Epigenetics in Human Health and Disease
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Head of Laboratory
Professor Sam El-Ostasam.elosta@unimelb.edu.au; sam.el-osta@baker.edu.au
+61 3 8532 1389
Research Overview
It is increasingly appreciated that gene-environment interactions are key areas of interest, particularly as they pertain to human health and disease. These involve epigenetic pathways including a range of biochemical modifications of chromatin (including DNA methylation). The central focus of the research team is to investigate the mechanisms by which specific epigenetic changes including chromatin modifications serve to integrate the transcriptional responses to distinct signaling pathways. The rapid rate of progress over the past five years and the series of discoveries that we and others have contributed in the field concerning epigenetic modification and gene regulation reflect unheralded advances in understanding human development and disease.
We are interested in characterising the functional roles of specific components critical in gene regulation and examining the link to human disease using genetic, epigenomic and molecular approaches. The group led by Professor El-Osta is interested in understanding the roles of specific transcriptional components in the regulation of metabolic memory and cardiac disease and further extending our understanding of gene silencing events associated with genomic methylation in preclinical models and human populations. The focus of the laboratory is to provide fundamental insights into the mechanisms by which epigenetic changes and associated chromatin modifications control genes implicated in human health and disease.
Our investigation of the molecular mechanisms of gene regulation by specific repressor and co-activator complexes using vascular endothelial and cardiac cells as well as the brain, has led to a range of novel mechanistic insights into the biology of epigenetic changes mediating critical transcriptional changes in models of endothelial dysfunction, vascular disease and in utero programming. Professor El-Osta and his team have contributed to understanding the molecular mechanisms whereby epigenetic changes exert positive and negative transcriptional functions in specific model systems. His team explores the relationship between different classes of co-repressor and activator complexes and the regulation of chromatin remodelling events in maintaining gene expression implicated in disease.
Staff
Postdoctoral Scientists
Dr Tom Karagiannis
Dr Ishant Khurana
Dr Harikrishnan Kaipananickal
Dr Keith Al-Hasani
Dr Jun Okabe
Dr Scott Maxwell
Dr Ram Abou Zaki MD
Dr Caroline Froerup
Scientific Staff
Johnny Asaf
PhD Students
Safiya Naina Marikar
Julia Liang
MSc Students
Sorine Birkelund
Lyana Ang
International Interns
Julie Kinnberg
Charlotte Kjerulff
Collaborators
Dr Thomas Loudavaris, St Vincent’s Institute, Melbourne, Australia.
Prof Alex Brown, Indigenous Genomics, Australian National University, Telethon Kids Institute, Australia.
Prof Mark Cooper, Department of Diabetes, Monash University, Melbourne, Australia.
Prof Peter Rossing, Steno Diabetes Centre Copenhagen, Denmark.
Dr Frederik Persson, Steno Diabetes Centre Copenhagen, Denmark.
Prof Eske Willerslev, Lundbeck Foundation GeoGenetics Centre and Cambridge, UK.
Prof Ronald C.W. Ma, Hong Kong Institute of Diabetes and Obesity, Hong Kong.
Prof Juliana Chan, Hong Kong Institute of Diabetes and Obesity, Hong Kong.
Prof. Assaad A. Eid, American University of Beirut, Lebanon.
A/Prof Charumathi, Duke-NUS Medical School, Singapore.
Prof Roger Foo, NUS Cardiovascular Research Institute, Singapore.
Dr Charumathi Sabanayagam, Eye Research Institute, Singapore.
Dr. Yotsapon Thewjitcharoen, Theptarin Hospital, Bangkok, Thailand.
Prof Himathongkam Thep, Theptarin Hospital, Bangkok, Thailand.
Prof. Per-Henrik Groop, Biomedicum, Helsinki, Finland.
Dr. Katja Kobow, Universitätsklinikum Erlangen, Erlangen, Germany.
Prof. Ingmar Blumcke, University Hospitals Erlangen, Erlangen, Germany.
Prof. Imad M Najm, Cleveland Clinic Epilepsy Center, Cleveland, USA.
Prof. Francesco Paneni, University Heart Center, Zürich, Switzerland.
Dr. Maria Cristina Vinci, Centro Cardiologico Monzino, Milano, Italy.
Funding
National Health and Medical Research Council (NHMRC)
Australia Research Council (ARC)
JDRF
Research Opportunities
This research project is available to PhD students, Masters by Research, Master of Biomedical Science, Post Doctor Researchers to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.
