriptional changes due to COVID-19 in multiple cell types. The integration of data from multiple organs enabled the identification of systemic transcriptional changes.ResultsComputational cross-organ analysis for endothelial cells and macrophages identified systemic transcriptional changes in these cell types in COVID-19 samples. In addition, analysis of gene modules showed enrichment of specific signaling pathways across multiple organs in COVID-19 autopsies.ConclusionsAltogether, the COVID Tissue Atlas enables the investigation of both cell type-specific and cross-organ transcriptional responses to COVID-19, providing insights into the molecular networks affected by the disease and highlighting novel potential targets for therapies and drug development.FundingThe Chan-Zuckerberg Initiative, The Chan-Zuckerberg Biohub.

Published
2023

5. Jagged2 targeting in lung cancer activates anti-tumor immunity via Notch-induced functional reprogramming of tumor-associated macrophages

Author

Mandula, Jay K., Sierra-Mondragon, Rosa A., Jimenez, Rachel V., Chang, Darwin, Mohamed, Eslam, Chang, Shiun, Vazquez-Martinez, Julio A., Cao, Yu, Anadon, Carmen M., Lee, Sae Bom, Das, Satyajit, Rocha-Munguba, Léo, Pham, Vincent M., Li, Roger, Tarhini, Ahmad A., Furqan, Muhammad, Dalton, William, Churchman, Michelle, Moran-Segura, Carlos M., Nguyen, Jonathan, Perez, Bradford, Kojetin, Douglas J., Obermayer, Alyssa, Yu, Xiaoqing, Chen, Ann, Shaw, Timothy I., Conejo-Garcia, Jose R., and Rodriguez, Paulo C.

Published
2024
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11. Honokiol Exhibits Anti-NLRP3 Inflammasome and Antimicrobial Properties in Neisseria gonorrhoeae-Infected Macrophages

Author

Hua, Kuo-Feng, primary, Hsu, Hsien-Ta, additional, Huang, May-Shu, additional, Chiu, Hsiao-Wen, additional, Wong, Wei-Ting, additional, Peng, Chien-Hsiu, additional, Lin, Yu-Bei, additional, Chen, Ann, additional, Wang, Chien-Chun, additional, Hsu, Chung-Hua, additional, Wu, Chun-Hsien, additional, Lin, Wen-Yu, additional, Ho, Chen-Lung, additional, and Li, Lan-Hui, additional

Published
2024
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12. Abstract A004: Patterns of lncRNA-regulated gene expression in high-grade serous ovarian carcinomas

Author

Reid, Brett M., primary, Chen, Ann, additional, Chen, Zhihua, additional, Karreth, Florian A., additional, Kanetsky, Peter, additional, Permuth, Jennifer B., additional, Saglam, Ozlen, additional, Teer, Jamie K., additional, Yu, Xiaoqing, additional, Gayther, Simon, additional, Goode, Ellen, additional, Pharoah, Paul, additional, Sellers, Thomas A., additional, Lawrenson, Kate, additional, and Tyrer, Jonathan, additional

Published
2024
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15. Targeted Therapeutics for Rare Disorders

Author

Keeling, Kim M., primary, Leier, Andre, additional, Bedwell, David M., additional, Chen, Ann T., additional, Kesterson, Robert A., additional, Marquez Lago, Tatiana T., additional, Müller, Ulrich F., additional, Zhou, Jiangbing, additional, Popplewell, Linda, additional, and Wallis, Deeann, additional

Published
2022
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17. Detection of residual rifampicin in urine via fluorescence quenching of gold nanoclusters on paper

Author

Chatterjee, Krishnendu, Kuo, Chiung Wen, Chen, Ann, and Chen, Peilin

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Biomedical and Clinical Sciences, Industrial Biotechnology, Medical Biotechnology, Agricultural Biotechnology, Infection, Good Health and Well Being, Animals, Antibiotics, Antitubercular, Biosensing Techniques, Cattle, Gold, Humans, Limit of Detection, Metal Nanoparticles, Paper, Point-of-Care Systems, Rifampin, Serum Albumin, Bovine, Spectrometry, Fluorescence, Fluorescent biosensors, Fluorescence quenching, Gold nanocluster, Rifampicin detection, TB drug monitoring, Wax-printed paper platform, Technology, Nanoscience & Nanotechnology, Agricultural biotechnology, Industrial biotechnology, Medical biotechnology
Abstract

