My laboratory focuses on lung repair and pulmonary fibrosis. We are currently investigating molecular mechanisms implicated in the differentiation of lung fibroblasts into myofibroblasts during lung fibrosis, with particular emphasis on transcriptional and epigenetic mechanisms driving persistent fibrogenesis in idiopathic pulmonary fibrosis (IPF). We have recently discovered that in the lung, myofibroblast differentiation occurs through the engagement of chromatin modifier enzymes and epigenetic readers. We found that the histone methyltransferase G9a and the epigenetic reader CBX5 play a critical role in lung fibroblast activation, and that targeting these epigenetic modifiers enhanced mitochondrial function, blocked ECM protein secretion, and attenuated lung fibrogenesis.
In addition, my laboratory is interested in investigating the impact of aging on the development of pulmonary fibrosis. We have recently discovered that the endothelium of aged mouse lungs is dysfunctional and this abnormality leads to capillary loss and persistent lung fibrosis following injury. Using a multi-omics approach (RNA-seq, ATAC-seq, and scRNA-seq) we have identified transcriptional programs in lung endothelial cells orchestrating lung vascular repair and whose abnormal activation with aging leads to persistent lung fibrosis.
Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences
Epigenetic gene repression in pulmonary fibrosis
09/18/2019 - 06/30/2023 (PI)NIH/National Heart, Lung, and Blood Institute5R01HL142596-04
Publications listed below are automatically derived from MEDLINE/PubMed and other
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Showing 10 of 50 results.
Ligresti G, Pham TX, Sanders YY. Circular RNA Methylation: A New Twist in Lung Fibrosis. Am J Respir Cell Mol Biol. 2022 May; 66(5):471-472.View Related Profiles. PMID: 35238732
Pham TX, Lee J, Guan J, Caporarello N, Meridew JA, Jones DL, Tan Q, Huang SK, Tschumperlin DJ, Ligresti G. Transcriptional analysis of lung fibroblasts identifies PIM1 signaling as a driver of aging-associated persistent fibrosis. JCI Insight. 2022 Mar 22; 7(6).View Related Profiles. PMID: 35167499; PMCID: PMC8986080; DOI: 10.1172/jci.insight.153672;
Ring NAR, Volpe MC, Stepišnik T, Mamolo MG, Panov P, Kocev D, Vodret S, Fortuna S, Calabretti A, Rehman M, Colliva A, Marchesan P, Camparini L, Marcuzzo T, Bussani R, Scarabellotto S, Confalonieri M, Pham TX, Ligresti G, Caporarello N, Loffredo FS, Zampieri D, Džeroski S, Zacchigna S. Wet-dry-wet drug screen leads to the synthesis of TS1, a novel compound reversing lung fibrosis through inhibition of myofibroblast differentiation. Cell Death Dis. 2021 12 17; 13(1):2.View Related Profiles. PMID: 34916483; PMCID: PMC8677786; DOI: 10.1038/s41419-021-04439-4;
Nicosia RF, Ligresti G, Caporarello N, Akilesh S, Ribatti D. COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury. Am J Pathol. 2021 08; 191(8):1374-1384. PMID: 34033751; PMCID: PMC8141344; DOI: 10.1016/j.ajpath.2021.05.007;
Jones DL, Meridew JA, Link PA, Ducharme MT, Lydon KL, Choi KM, Caporarello N, Tan Q, Diaz Espinosa AM, Xiong Y, Lee JH, Ye Z, Yan H, Ordog T, Ligresti G, Varelas X, Tschumperlin DJ. ZNF416 is a pivotal transcriptional regulator of fibroblast mechanoactivation. J Cell Biol. 2021 05 03; 220(5).View Related Profiles. PMID: 33625469; PMCID: PMC7918622; DOI: 10.1083/jcb.202007152;
Ji S, Traini C, Mischopoulou M, Gibbons SJ, Ligresti G, Faussone-Pellegrini MS, Sha L, Farrugia G, Vannucchi MG, Cipriani G. Muscularis macrophages establish cell-to-cell contacts with telocytes/PDGFRa-positive cells and smooth muscle cells in the human and mouse gastrointestinal tract. Neurogastroenterol Motil. 2021 03; 33(3):e13993. PMID: 33020982; PMCID: PMC7902307; DOI: 10.1111/nmo.13993;
Vivarelli S, Falzone L, Ligresti G, Candido S, Garozzo A, Magro GG, Bonavida B, Libra M. Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets. Int J Mol Sci. 2020 Sep 03; 21(17). PMID: 32899428; PMCID: PMC7504013; DOI: 10.3390/ijms21176446;
Caporarello N, Meridew JA, Aravamudhan A, Jones DL, Austin SA, Pham TX, Haak AJ, Moo Choi K, Tan Q, Haresi A, Huang SK, Katusic ZS, Tschumperlin DJ, Ligresti G. Vascular dysfunction in aged mice contributes to persistent lung fibrosis. Aging Cell. 2020 08; 19(8):e13196.View Related Profiles. PMID: 32691484; PMCID: PMC7431829; DOI: 10.1111/acel.13196;
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