Research Outcomes
Publications
1. Vinci MC, Costantino S, Damiano G, Rurali E, Rinaldi R, Vigorelli V, Sforza A, Carulli E, Pirola S, Mastroiacovo G, et al. Persistent epigenetic signals propel a senescence-associated secretory phenotype and trained innate immunity in CD34(+) hematopoietic stem cells from diabetic patients. Cardiovasc Diabetol. 2024;23:107. doi: 10.1186/s12933-024-02195-1
2. Sourris KC, Ding Y, Maxwell SS, Al-Sharea A, Kantharidis P, Mohan M, Rosado CJ, Penfold SA, Haase C, Xu Y, et al. Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products-induced inflammation. Kidney Int. 2024;105:132-149. doi: 10.1016/j.kint.2023.09.029
3. Karagiannis TC, Orlowski C, Ververis K, Pitsillou E, Sarila G, Keating ST, Foong LJ, Fabris S, Ngo-Nguyen C, Malik N, et al. gammaH2AX in mouse embryonic stem cells: Distribution during differentiation and following gamma-irradiation. Cells Dev. 2024;177:203882. doi: 10.1016/j.cdev.2023.203882
4. Al-Hasani K, Marikar SN, Kaipananickal H, Maxwell S, Okabe J, Khurana I, Karagiannis T, Liang JJ, Mariana L, Loudovaris T, et al. EZH2 inhibitors promote beta-like cell regeneration in young and adult type 1 diabetes donors. Signal Transduct Target Ther. 2024;9:2. doi: 10.1038/s41392-023-01707-x
5. Sangeetha Menon A, Subasic de Azevedo I, Choong K, Bhatnagar D, Wang C, Sluka P, Chisholm DR, Pasic P, Thissen H, Sama G, et al. Advances in Design and Development of Lumi-Solve: A Novel Drug-Eluting Photo-Angioplasty Device. Cardiovasc Eng Technol. 2023;14:605-614. doi: 10.1007/s13239-023-00668-0
6. Pitsillou E, Logothetis ANO, Liang JJ, El-Osta A, Hung A, AbuMaziad AS, Karagiannis TC. Identification of Potential Modulators of a Pathogenic G Protein-Gated Inwardly Rectifying K(+) Channel 4 Mutant: In Silico Investigation in the Context of Drug Discovery for Hypertension. Molecules. 2023;28. doi: 10.3390/molecules28247946
7. Perez S, Lavi-Itzkovitz A, Gidoni M, Domovitz T, Dabour R, Khurana I, Davidovich A, Tobar A, Livoff A, Solomonov E, et al. High-Resolution Genomic Profiling of Liver Cancer Links Etiology With Mutation and Epigenetic Signatures. Cell Mol Gastroenterol Hepatol. 2023;16:63-81. doi: 10.1016/j.jcmgh.2023.03.004
8. Naina Marikar S, Al-Hasani K, Khurana I, Kaipananickal H, Okabe J, Maxwell S, El-Osta A. Pharmacological inhibition of human EZH2 can influence a regenerative beta-like cell capacity with in vitro insulin release in pancreatic ductal cells. Clin Epigenetics. 2023;15:101. doi: 10.1186/s13148-023-01491-z
9. Khurana I, Kaipananickal H, Maxwell S, Birkelund S, Syreeni A, Forsblom C, Okabe J, Ziemann M, Kaspi A, Rafehi H, et al. Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes. J Clin Invest. 2023;133. doi: 10.1172/JCI160959
10. Khurana I, Howard NJ, Maxwell S, Du Preez A, Kaipananickal H, Breen J, Buckberry S, Okabe J, Al-Hasani K, Nakasatien S, et al. Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2023;204:110918. doi: 10.1016/j.diabres.2023.110918
11. Keating ST, El-Osta A. Metaboloepigenetics in cancer, immunity, and cardiovascular disease. Cardiovasc Res. 2023;119:357-370. doi: 10.1093/cvr/cvac058
12. Karagiannis TC, Wall M, Ververis K, Pitsillou E, Tortorella SM, Wood PA, Rafehi H, Khurana I, Maxwell SS, Hung A, et al. Characterization of K562 cells: uncovering novel chromosomes, assessing transferrin receptor expression, and probing pharmacological therapies. Cell Mol Life Sci. 2023;80:248. doi: 10.1007/s00018-023-04905-6
13. El-Osta A. Transcriptional Control of Endothelial Senescence and Vascular Repair. Circ Res. 2023;133:858-860. doi: 10.1161/CIRCRESAHA.123.323716