BackgroundRifampicin or rifampin (R) is a common drug used to treat inactive meningitis, cholestatic pruritus and tuberculosis (TB), and it is generally prescribed for long-term administration under regulated dosages. Constant monitoring of rifampicin is important for controlling the side effects and preventing overdose caused by chronic medication. In this study, we present an easy to use, effective and less costly method for detecting residual rifampicin in urine samples using protein (bovine serum albumin, BSA)-stabilized gold nanoclusters (BSA-Au NCs) adsorbed on a paper substrate in which the concentration of rifampicin in urine can be detected via fluorescence quenching. The intensity of the colorimetric assay performed on the paper-based platforms can be easily captured using a digital camera and subsequently analyzed.ResultsThe decreased fluorescence intensity of BSA-Au NCs in the presence of rifampicin allows for the sensitive detection of rifampicin in a range from 0.5 to 823 µg/mL. The detection limit for rifampicin was measured as 70 ng/mL. The BSA-Au NCs were immobilized on a wax-printed paper-based platform and used to conduct real-time monitoring of rifampicin in urine.ConclusionWe have developed a robust, cost-effective, and portable point-of-care medical diagnostic platform for the detection of rifampicin in urine based on the ability of rifampicin to quench the fluorescence of immobilized BSA-Au NCs on wax-printed papers. The paper-based assay can be further used for the detection of other specific analytes via surface modification of the BSA in BSA-Au NCs and offers a useful tool for monitoring other diseases.

Published
2015

21. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

Author

Lawrenson, Kate, Iversen, Edwin S, Tyrer, Jonathan, Weber, Rachel Palmieri, Concannon, Patrick, Hazelett, Dennis J, Li, Qiyuan, Marks, Jeffrey R, Berchuck, Andrew, Lee, Janet M, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Bandera, Elisa V, Bean, Yukie, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Chen, Ann, Chen, Zhihua, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Plisiecka-Halasa, Joanna, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Eccles, Diana, Easton, Douglas T, Edwards, Robert P, Eilber, Ursula, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus, Hosono, Satoyo, Jakubowska, Anna, Paul, James, Jensen, Allan, Karlan, Beth Y, Kjaer, Susanne Kruger, Kelemen, Linda E, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Krakstad, Camilla, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Cannioto, Rikki, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, Nevanlinna, Heli, McNeish, Iain, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Narod, Steven A, Nedergaard, Lotte, Ness, Roberta B, Azmi, Mat Adenan Noor, Odunsi, Kunle, and Olson, Sara H

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Biotechnology, Cancer, Human Genome, Ovarian Cancer, Prevention, Rare Diseases, Genetic Testing, Genetics, Aetiology, 2.1 Biological and endogenous factors, Carcinoma, Ovarian Epithelial, Case-Control Studies, Checkpoint Kinase 2, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Australian Cancer Study, Australian Ovarian Cancer Study Group, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.

