Article
Biochemistry & Molecular Biology
Emily R. Theisen, Julia Selich-Anderson, Kyle R. Miller, Jason M. Tanner, Cenny Taslim, Kathleen I. Pishas, Sunil Sharma, Stephen L. Lessnick
Summary: Pediatric cancers often have quiet mutational landscapes, instead characterized by single driver events like chromatin regulator mutations or oncohistone expression. The fusion protein EWS/FLI in Ewing sarcoma reshapes enhancer landscape through collaboration with LSD1, impacting widespread gene regulation throughout the genome. The dynamic rearrangement of LSD1 by EWS/FLI plays a crucial role in gene activation and establishment of super-enhancers, ultimately influencing the enhancer landscape in Ewing sarcoma.
Article
Oncology
April A. Apfelbaum, Feinan Wu, Allegra G. Hawkins, Brian Magnuson, Jennifer A. Jime, Sean D. Taylor, Emma D. Wrenn, Olivia Waltner, Elise R. Pfaltzgraff, Jane Y. Song, Cody Hall, Deneen M. Wellik, Mats Ljungman, Scott N. Furlan, Russell J. H. Ryan, Jay F. Sarthy, Elizabeth R. Lawlor
Summary: This study reveals the regulatory role of HOXD13 in EWS::FLI1 transcriptional activity and its impact on the transition of Ewing sarcoma cells towards a mesenchymal state. The findings provide important insights into the progression mechanism of Ewing sarcoma.
CLINICAL CANCER RESEARCH
(2022)
Article
Genetics & Heredity
Runzhi Huang, Dan Huang, Siqiao Wang, Shuyuan Xian, Yifan Liu, Minghao Jin, Xinkun Zhang, Shaofeng Chen, Xi Yue, Wei Zhang, Jianyu Lu, Huizhen Liu, Zongqiang Huang, Hao Zhang, Huabin Yin
Summary: Through systematic bioinformatics analysis, this study revealed the key regulatory network of Ewing sarcoma, which includes DEeRNAs, DETGs, DETFs, immune cells, immune gene sets, and hallmarks of cancer. Additionally, potential small molecules targeting Ewing sarcoma were also identified. The results of this study indicate that PHLDA1 plays a crucial role in the tumorigenesis and progression of Ewing sarcoma.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Miwa Watanabe, Hiromichi Kosaka, Masamori Sugawara, Michihiro Maemoto, Yoko Ono, Takeshi Uemori, Ryota Shizu, Kouichi Yoshinari
Summary: The DHODH inhibitor K-234 and its derivatives can inhibit the function of DAX1 and EWS-FLI1 in Ewing's sarcoma, suggesting their potential as therapeutic agents for Ewing's sarcoma patients.
Article
Multidisciplinary Sciences
Takao Kitagawa, Daiki Kobayashi, Byron Baron, Hajime Okita, Tatsuo Miyamoto, Rie Takai, Durga Paudel, Tohru Ohta, Yoichi Asaoka, Masayuki Tokunaga, Koji Nakagawa, Makoto Furutani-Seiki, Norie Araki, Yasuhiro Kuramitsu, Masanobu Kobayashi
Summary: It has been discovered that AHDC1 is a proximal protein of EWS-ETS fusion proteins and supports cell growth through interaction with EWS-FLI1. Knockdown of AHDC1 reduces cell growth and transcriptional activity of EWS-FLI1, as well as the levels of interacting proteins BRD4 and BRG1.
Article
Biochemistry & Molecular Biology
Daniel J. Garcia-Dominguez, Nabil Hajji, Sara Sanchez-Molina, Elisabet Figuerola-Bou, Rocio M. de Pablos, Ana M. Espinosa-Oliva, Eduardo Andres-Leon, Laura Carmen Terron-Camero, Rocio Flores-Campos, Guillem Pascual-Pasto, Maria Jose Robles, Angel M. Carcaboso, Jaume Mora, Enrique de Alava, Lourdes Hontecillas-Prieto, Isidro Machado, Antonio Llombart-Bosch, Giovanna Magagnoli, Katia Scotlandi
Summary: The study reveals that HDAC6 plays a regulatory role in EWS, and selective inhibition of HDAC6 can reduce the oncogenic functions of EWSR1-FLI1. High expression of HDAC6 is associated with poor prognosis in EWS patients, and a combination treatment of HDAC6 and doxorubicin significantly inhibits tumor growth in EWS models.