14. Thomas JL, Bruzzone R, El-Osta A, Claessens F, Ruysschaert JM, Wilson DM, 3rd. Tribute to Klaus Eichmann, Editor-in-Chief of Cellular and Molecular Life Sciences. Cell Mol Life Sci. 2022;79:529. doi: 10.1007/s00018-022-04532-7
15. Thewjitcharoen Y, Wanothayaroj E, Nakasatien S, Krittiyawong S, Khurana I, El-Osta A, Himathongkam T. Diabetes mellitus and insulin resistance associated with Kabuki syndrome-A case report and literature review. Clin Case Rep. 2022;10:e05736. doi: 10.1002/ccr3.5736
16. Shi Z, Tuomilehto J, Kronfeld-Schor N, Alberti G, Stern N, El-Osta A, Chai Z, Bilu C, Einat H, Zimmet P. The Circadian Syndrome Is a Significant and Stronger Predictor for Cardiovascular Disease than the Metabolic Syndrome-The NHANES Survey during 2005-2016. Nutrients. 2022;14. doi: 10.3390/nu14245317
17. Royce SG, Licciardi PV, Beh RC, Bourke JE, Donovan C, Hung A, Khurana I, Liang JJ, Maxwell S, Mazarakis N, et al. Sulforaphane prevents and reverses allergic airways disease in mice via anti-inflammatory, antioxidant, and epigenetic mechanisms. Cell Mol Life Sci. 2022;79:579. doi: 10.1007/s00018-022-04609-3
18. Pinzon Cortes JA, El-Osta A, Fontemaggi G, Delihas N, Miyazaki K, Goel A, Brazane M, Carre C, Dama P, Bayraktar S, et al. The Non-Coding RNA Journal Club: Highlights on Recent Papers-10. Noncoding RNA. 2022;8. doi: 10.3390/ncrna8010003
19. Noureldein M, Nawfal R, Bitar S, Maxwell SS, Khurana I, Kassouf HK, Khuri FR, El-Osta A, Eid AA. Intestinal microbiota regulates diabetes and cancer progression by IL-1beta and NOX4 dependent signaling cascades. Cell Mol Life Sci. 2022;79:502. doi: 10.1007/s00018-022-04485-x
20. Najm I, Lal D, Alonso Vanegas M, Cendes F, Lopes-Cendes I, Palmini A, Paglioli E, Sarnat HB, Walsh CA, Wiebe S, et al. The ILAE consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission. Epilepsia. 2022;63:1899-1919. doi: 10.1111/epi.17301
21. Mathiyalagan P, Martelotto LG, Ounzain S, El-Osta A, Uchida S. Editorial: RNA-chromatin interactions: Biology, mechanism, disease and therapeutics. Front Genet. 2022;13:1069427. doi: 10.3389/fgene.2022.1069427
22. Marikar SN, El-Osta A, Johnston A, Such G, Al-Hasani K. Microencapsulation-based cell therapies. Cell Mol Life Sci. 2022;79:351. doi: 10.1007/s00018-022-04369-0
23. El-Osta A. Distinguishing transgender DNA methylation. Clin Epigenetics. 2022;14:25. doi: 10.1186/s13148-022-01238-2
24. Al-Hasani K, Khurana I, Mariana L, Loudovaris T, Maxwell S, Harikrishnan KN, Okabe J, Cooper ME, El-Osta A. Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor. Signal Transduct Target Ther. 2022;7:248. doi: 10.1038/s41392-022-01034-7
25. Watt KI, Henstridge DC, Ziemann M, Sim CB, Montgomery MK, Samocha-Bonet D, Parker BL, Dodd GT, Bond ST, Salmi TM, et al. Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease. Nat Commun. 2021;12:2887. doi: 10.1038/s41467-021-23240-7
26. Thewjitcharoen Y, Wanothayaroj E, Jaita H, Nakasatien S, Butadej S, Khurana I, Maxwell S, El-Osta A, Chatchomchuan W, Krittiyawong S, Himathongkam T. Prolonged Honeymoon Period in a Thai Patient with Adult-Onset Type 1 Diabetes Mellitus. Case Rep Endocrinol. 2021;2021:3511281. doi: 10.1155/2021/3511281
27. Tan SM, Lindblom RSJ, Ziemann M, Laskowski A, Granata C, Snelson M, Thallas-Bonke V, El-Osta A, Baeza-Garza CD, Caldwell ST, et al. Targeting Methylglyoxal in Diabetic Kidney Disease Using the Mitochondria-Targeted Compound MitoGamide. Nutrients. 2021;13. doi: 10.3390/nu13051457