Published
2015

22. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci

Author

Coetzee, Simon G, Shen, Howard C, Hazelett, Dennis J, Lawrenson, Kate, Kuchenbaecker, Karoline, Tyrer, Jonathan, Rhie, Suhn K, Levanon, Keren, Karst, Alison, Drapkin, Ronny, Ramus, Susan J, Consortium, The Consortium of Investigators of Modifiers of BRCA1 2 The Ovarian Cancer Association, Couch, Fergus J, Offit, Kenneth, Chenevix-Trench, Georgia, Monteiro, Alvaro NA, Antoniou, Antonis, Freedman, Matthew, Coetzee, Gerhard A, Pharoah, Paul DP, Noushmehr, Houtan, Gayther, Simon A, Anton-Culver, Hoda, Antonenkova, Natalia, Baker, Helen, Bandera, Elisa V, Bean, Yukie, Beckmann, Matthias W, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bruinsma, Fiona, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Chen, Ann, Chen, Zhihua, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, Dennis, Joe, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana, Easton, Douglas F, Edwards, Robert P, Eilber, Ursula, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goode, Ellen L, Goodman, Marc T, Grownwald, Jacek, Harrington, Patricia, Harter, Philipp, Hasmad, Hanis Nazihah, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Estrid, Hogdall, Claus, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, James, Paul, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kjaer, Susanne Kruger, Kelemen, Linda E, Kellar, Melissa, Kelley, Joseph L, Kiemeney, Lambertus A, Krakstad, Camilla, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, and Lissowska, Jolanta

Subjects
Biological Sciences, Genetics, Rare Diseases, Prevention, Human Genome, Ovarian Cancer, Biotechnology, Cancer, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Chromatin, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Histones, Humans, Organ Specificity, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Ovarian Cancer Association Consortium, The Consortium of Investigators of Modifiers of BRCA1/2, Ovarian Cancer Association Consortium The Consortium of Investigators of Modifiers of BRCA1/2, Medical and Health Sciences, Genetics & Heredity
Abstract

Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.

Published
2015

23. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

Author

Chornokur, Ganna, Lin, Hui-Yi, Tyrer, Jonathan P, Lawrenson, Kate, Dennis, Joe, Amankwah, Ernest K, Qu, Xiaotao, Tsai, Ya-Yu, Jim, Heather SL, Chen, Zhihua, Chen, Ann Y, Permuth-Wey, Jennifer, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Bruinsma, Fiona, Bandera, Elisa V, Bean, Yukie T, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bunker, Clareann H, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, du Bois, Andreas, Despierre, Evelyn, Dicks, Ed, Doherty, Jennifer A, Dörk, Thilo, Dürst, Matthias, Easton, Douglas F, Eccles, Diana M, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harrington, Patricia, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Claus K, Hogdall, Estrid, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kelemen, Linda E, Kellar, Mellissa, Kiemeney, Lambertus A, Krakstad, Camilla, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lim, Boon Kiong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Iain, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Moysich, Kirsten B, Ness, Roberta B, Nevanlinna, Heli, Eilber, Ursula, Odunsi, Kunle, Olson, Sara H, and Orlow, Irene

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, Ovarian Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Black or African American, Alleles, Asian, Biological Transport, Carcinoma, Ovarian Epithelial, Carrier Proteins, Case-Control Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Neoplasms, Glandular and Epithelial, Odds Ratio, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk, Georgia Chenevix-Trench, AOCS management group, General Science & Technology
Abstract

BackgroundDefective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.MethodsIn total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q

Published
2015

24. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

Author

Jim, Heather SL, Lin, Hui-Yi, Tyrer, Jonathan P, Lawrenson, Kate, Dennis, Joe, Chornokur, Ganna, Chen, Zhihua, Chen, Ann Y, Permuth-Wey, Jennifer, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia, Bruinsma, Fiona, Bandera, Elisa V, Bean, Yukie T, Beckmann, Matthias W, Bisogna, Maria, Bjorge, Line, Bogdanova, Natalia, Brinton, Louise A, Brooks-Wilson, Angela, Bunker, Clareann H, Butzow, Ralf, Campbell, Ian G, Carty, Karen, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cunningham, Julie M, Cybulski, Cezary, Dansonka-Mieszkowska, Agnieszka, du Bois, Andreas, Despierre, Evelyn, Sieh, Weiva, Doherty, Jennifer A, Dörk, Thilo, Dürst, Matthias, Easton, Douglas F, Eccles, Diana M, Edwards, Robert P, Ekici, Arif B, Fasching, Peter A, Fridley, Brooke L, Gao, Yu-Tang, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harter, Philipp, Hasmad, Hanis N, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Hogdall, Claus K, Hogdall, Estrid, Hosono, Satoyo, Iversen, Edwin S, Jakubowska, Anna, Jensen, Allan, Ji, Bu-Tian, Karlan, Beth Y, Kellar, Melissa, Kiemeney, Lambertus A, Krakstad, Camilla, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Vierkant, Robert A, Lambrechts, Diether, Lambrechts, Sandrina, Le, Nhu D, Lee, Alice W, Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A, Liang, Dong, Lim, Boon Kiong, Lissowska, Jolanta, Lu, Karen, Lubinski, Jan, Lundvall, Lene, Massuger, Leon FAG, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, McNeish, Ian, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Thomsen, Lotte, Moysich, Kirsten B, Ness, Roberta B, Nevanlinna, Heli, Eilber, Ursula, Odunsi, Kunle, Olson, Sara H, Orlow, Irene, and Orsulic, Sandra