Article
Cell Biology
Fatu Badiane Markey, Brigette Romero, Vijay Parashar, Mona Batish
Summary: Research has identified NKX2.2 as a co-regulator of STEAP1 expression in ES, interacting with EWSFLI1, which holds potential as a new target for therapeutic interventions for ES.
Article
Oncology
Florian Perner, Tina M. Schnoeder, Yijun Xiong, Ashok Kumar Jayavelu, Nomusa Mashamba, Nuria Tubio Santamaria, Nicolas Huber, Kristina Todorova, Charles Hatton, Birgit Perner, Theresa Eifert, Ciara Murphy, Maximilian Hartmann, Jessica I. Hoell, Nicolas Schroeder, Sabine Brandt, Andreas Hochhaus, Peter R. Mertens, Matthias Mann, Scott A. Armstrong, Anna Mandinova, Florian H. Heidel
Summary: The study reveals the essential role of YBX1 in AML, with its inactivation reducing the competitive advantage of malignant cells, inhibiting leukemia cell proliferation, and playing a key role in oncogenic protein expression. This provides a new perspective for the treatment of AML.
Review
Pathology
Maria Antonietta Fedeli, Vincenzo Marras, Antonella Maria Fara, Angelo Deiana, Renato Lobrano, Antonio Cossu, Panagiotis Paliogiannis
Summary: A systematic review of primary pulmonary Ewing sarcoma (PES) cases published in the last decade on PubMed was conducted to provide a comprehensive understanding of the clinical, pathological, therapeutic, and prognostic characteristics. The review included 42 articles reporting on 50 cases. The majority of patients were males, with an average age of diagnosis at 30.5 years. Common clinical manifestations at diagnosis were dyspnea, cough, and chest pain. Immunohistochemistry showed staining for CD99 and vimentin. The disease was often locally advanced and treated with surgery, chemotherapy, and radiation therapy. 40% of patients had died at the time of publication, with a median survival of 11.5 months. Only 8.3% of survivors were free from disease at 48 months after diagnosis.
ANNALS OF DIAGNOSTIC PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Megann A. Boone, Cenny Taslim, Jesse C. Crow, Julia Selich-Anderson, Andrea K. Byrum, Iftekhar A. Showpnil, Benjamin D. Sunkel, Meng Wang, Benjamin Z. Stanton, Emily R. Theisen, Stephen L. Lessnick
Summary: Ewing sarcoma, a type of bone cancer, is caused by the fusion protein EWS/FLI. Research has shown that different domains of the FLI protein play critical roles in the oncogenic function of EWS/FLI, with the ETS domain being essential for DNA-binding and chromatin accessibility, and an additional alpha-helix downstream of the ETS domain necessary for full transcriptional regulation and oncogenesis.
Article
Oncology
Guillermo Flores, Patrick J. Grohar
Summary: EWS/FLI is the defining mutation of Ewing sarcoma, driving malignant transformation. However, as a transcription factor, it presents a challenging drug target due to its involvement in a complex protein network. While this complexity poses difficulty for developing highly specific inhibitors, it also offers numerous therapeutic opportunities.
JOURNAL OF BONE ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mingli Li, Chun-Wei Chen
Summary: This review discusses the epigenetic and transcriptional alterations in Ewing sarcoma and summarizes the relevant screening studies conducted to develop novel therapies.
Article
Biochemistry & Molecular Biology
Jinwu Deng, Weinan Sun, Boyang Zhang, Simin Sun, Linjie Xia, Yuhuan Miao, Liangrong He, Keith Lindsey, Xiyan Yang, Xianlong Zhang
Summary: The basic helix-loop-helix transcription factor GhTCE1 and its interacting partners play a crucial role in the regulation of early cell fate transition and development in in vitro dedifferentiation of cotton cells. The network involves reactive oxygen species and lipid transfer proteins, which are important for maintaining reactive oxygen species homeostasis and cell wall metabolism.
Article
Dermatology
Jin Wook Lee, Dong Min Kim, Ji Yeoun Lee, Tae Young Yoon
Summary: Primary cutaneous extraskeletal Ewing sarcoma is a rare tumor that usually occurs on the trunk or extremities of young adults. We report a case of this tumor, including the result of genetic testing.