28. Snelson M, Tan SM, Clarke RE, de Pasquale C, Thallas-Bonke V, Nguyen TV, Penfold SA, Harcourt BE, Sourris KC, Lindblom RS, et al. Processed foods drive intestinal barrier permeability and microvascular diseases. Sci Adv. 2021;7. doi: 10.1126/sciadv.abe4841
29. Sim CB, Phipson B, Ziemann M, Rafehi H, Mills RJ, Watt KI, Abu-Bonsrah KD, Kalathur RKR, Voges HK, Dinh DT, et al. Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor. Circulation. 2021;143:1614-1628. doi: 10.1161/CIRCULATIONAHA.120.051921
30. Shi Z, Tuomilehto J, Kronfeld-Schor N, Alberti GK, Stern N, El-Osta A, Bilu C, Einat H, Zimmet P. The circadian syndrome predicts cardiovascular disease better than metabolic syndrome in Chinese adults. J Intern Med. 2021;289:851-860. doi: 10.1111/joim.13204
31. Riddy DM, Kammoun HL, Murphy AJ, Bosnyak-Gladovic S, De la Fuente Gonzalez R, Merlin J, Ziemann M, Fabb S, Pierce TL, Diepenhorst N, et al. Deletion of GPR21 improves glucose homeostasis and inhibits the CCL2-CCR2 axis by divergent mechanisms. BMJ Open Diabetes Res Care. 2021;9. doi: 10.1136/bmjdrc-2021-002285
32. Renwick N, El-Osta A, Salamon I, Broseghini E, Ferracin M, Poliseno L, Jankauskas SS, Santulli G, Xiao H, Shiu PKT, et al. The Non-Coding RNA Journal Club: Highlights on Recent Papers-9. Noncoding RNA. 2021;7. doi: 10.3390/ncrna7030058
33. Pinzon Cortes JA, El-Osta A. Distinguishable DNA methylation defines disease susceptibility influenced by race and ethnicity. Clin Epigenetics. 2021;13:189. doi: 10.1186/s13148-021-01180-9
34. Lunke S, Maxwell S, Khurana I, K NH, Okabe J, Al-Hasani K, El-Osta A. Epigenetic evidence of an Ac/Dc axis by VPA and SAHA. Clin Epigenetics. 2021;13:58. doi: 10.1186/s13148-021-01050-4
35. Khurana I, Maxwell S, Royce S, Mathiyalagan P, Karagiannis T, Mazarakis N, Vongsvivut J, K NH, Okabe J, Al-Hasani K, et al. SAHA attenuates Takotsubo-like myocardial injury by targeting an epigenetic Ac/Dc axis. Signal Transduct Target Ther. 2021;6:159. doi: 10.1038/s41392-021-00546-y
36. Khurana I, Al-Hasani K, Maxwell S, K NH, Okabe J, Cooper ME, Collombat P, El-Osta A. DNA methylation status correlates with adult beta-cell regeneration capacity. NPJ Regen Med. 2021;6:7. doi: 10.1038/s41536-021-00119-1
37. Felisbino MB, Ziemann M, Khurana I, Okabe J, Al-Hasani K, Maxwell S, Harikrishnan KN, de Oliveira CBM, Mello MLS, El-Osta A. Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways. Sci Rep. 2021;11:2163. doi: 10.1038/s41598-021-81794-4
38. El-Osta A. Editing the cardiac epigenome in broken heart syndrome. Eur Heart J. 2021. doi: 10.1093/eurheartj/ehab632
39. Zimmet P, Shi Z, El-Osta A, Ji L. Chinese Famine and the diabetes mellitus epidemic. Nat Rev Endocrinol. 2020;16:123. doi: 10.1038/s41574-019-0300-9
40. Thewjitcharoen Y, Krittiyawong S, Vongterapak S, Nakasatien S, Aroonparkmongkol S, Khurana I, El-Osta A, Himathongkam T. Clinical Characteristics, Residual Beta-Cell Function and Pancreatic Auto-Antibodies in Thai people with Long-Standing Type 1 Diabetes Mellitus. J ASEAN Fed Endocr Soc. 2020;35:158-162. doi: 10.15605/jafes.035.02.02
41. Tan SM, Ziemann M, Thallas-Bonke V, Snelson M, Kumar V, Laskowski A, Nguyen TV, Huynh K, Clarke MV, Libianto R, et al. Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility. Diabetes. 2020;69:83-98. doi: 10.2337/db19-0043
42. Keating ST, Groh L, van der Heijden C, Rodriguez H, Dos Santos JC, Fanucchi S, Okabe J, Kaipananickal H, van Puffelen JH, Helder L, et al. The Set7 Lysine Methyltransferase Regulates Plasticity in Oxidative Phosphorylation Necessary for Trained Immunity Induced by beta-Glucan. Cell Rep. 2020;31:107548. doi: 10.1016/j.celrep.2020.107548