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Health Services and Systems, Health Sciences, Oncology and Carcinogenesis, Cancer, Orphan Drug, Prevention, Sleep Research, Rare Diseases, Ovarian Cancer, Aetiology, 2.1 Biological and endogenous factors, Georgia Chenevix-Trench on behalf of the AOCS management group 95, 96
Abstract

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10-4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.

Published
2015

27. 698 Safety and tolerability of magrolimab in combination with taxanes in patients with solid tumors

Author

Juan-Videl, Oscar, primary, Chiu, Joanne, additional, Vaishampayan, Ulka N, additional, Joshi, Rohit, additional, Furqan, Muhammad, additional, Rainey, Natalie, additional, Fang, Bruno, additional, Lawler, William, additional, Vicuna, Brian, additional, Xu, Wen, additional, Shao, Jiang, additional, Shihadeh, Fadi, additional, Chen, Ann, additional, Sills, Aoife, additional, Lopez, Estibaliz, additional, and Adams, Sylvia, additional

Published
2023
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29. People v. Brunetti: Issues of Homicide, Conspiracy, Gun Control, and the Right to Bear Arms. Official Materials for the California Mock Trial Program.

Author

Constitutional Rights Foundation, Los Angeles, CA. and Chen, Ann

Abstract

Each year the Constitutional Rights Foundation creates a mock trial that addresses serious matters facing young people. This year the lesson confronts the recent shootings at U.S. schools and the subsequent criminal trials. The nature of such violence and its causes including unresolved peer conflict, questions of responsibility, peer pressure, easy access to firearms, and drug and alcohol abuse are incorporated in a frank and serious manner. The lessons and resources included in the packet offer supplementary methods to address many of the topics contained in "People v. Brunetti." The packet is divided into the following sections: "Program Objectives" (both for students and schools); "Code of Ethics"; "Introduction to the 1998-99 California Mock Trial Program"; "Classroom Materials"; "Introduction to 1998-99 California Mock Competition"; "Fact Situation" (Charges, Evidence, Stipulations); "Pretrial Motion and Constitutional Issue" (Arguments, Sources, Legal Authorities, The Mock Pretrial Motion Hearing); "Witness Statements" (Official Diagrams); "The Form and Substance of a Trial"; "Team Role Descriptions"; "Procedures for Presenting a Mock Trial Case"; "Diagram: A Typical Courtroom"; "Mock Trial Simplified Rules of Evidence" (Allowable Evidentiary Objections, Summary of Allowable Objections for the 1998-99 Mock Trial); and "Official Judge, Scorer and Teacher Information Packet" (Teacher's Packet Lesson Plans, Rules of Competition, Order of Events, Judge and Attorney Instructions, Judge's Narrative for Trial Instruction, Scoring Materials, Forms). (BT)

Published
1998

31. SYST-03 PHASE 1B STUDY OF AVELUMAB AND WHOLE BRAIN RADIOTHERAPY (WBRT) IN PATIENTS WITH LEPTOMENINGEAL DISEASE (LMD) FROM EPITHELIAL CARCINOMAS: FINAL RESULTS AND MOLECULAR ANALYSES WITH SINGLE CELL RNA SEQUENCING