ANNALS OF DERMATOLOGY
(2022)
Article
Biophysics
Courtney N. Johnson, Xiaoping Xu, Stephen P. Holloway, David S. Libich
Summary: The RNA-binding protein EWS is involved in transcription regulation and RNA splicing. It belongs to the FET family of RNA binding proteins, which have an intrinsically disordered N-terminal domain. The fusion of the low-complexity domain of FET family proteins with a DNA-binding domain of transcription factors is oncogenic in certain leukemias and sarcomas. The exact mechanism of how the disordered domain contributes to abnormal DNA binding and transcription is unclear. This study describes the purification and resonance assignments of the amino terminal domain of EWS, which is common to all EWS-fusions found in Ewing sarcoma. These assignments provide insights into the contribution of the low-complexity domain to the abnormal functions of oncogenic fusion proteins.
BIOMOLECULAR NMR ASSIGNMENTS
(2022)
Article
Ophthalmology
Leah A. Owen, Joshua Ford, Nick Mamalis, Robert Hoffman, Mark Mifflin
Article
Ophthalmology
Kyle D. MacLean, Scott C. Cole, Joshua R. Ford, Leah Owen, Nick Mamalis, Bhupendra C. K. Patel
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
(2016)
Review
Biochemistry & Molecular Biology
Margaret M. DeAngelis, Leah A. Owen, Margaux A. Morrison, Denise J. Morgan, Mingyao Li, Akbar Shakoor, Albert Vitale, Sudha Iyengar, Dwight Stambolian, Ivana K. Kim, Lindsay A. Farrer
HUMAN MOLECULAR GENETICS
(2017)
Article
Ophthalmology
Julia M. Byrd, Marielle P. Young, Wei Liu, Yue Zhang, David B. Tate, Alan S. Crandall, Leah A. Owen
JOURNAL OF CATARACT AND REFRACTIVE SURGERY
(2018)
Article
Ophthalmology
Joshua R. Ford, Liliana Werner, Leah Owen, Shail A. Vasavada, Alan Crandall
JOURNAL OF CATARACT AND REFRACTIVE SURGERY
(2014)
Article
Multidisciplinary Sciences
Leah A. Owen, Margaux A. Morrison, Robert O. Hoffman, Bradley A. Yoder, Margaret M. DeAngelis
Article
Genetics & Heredity
Lloyd B. Williams, Asif Javed, Amin Sabri, Denise J. Morgan, Chad D. Huff, John R. Grigg, Xiu Ting Heng, Alexis J. Khng, Iris H. I. M. Hollink, Margaux A. Morrison, Leah A. Owen, Katherine Anderson, Krista Kinard, Rebecca Greenlees, Danica Novacic, H. Nida Sen, Wadih M. Zein, George M. Rodgers, Albert T. Vitale, Neena B. Haider, Axel M. Hillmer, Pauline C. Ng, Shankaracharya, Anson Cheng, Linda Zheng, Mark C. Gillies, Marjon van Slegtenhorst, P. Martin van Hagen, Tom O. A. R. Missotten, Gary L. Farley, Michael Polo, James Malatack, Julie Curtin, Frank Martin, Susan Arbuckle, Stephen Alexander, Megan Chircop, Sonia Davila, Kathleen B. Digre, Robyn Jamieson, Margaret M. DeAngelis
GENETICS IN MEDICINE
(2019)
Article
Biochemistry & Molecular Biology
Yara A. Samra, Dina Kira, Pragya Rajpurohit, Riyaz Mohamed, Leah A. Owen, Akbar Shakoor, Ivana K. Kim, Margaret M. DeAngelis, Nader Sheibani, Mohamed Al-Shabrawey, Amany Tawfik
Summary: The study suggests that the activation of NMDAR in the retina pigment epithelium may be a mechanism for AMD induced by HHcy. Inhibition of NMDAR could be a promising therapeutic target for AMD, as knocking down RPE NMDAR improved retinal structure and CNV in mice with AMD-like features induced by HHcy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Patrice M. Hicks, Elizabeth Au, William Self, Benjamin Haaland, Michael Feehan, Leah A. Owen, Adam Siedlecki, Elizabeth Nuttall, Deborah Harrison, Andrew L. Reynolds, John H. Lillvis, Sandra Sieminski, Julia P. Shulman, Margarita Barnoya, Juan Jose Noguera Prera, Orlando Gonzalez, Maureen A. Murtaugh, Lloyd B. Williams, Michael H. Farkas, Alan S. Crandall, Margaret M. DeAngelis
Summary: The study reveals unique risk factors for blinding eye diseases within the Mayan population of Guatemala, providing insights for targeted screening strategies. Cataracts and pseudoexfoliation syndrome are the most prevalent eye conditions, associated with advanced age and more common in districts with limited resources.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Medicine, General & Internal