43. Kaye DM, Shihata WA, Jama HA, Tsyganov K, Ziemann M, Kiriazis H, Horlock D, Vijay A, Giam B, Vinh A, et al. Deficiency of Prebiotic Fiber and Insufficient Signaling Through Gut Metabolite-Sensing Receptors Leads to Cardiovascular Disease. Circulation. 2020;141:1393-1403. doi: 10.1161/CIRCULATIONAHA.119.043081
44. Kaipananickal H, Waheed Khan A, Okabe J, Corcoran SJ, Esler MD, El-Osta A. Targeting Treatment Refractory NET by EZH2 Inhibition in Postural Tachycardia Syndrome. Circ Res. 2020;126:1058-1060. doi: 10.1161/CIRCRESAHA.119.315654
45. Flynn MC, Kraakman MJ, Tikellis C, Lee MKS, Hanssen NMJ, Kammoun HL, Pickering RJ, Dragoljevic D, Al-Sharea A, Barrett TJ, et al. Transient Intermittent Hyperglycemia Accelerates Atherosclerosis by Promoting Myelopoiesis. Circ Res. 2020;127:877-892. doi: 10.1161/CIRCRESAHA.120.316653
46. Bakhet M, Ul-Haq Z, Kamalati T, Lucas A, Majeed A, El-Osta A. Blood tests in general practice: the use of routine data to characterise venous blood testing in North West London, 2016-2018. Br J Gen Pract. 2020;70. doi: 10.3399/bjgp20X711605
47. Bain CR, Ziemann M, Kaspi A, Khan AW, Taylor R, Trahair H, Khurana I, Kaipananickal H, Wallace S, El-Osta A, et al. DNA methylation patterns from peripheral blood separate coronary artery disease patients with and without heart failure. ESC Heart Fail. 2020;7:2468-2478. doi: 10.1002/ehf2.12810
48. Zimmet P, Shi Z, El-Osta A, Ji L. Author Correction: Epidemic T2DM, early development and epigenetics: implications of the Chinese Famine. Nat Rev Endocrinol. 2019;15:312. doi: 10.1038/s41574-019-0199-1
49. Zimmet P, Alberti K, Stern N, Bilu C, El-Osta A, Einat H, Kronfeld-Schor N. The Circadian Syndrome: is the Metabolic Syndrome and much more! J Intern Med. 2019;286:181-191. doi: 10.1111/joim.12924
50. Ziemann M, Kaspi A, El-Osta A. Digital expression explorer 2: a repository of uniformly processed RNA sequencing data. Gigascience. 2019;8. doi: 10.1093/gigascience/giz022
51. Wojtala M, Dabek A, Rybaczek D, Sliwinska A, Swiderska E, Slapek K, El-Osta A, Balcerczyk A. Silencing Lysine-Specific Histone Demethylase 1 (LSD1) Causes Increased HP1-Positive Chromatin, Stimulation of DNA Repair Processes, and Dysregulation of Proliferation by Chk1 Phosphorylation in Human Endothelial Cells. Cells. 2019;8. doi: 10.3390/cells8101212
52. Perez S, Kaspi A, Domovitz T, Davidovich A, Lavi-Itzkovitz A, Meirson T, Alison Holmes J, Dai CY, Huang CF, Chung RT, et al. Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals. PLoS Genet. 2019;15:e1008181. doi: 10.1371/journal.pgen.1008181
53. Perez S, Gevor M, Davidovich A, Kaspi A, Yamin K, Domovich T, Meirson T, Matityahu A, Brody Y, Stemmer SM, et al. Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host-virus interactions. Nucleic Acids Res. 2019;47:2455-2471. doi: 10.1093/nar/gkz052
54. Nguyen MN, Ziemann M, Kiriazis H, Su Y, Thomas Z, Lu Q, Donner DG, Zhao WB, Rafehi H, Sadoshima J, et al. Galectin-3 deficiency ameliorates fibrosis and remodeling in dilated cardiomyopathy mice with enhanced Mst1 signaling. Am J Physiol Heart Circ Physiol. 2019;316:H45-H60. doi: 10.1152/ajpheart.00609.2018
55. Kobow K, Ziemann M, Kaipananickal H, Khurana I, Muhlebner A, Feucht M, Hainfellner JA, Czech T, Aronica E, Pieper T, et al. Genomic DNA methylation distinguishes subtypes of human focal cortical dysplasia. Epilepsia. 2019;60:1091-1103. doi: 10.1111/epi.14934
56. K NH, Okabe J, Mathiyalagan P, Khan AW, Jadaan SA, Sarila G, Ziemann M, Khurana I, Maxwell SS, Du XJ, El-Osta A. Sex-Based Mhrt Methylation Chromatinizes MeCP2 in the Heart. iScience. 2019;17:288-301. doi: 10.1016/j.isci.2019.06.031
