ArticleScience advances2021
Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension.
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Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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19citing papers in PubMed, 1 pooled it
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.Science translational medicine · 2024Pooled it
- Dexamethasone prophylaxis protects from acute high-altitude illness by modifying the peripheral blood mononuclear cell inflammatory transcriptome.Bioscience reports · 2023Trial
- The Role of Piezo Ion Channels in Pulmonary Hypertension.Pulmonary circulation · 2026Review
- A multi-scale biological network framework for discovering MiRNA-Disease associations.Frontiers in bioinformatics · 2026Article
- Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.Science (New York, N.Y.) · 2025Article
- Post-transcriptional regulation of IFI16 promotes inflammatory endothelial pathophenotypes observed in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Precision Targeting of BET Proteins - Navigating Disease Pathways, Inhibitor Insights, and Shaping Therapeutic Frontiers: A Comprehensive Review.Current drug targets · 2025Review
- Genetics and precision genomics approaches to pulmonary hypertension.The European respiratory journal · 2024Review
- Post-transcriptional regulation of IFI16 promotes inflammatory endothelial pathophenotypes observed in pulmonary arterial hypertension.bioRxiv : the preprint server for biology · 2024Article
- CytoCellDB: a comprehensive resource for exploring extrachromosomal DNA in cancer cell lines.NAR cancer · 2024Article
- [Research progress on bioinformatics in pulmonary arterial hypertension].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Review
- Nuclear Control of Vascular Smooth Muscle Cell Plasticity during Vascular Remodeling.The American journal of pathology · 2024Review
- Bound Together: RNA Binding Protein Quaking, STAT3, and Pulmonary Vascular Remodeling.American journal of respiratory cell and molecular biology · 2023Article
- Differential responses of pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1.Respiratory research · 2023Article
- Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension.Circulation research · 2022Review
- Endothelial Senescence: A New Age in Pulmonary Hypertension.Circulation research · 2022Review
- Bioinformatic Exploration of Hub Genes and Potential Therapeutic Drugs for Endothelial Dysfunction in Hypoxic Pulmonary Hypertension.Computational and mathematical methods in medicine · 2022Article
- Mxi1-0 Promotes Hypoxic Pulmonary HypertensionFrontiers in genetics · 2022Article
- Pulmonary Arterial Hypertension: Emerging Principles of Precision Medicine across Basic Science to Clinical Practice.Reviews in cardiovascular medicine · 2022Article
Corrections and comments
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Authors and funding
31 authors.
Vinny NegiCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Jimin YangCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Gil SpeyerResearch Computing, Arizona State University, Tempe, AZ, USA.ORCID 0000-0001-5888-5209
Andres PulgarinCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0002-3144-171X
Adam HandenCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Jingsi ZhaoCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Yi Yin TaiCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0003-3674-0783
Ying TangCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Miranda K CulleyCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Qiujun YuCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Patricia ForsytheCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Anastasia GorelovaCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Annie M WatsonCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Yassmin Al AarajCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Taijyu SatohCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0002-1795-6872
Maryam Sharifi-SanjaniCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Arun RajaratnamCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
John SembratDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0003-4108-803X
Steeve ProvencherPulmonary Hypertension and Vascular Biology Research Group, Faculty of Medicine, Laval University, Quebec, QC, Canada.
Xianglin YinDepartment of Chemistry, Center for Cancer Research, Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA.
Sara O VargasDepartment of Pathology, Boston Children's Hospital, MA, USA.
Mauricio RojasDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Ohio State University College of Medicine, Columbus, OH, USA.ORCID 0000-0001-7340-4784
Sébastien BonnetPulmonary Hypertension and Vascular Biology Research Group, Faculty of Medicine, Laval University, Quebec, QC, Canada.ORCID 0000-0001-5753-1900
Stephanie TorrinoUniversité Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France.ORCID 0000-0002-8280-5907
Bridget K WagnerDepartment of Chemistry and Chemical Biology, Harvard University; Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-2629-361X
Stuart L SchreiberDepartment of Chemistry and Chemical Biology, Harvard University; Chemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-1922-7558
Mingji DaiDepartment of Chemistry, Center for Cancer Research, Institute for Drug Discovery, Purdue University, West Lafayette, IN, USA.ORCID 0000-0001-7956-6426
Thomas BerteroUniversité Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France.
Imad Al GhoulehCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0003-0386-5360
Seungchan KimPrairie View A&M Univ, Prairie View, TX, USA.ORCID 0000-0003-4183-4338
Stephen Y ChanCenter for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID 0000-0002-9520-7527
Funding
Targeting vulnerabilities of therapy-resistant cancer cell states with small moleculesU01CA217848 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2017 to 2021
$5.8MDefining the Complex Biology of the miR-130/301 Family in Pulmonary HypertensionR01HL124021 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHAN, STEPHEN Y · 2014 to 2025
$4.9MIron-Sulfur Deficiency as a Critical Pathogenic Cause of Pulmonary HypertensionR01HL122596 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHAN, STEPHEN Y · 2015 to 2024
$4.5MSystematic Development of Novel, Druggable Cancer TargetsU01CA168397 · NCI · TRANSLATIONAL GENOMICS RESEARCH INST · PI BERENS, MICHAEL E. · 2012 to 2016
$4.1MMolecular Drivers of Vascular Stiffness and Metabolic Dysfunction in HIV-Induced Pulmonary Arterial HypertensionR01HL138437 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHAN, STEPHEN Y, NORRIS, KAREN A · 2017 to 2020
$2.4MEndothelial Reprogramming in Pulmonary HypertensionR01HL148712 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AL GHOULEH, IMAD · 2019 to 2023
$1.9MComputational repurposing of chemotherapies for pulmonary hypertensionUH2TR002073 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHAN, STEPHEN Y · 2017 to 2018
$615kAdvanced High Resolution Rodent Ultrasound Imaging SystemS10OD023684 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIM, KANG · 2018 to 2018
$390kNCATS NIH HHS UH2 TR002073NCI NIH HHS U01 CA168397NCI NIH HHS U01 CA217848NHLBI NIH HHS R01 HL122596NHLBI NIH HHS R01 HL124021NHLBI NIH HHS R01 HL138437NHLBI NIH HHS R01 HL148712NIH HHS S10 OD023684
Abstract
Cancer therapies are being considered for treating rare noncancerous diseases like pulmonary hypertension (PH), but effective computational screening is lacking. Via transcriptomic differential dependency analyses leveraging parallels between cancer and PH, we mapped a landscape of cancer drug functions dependent upon rewiring of PH gene clusters. Bromodomain and extra-terminal motif (BET) protein inhibitors were predicted to rely upon several gene clusters inclusive of galectin-8 (LGALS8). Correspondingly, LGALS8 was found to mediate the BET inhibitor–dependent control of endothelial apoptosis, an essential role for PH in vivo. Separately, a piperlongumine analog’s actions were predicted to depend upon the iron-sulfur biogenesis gene ISCU. Correspondingly, the analog was found to inhibit ISCU glutathionylation, rescuing oxidative metabolism, decreasing endothelial apoptosis, and improving PH. Thus, we identified crucial drug-gene axes central to endothelial dysfunction and therapeutic priorities for PH. These results establish a wide-ranging, network dependency platform to redefine cancer drugs for use in noncancerous conditions.
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