Michael Feehan, Leah A. Owen, Ian M. McKinnon, Margaret M. DeAngelis
Summary: The use of AI and ML in clinical care shows promise in improving patient health outcomes and reducing health disparities, but inherent biases and potential risks of harm need to be addressed. Developing multi-modal workflows to minimize limitations and considering rapidly evolving AI technologies, expanding data sources, and changing regulatory landscapes are crucial in enhancing clinical decision making and reducing health inequity.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Charles Zhang, Leah A. Owen, John H. Lillvis, Sarah X. Zhang, Ivana K. Kim, Margaret M. DeAngelis
Summary: Age-related macular degeneration (AMD) is a leading cause of blindness in the aging population. Specific prognostic tools and effective therapies for intermediate and advanced stages of AMD are needed. Recent clinical trials have shown promising results with anti-C5 and anti-C3 agents in slowing the growth of advanced AMD, but they may increase the incidence of wet AMD. Further research on the role of non-coding RNAs (ncRNAs) in AMD is crucial for developing biomarkers and therapeutic targets.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Pathology
Leah A. Owen, Charles Zhang, Kinsey Shirer, Lara Carroll, Blair Wood, Kathryn Szczotka, Colette Cornia, Christopher Stubben, Camille Fung, Christian C. Yost, Lakshmi D. Katikaneni, Margaret M. DeAngelis, Jessica Comstock
Summary: This study identifies a protective association between acute placental inflammation and the development of retinopathy of prematurity (ROP) in preterm infants. It also identifies novel mechanisms that may contribute to this protective association. These findings provide new insights into the postnatal risk associations in preterm infants.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julie L. L. Barr, Michael Feehan, Casey Tak, Leah A. A. Owen, Robert C. C. Finley, Parker A. A. Cromwell, John H. H. Lillvis, Patrice M. M. Hicks, Elizabeth Au, Michael H. H. Farkas, Asher Weiner, Andrew L. L. Reynolds, Sandra E. F. Sieminski, Richard M. M. Sherva, Mark A. A. Munger, Murray H. H. Brilliant, Margaret M. M. DeAngelis
Summary: Glaucoma is a major cause of irreversible blindness, affecting 76 million people worldwide. Non-adherence to glaucoma medications is a significant problem despite research and patient education efforts. This study aimed to determine the genetic component behind glaucoma medication non-adherence and identified several genes and variants associated with non-adherence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Treefa Shwani, Charles Zhang, Leah A. Owen, Akbar Shakoor, Albert T. Vitale, John H. Lillvis, Julie L. Barr, Parker Cromwell, Robert Finley, Nadine Husami, Elizabeth Au, Rylee A. Zavala, Elijah C. Graves, Sarah X. Zhang, Michael H. Farkas, David A. Ammar, Karen M. Allison, Amany Tawfik, Richard M. Sherva, Mingyao Li, Dwight Stambolian, Ivana K. Kim, Lindsay A. Farrer, Margaret M. DeAngelis
Summary: Age-related macular degeneration (AMD) is a debilitating eye disease that can lead to blindness. In this study, researchers identified differentially expressed and spliced genes in the macular retina affected by AMD. They also found associations between AMD risk loci and gene expression changes. The study provides valuable insights into the genetic mechanisms underlying AMD, which may have implications for the development of diagnostics and therapies.
Article
Ophthalmology
Leah A. Owen, Margaux A. Morrison, Jeeyun Ahn, Se Joon Woo, Hajime Sato, Rosann Robinson, Denise J. Morgan, Fani Zacharaki, Marina Simeonova, Hironori Uehara, Usha Chakravarthy, Ruth E. Hogg, Balamurali K. Ambati, Maria Kotoula, Wolfgang Baehr, Neena B. Haider, Giuliana Silvestri, Joan W. Miller, Evangelia E. Tsironi, Lindsay A. Farrer, Ivana K. Kim, Kyu Hyung Park, Margaret M. DeAngelis
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2014)