57. Hogan MF, Ziemann M, K NH, Rodriguez H, Kaspi A, Esser N, Templin AT, El-Osta A, Kahn SE. RNA-seq-based identification of Star upregulation by islet amyloid formation. Protein Eng Des Sel. 2019;32:67-76. doi: 10.1093/protein/gzz022
58. El-Osta A. Evaluation of genomic methylation indices in juvenile myoclonic epilepsy. Epilepsia. 2019;60:e37-e39. doi: 10.1111/epi.14740
59. Al-Hasani K, Mathiyalagan P, El-Osta A. Epigenetics, cardiovascular disease, and cellular reprogramming. J Mol Cell Cardiol. 2019;128:129-133. doi: 10.1016/j.yjmcc.2019.01.019
60. Zimmet P, Shi Z, El-Osta A, Ji L. Epidemic T2DM, early development and epigenetics: implications of the Chinese Famine. Nat Rev Endocrinol. 2018;14:738-746. doi: 10.1038/s41574-018-0106-1
61. Rodriguez H, El-Osta A. Epigenetic Contribution to the Development and Progression of Vascular Diabetic Complications. Antioxid Redox Signal. 2018;29:1074-1091. doi: 10.1089/ars.2017.7347
62. Marques FZ, Chu PY, Ziemann M, Kaspi A, Kiriazis H, Du XJ, El-Osta A, Kaye DM. Age-Related Differential Structural and Transcriptomic Responses in the Hypertensive Heart. Front Physiol. 2018;9:817. doi: 10.3389/fphys.2018.00817
63. Lipponen A, El-Osta A, Kaspi A, Ziemann M, Khurana I, Kn H, Navarro-Ferrandis V, Puhakka N, Paananen J, Pitkanen A. Transcription factors Tp73, Cebpd, Pax6, and Spi1 rather than DNA methylation regulate chronic transcriptomics changes after experimental traumatic brain injury. Acta Neuropathol Commun. 2018;6:17. doi: 10.1186/s40478-018-0519-z
64. Keating ST, van Diepen JA, Riksen NP, El-Osta A. Epigenetics in diabetic nephropathy, immunity and metabolism. Diabetologia. 2018;61:6-20. doi: 10.1007/s00125-017-4490-1
65. Kaspi A, Khurana I, Ziemann M, Connor T, Spolding B, Zimmet P, Walder K, El-Osta A. Diet during Pregnancy is Implicated in the Regulation of Hypothalamic RNA Methylation and Risk of Obesity in Offspring. Mol Nutr Food Res. 2018;62:e1800134. doi: 10.1002/mnfr.201800134
66. Hagiwara S, Sourris K, Ziemann M, Tieqiao W, Mohan M, McClelland AD, Brennan E, Forbes J, Coughlan M, Harcourt B, et al. RAGE Deletion Confers Renoprotection by Reducing Responsiveness to Transforming Growth Factor-beta and Increasing Resistance to Apoptosis. Diabetes. 2018;67:960-973. doi: 10.2337/db17-0538
67. El-Osta A. Contemporary Trends Emerging in Epigenomics and Metabolism. Antioxid Redox Signal. 2018;29:1019-1022. doi: 10.1089/ars.2017.7473
68. Costantino S, Libby P, Kishore R, Tardif JC, El-Osta A, Paneni F. Epigenetics and precision medicine in cardiovascular patients: from basic concepts to the clinical arena. Eur Heart J. 2018;39:4150-4158. doi: 10.1093/eurheartj/ehx568
69. Cooper ME, El-Osta A, Allen TJ, Watson AMD, Thomas MC, Jandeleit-Dahm KAM. Metabolic Karma-The Atherogenic Legacy of Diabetes: The 2017 Edwin Bierman Award Lecture. Diabetes. 2018;67:785-790. doi: 10.2337/dbi18-0010
70. Brennan EP, Mohan M, McClelland A, Tikellis C, Ziemann M, Kaspi A, Gray SP, Pickering R, Tan SM, Ali-Shah ST, et al. Lipoxins Regulate the Early Growth Response-1 Network and Reverse Diabetic Kidney Disease. J Am Soc Nephrol. 2018;29:1437-1448. doi: 10.1681/ASN.2017101112
71. Rodriguez H, Rafehi H, Bhave M, El-Osta A. Metabolism and chromatin dynamics in health and disease. Mol Aspects Med. 2017;54:1-15. doi: 10.1016/j.mam.2016.09.004
72. Rafehi H, Kaspi A, Ziemann M, Okabe J, Karagiannis TC, El-Osta A. Systems approach to the pharmacological actions of HDAC inhibitors reveals EP300 activities and convergent mechanisms of regulation in diabetes. Epigenetics. 2017;12:991-1003. doi: 10.1080/15592294.2017.1371892