Author

Pina, Yolanda, primary, Chen, Ann, additional, Arrington, John, additional, Macaulay, Robert, additional, Tran, Nam, additional, Liu, James, additional, Mokhtari, Sepideh, additional, Li, Jiannong, additional, Law, Vincent, additional, Sahebjam, Solmaz, additional, Ahmed, Kamran, additional, Creelan, Ben, additional, Gray, Jhanelle, additional, Evernden, Brittany, additional, Khushalani, Nikhil, additional, Czerniecki, Brian, additional, Smalley, Inna, additional, Vogelbaum, Michael, additional, Yu, Michael, additional, Smalley, Keiran, additional, and Forsyth, Peter, additional

Published
2023
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32. TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL

Author

Pina, Yolanda, primary, Chen, Ann, additional, Tran, Nam, additional, Etame, Arnold, additional, Liu, James, additional, Furlan, Andre Beer, additional, Mokhtari, Sepideh, additional, Peguero, Edwin, additional, Li, Jiannong, additional, Law, Vincent, additional, Khushalani, Nikhil, additional, Smalley, Inna, additional, Vogelbaum, Michael, additional, Yu, Michael, additional, Arrington, John, additional, Macaulay, Robert, additional, Tawbi, Hussein, additional, Smalley, Keiran, additional, and Forsyth, Peter, additional

Published
2023
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33. Key pathological features characterize minimal change disease-like IgA nephropathy

Author

Wang, Tsung-Yueh, primary, Chang, Fu-Pang, additional, Yang, An-Hang, additional, Ka, Shuk-Man, additional, Chen, Ann, additional, Hsieh, Jyh-Tong, additional, Chen, Fan-Yu, additional, Lee, Tsung-Lun, additional, Tseng, Po-Yu, additional, Tsai, Ming-Tsun, additional, Li, Szu-Yuan, additional, Yang, Chih-Yu, additional, Chen, Jinn-Yang, additional, Lin, Chih-Ching, additional, and Tarng, Der-Cherng, additional

Published
2023
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34. Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes

Author

Karapetyan, Lilit, primary, AbuShukair, Hassan M., additional, Li, Aofei, additional, Knight, Andrew, additional, Al Bzour, Ayah Nedal, additional, MacFawn, Ian P., additional, Thompson, Zachary J., additional, Chen, Ann, additional, Yang, Xi, additional, Dadey, Rebekah, additional, Karunamurthy, Arivarasan, additional, De Stefano, Danielle Vargas, additional, Sander, Cindy, additional, Kunning, Sheryl R., additional, Najjar, Yana G., additional, Davar, Diwakar, additional, Luke, Jason J., additional, Gooding, William, additional, Bruno, Tullia C., additional, Kirkwood, John M., additional, and Storkus, Walter J., additional

Published
2023
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35. Phase 1B study of avelumab and whole brain radiotherapy (WBRT) in patients with leptomeningeal disease (LMD) from epithelial carcinomas: Final results and molecular analyses with single cell RNA sequencing.

Author

Pina, Yolanda, primary, Chen, Ann, additional, Arrington, John, additional, Macaulay, Robert J, additional, Tran, Nam D., additional, Liu, James K, additional, Mokhtari, Sepideh, additional, Li, Jiannong, additional, Law, Vincent, additional, Sahebjam, Solmaz, additional, Ahmed, Kamran A., additional, Creelan, Ben C., additional, Gray, Jhanelle Elaine, additional, Evernden, Brittany, additional, Khushalani, Nikhil I., additional, Smalley, Inna, additional, Vogelbaum, Michael A., additional, Yu, Michael, additional, Smalley, Keiran, additional, and Forsyth, Peter A. J., additional

Published
2023
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43. Abstract 1192: Branched-chain keto acids exert an immune-suppressive and neurodegenerative microenvironment in CNS leptomeningeal lymphoma

Author

Khaled, Mariam Lotfy, primary, Wallace, Gerald, additional, Evernden, Brittany, additional, Chen, Zhihua, additional, Alhaddad, Hasan, additional, Ren, Yuan, additional, Ospina, Oscar, additional, Hall, Maclean, additional, Chen, Ann, additional, Robinson, Timothy J., additional, Koomen, John, additional, Pilon-thomas, Shari, additional, Forsyth, Peter, additional, and Smalley, Inna, additional