73. Rafehi H, Karagiannis TC, El-Osta A. Pharmacological Histone Deacetylation Distinguishes Transcriptional Regulators. Curr Top Med Chem. 2017;17:1611-1622. doi: 10.2174/1568026617666161104104341
74. Quaife-Ryan GA, Sim CB, Ziemann M, Kaspi A, Rafehi H, Ramialison M, El-Osta A, Hudson JE, Porrello ER. Multicellular Transcriptional Analysis of Mammalian Heart Regeneration. Circulation. 2017;136:1123-1139. doi: 10.1161/CIRCULATIONAHA.117.028252
75. Marques FZ, Nelson E, Chu PY, Horlock D, Fiedler A, Ziemann M, Tan JK, Kuruppu S, Rajapakse NW, El-Osta A, et al. High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice. Circulation. 2017;135:964-977. doi: 10.1161/CIRCULATIONAHA.116.024545
76. Khan AW, Ziemann M, Rafehi H, Maxwell S, Ciccotosto GD, El-Osta A. MeCP2 interacts with chromosomal microRNAs in brain. Epigenetics. 2017;12:1028-1037. doi: 10.1080/15592294.2017.1391429
77. Khan AW, Ziemann M, Corcoran SJ, K NH, Okabe J, Rafehi H, Maxwell SS, Esler MD, El-Osta A. NET silencing by let-7i in postural tachycardia syndrome. JCI Insight. 2017;2:e90183. doi: 10.1172/jci.insight.90183
78. Khan AW, Corcoran SJ, Esler M, El-Osta A. Epigenomic changes associated with impaired norepinephrine transporter function in postural tachycardia syndrome. Neurosci Biobehav Rev. 2017;74:342-355. doi: 10.1016/j.neubiorev.2016.06.015
79. Block T, El-Osta A. Epigenetic programming, early life nutrition and the risk of metabolic disease. Atherosclerosis. 2017;266:31-40. doi: 10.1016/j.atherosclerosis.2017.09.003
80. Ziemann M, Kaspi A, El-Osta A. Evaluation of microRNA alignment techniques. RNA. 2016;22:1120-1138. doi: 10.1261/rna.055509.115
81. Ziemann M, Eren Y, El-Osta A. Gene name errors are widespread in the scientific literature. Genome Biol. 2016;17:177. doi: 10.1186/s13059-016-1044-7
82. Tuano NK, Okabe J, Ziemann M, Cooper ME, El-Osta A. Set7 mediated interactions regulate transcriptional networks in embryonic stem cells. Nucleic Acids Res. 2016;44:9206-9217. doi: 10.1093/nar/gkw621
83. Rafehi H, Khan AW, El-Osta A. Improving understanding of chromatin regulatory proteins and potential implications for drug discovery. Expert Rev Proteomics. 2016;13:435-445. doi: 10.1586/14789450.2016.1159960
84. Rafehi H, El-Osta A. HDAC Inhibition in Vascular Endothelial Cells Regulates the Expression of ncRNAs. Noncoding RNA. 2016;2. doi: 10.3390/ncrna2020004
85. Khurana I, Kaspi A, Ziemann M, Block T, Connor T, Spolding B, Cooper A, Zimmet P, El-Osta A, Walder K. DNA methylation regulates hypothalamic gene expression linking parental diet during pregnancy to the offspring's risk of obesity in Psammomys obesus. Int J Obes (Lond). 2016;40:1079-1088. doi: 10.1038/ijo.2016.64
86. Keating ST, Plutzky J, El-Osta A. Epigenetic Changes in Diabetes and Cardiovascular Risk. Circ Res. 2016;118:1706-1722. doi: 10.1161/CIRCRESAHA.116.306819
87. Karimnia N, Rafehi H, Tuano NK, Ziemann M, K NH, Okabe J, El-Osta A. Current perspectives in Set7 mediated stem cell differentiation. Noncoding RNA. 2016;2. doi: 10.3390/ncrna2040014
88. Gray SP, Di Marco E, Kennedy K, Chew P, Okabe J, El-Osta A, Calkin AC, Biessen EA, Touyz RM, Cooper ME, et al. Reactive Oxygen Species Can Provide Atheroprotection via NOX4-Dependent Inhibition of Inflammation and Vascular Remodeling. Arterioscler Thromb Vasc Biol. 2016;36:295-307. doi: 10.1161/ATVBAHA.115.307012