Published
2023
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45. Abstract 3606: HDAC8-mediated inhibition of EP300 drives a neural crest-like transcriptional state that increases melanoma brain metastasis

Author

Emmons, Michael, primary, Bennett, Richard, additional, Riva, Alberto, additional, Zhang, Chao, additional, Macaulay, Robert, additional, Dupéré-Richér, Daphne, additional, Fang, Bin, additional, Koomen, John, additional, Li, Jiannong, additional, Chen, Ann, additional, Seto, Edward, additional, Licht, Jonathan, additional, and Smalley, Keiran, additional

Published
2023
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47. Abstract 6065: Patterns of dysregulated coding and noncoding gene expression in high-grade serous ovarian carcinomas

Author

Reid, Brett M., primary, Chen, Ann, additional, Chen, Zhihua, additional, Karreth, Florian A., additional, Kanetsky, Peter, additional, Permuth, Jennifer B., additional, Saglam, Ozlen, additional, Teer, Jamie, additional, Yu, Xiaoqing, additional, Gayther, Simon, additional, Goode, Ellen, additional, Pharoah, Paul, additional, Sellers, Thomas A., additional, and Lawrenson, Kate, additional

Published
2023
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48. Supplementary Figure 1 from Tyrosine Phosphoproteomics Identifies Both Codrivers and Cotargeting Strategies for T790M-Related EGFR-TKI Resistance in Non–Small Cell Lung Cancer

Author

Yoshida, Takeshi, primary, Zhang, Guolin, primary, Smith, Matthew A., primary, Lopez, Alex S., primary, Bai, Yun, primary, Li, Jiannong, primary, Fang, Bin, primary, Koomen, John, primary, Rawal, Bhupendra, primary, Fisher, Kate J., primary, Chen, Ann Y., primary, Kitano, Michiko, primary, Morita, Yume, primary, Yamaguchi, Haruka, primary, Shibata, Kiyoko, primary, Okabe, Takafumi, primary, Okamoto, Isamu, primary, Nakagawa, Kazuhiko, primary, and Haura, Eric B., primary

Published
2023
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49. Supplementary Figure 3 from Tyrosine Phosphoproteomics Identifies Both Codrivers and Cotargeting Strategies for T790M-Related EGFR-TKI Resistance in Non–Small Cell Lung Cancer

Author

Yoshida, Takeshi, primary, Zhang, Guolin, primary, Smith, Matthew A., primary, Lopez, Alex S., primary, Bai, Yun, primary, Li, Jiannong, primary, Fang, Bin, primary, Koomen, John, primary, Rawal, Bhupendra, primary, Fisher, Kate J., primary, Chen, Ann Y., primary, Kitano, Michiko, primary, Morita, Yume, primary, Yamaguchi, Haruka, primary, Shibata, Kiyoko, primary, Okabe, Takafumi, primary, Okamoto, Isamu, primary, Nakagawa, Kazuhiko, primary, and Haura, Eric B., primary

Published
2023
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50. Supplementary Figure 2 from Tyrosine Phosphoproteomics Identifies Both Codrivers and Cotargeting Strategies for T790M-Related EGFR-TKI Resistance in Non–Small Cell Lung Cancer

Author

Yoshida, Takeshi, primary, Zhang, Guolin, primary, Smith, Matthew A., primary, Lopez, Alex S., primary, Bai, Yun, primary, Li, Jiannong, primary, Fang, Bin, primary, Koomen, John, primary, Rawal, Bhupendra, primary, Fisher, Kate J., primary, Chen, Ann Y., primary, Kitano, Michiko, primary, Morita, Yume, primary, Yamaguchi, Haruka, primary, Shibata, Kiyoko, primary, Okabe, Takafumi, primary, Okamoto, Isamu, primary, Nakagawa, Kazuhiko, primary, and Haura, Eric B., primary

Published
2023
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