89. Debski KJ, Pitkanen A, Puhakka N, Bot AM, Khurana I, Harikrishnan KN, Ziemann M, Kaspi A, El-Osta A, Lukasiuk K, Kobow K. Etiology matters - Genomic DNA Methylation Patterns in Three Rat Models of Acquired Epilepsy. Sci Rep. 2016;6:25668. doi: 10.1038/srep25668
90. Balcerczyk A, Rybaczek D, Wojtala M, Pirola L, Okabe J, El-Osta A. Pharmacological inhibition of arginine and lysine methyltransferases induces nuclear abnormalities and suppresses angiogenesis in human endothelial cells. Biochem Pharmacol. 2016;121:18-32. doi: 10.1016/j.bcp.2016.09.013
91. Xu Q, Jennings NL, Sim K, Chang L, Gao XM, Kiriazis H, Lee YY, Nguyen MN, Woodcock EA, Zhang YY, et al. Pathological hypertrophy reverses beta2-adrenergic receptor-induced angiogenesis in mouse heart. Physiol Rep. 2015;3. doi: 10.14814/phy2.12340
92. Sim CB, Ziemann M, Kaspi A, Harikrishnan KN, Ooi J, Khurana I, Chang L, Hudson JE, El-Osta A, Porrello ER. Dynamic changes in the cardiac methylome during postnatal development. FASEB J. 2015;29:1329-1343. doi: 10.1096/fj.14-264093
93. Rodd AL, Ververis K, Sayakkarage D, Khan AW, Rafehi H, Ziemann M, Loveridge SJ, Lazarus R, Kerr C, Lockett T, et al. RNA sequencing supports distinct reactive oxygen species-mediated pathways of apoptosis by high and low size mass fractions of Bay leaf (Lauris nobilis) in HT-29 cells. Food Funct. 2015;6:2507-2524. doi: 10.1039/c5fo00467e
94. Ooi JY, Tuano NK, Rafehi H, Gao XM, Ziemann M, Du XJ, El-Osta A. HDAC inhibition attenuates cardiac hypertrophy by acetylation and deacetylation of target genes. Epigenetics. 2015;10:418-430. doi: 10.1080/15592294.2015.1024406
95. Mathiyalagan P, Keating ST, Al-Hasani K, El-Osta A. Epigenetic-mediated reprogramming of pancreatic endocrine cells. Antioxid Redox Signal. 2015;22:1483-1495. doi: 10.1089/ars.2014.6103
96. Keating ST, El-Osta A. Epigenetics and metabolism. Circ Res. 2015;116:715-736. doi: 10.1161/CIRCRESAHA.116.303936
97. Chen JL, Walton KL, Al-Musawi SL, Kelly EK, Qian H, La M, Lu L, Lovrecz G, Ziemann M, Lazarus R, et al. Development of novel activin-targeted therapeutics. Mol Ther. 2015;23:434-444. doi: 10.1038/mt.2014.221
98. Spolding B, Connor T, Wittmer C, Abreu LL, Kaspi A, Ziemann M, Kaur G, Cooper A, Morrison S, Lee S, et al. Rapid development of non-alcoholic steatohepatitis in Psammomys obesus (Israeli sand rat). PLoS One. 2014;9:e92656. doi: 10.1371/journal.pone.0092656
99. Rafehi H, Balcerczyk A, Lunke S, Kaspi A, Ziemann M, Kn H, Okabe J, Khurana I, Ooi J, Khan AW, et al. Vascular histone deacetylation by pharmacological HDAC inhibition. Genome Res. 2014;24:1271-1284. doi: 10.1101/gr.168781.113
100. Okabe J, Fernandez AZ, Ziemann M, Keating ST, Balcerczyk A, El-Osta A. Endothelial transcriptome in response to pharmacological methyltransferase inhibition. ChemMedChem. 2014;9:1755-1762. doi: 10.1002/cmdc.201402091
101. Mathiyalagan P, Okabe J, Chang L, Su Y, Du XJ, El-Osta A. The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart. Nucleic Acids Res. 2014;42:790-803. doi: 10.1093/nar/gkt896
102. Mathiyalagan P, Keating ST, Du XJ, El-Osta A. Interplay of chromatin modifications and non-coding RNAs in the heart. Epigenetics. 2014;9:101-112. doi: 10.4161/epi.26405
103. Mathiyalagan P, Keating ST, Du XJ, El-Osta A. Chromatin modifications remodel cardiac gene expression. Cardiovasc Res. 2014;103:7-16. doi: 10.1093/cvr/cvu122
104. Latouche C, Heywood SE, Henry SL, Ziemann M, Lazarus R, El-Osta A, Armitage JA, Kingwell BA. Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring. J Nutr. 2014;144:237-244. doi: 10.3945/jn.113.186775
105. Keating ST, Ziemann M, Okabe J, Khan AW, Balcerczyk A, El-Osta A. Deep sequencing reveals novel Set7 networks. Cell Mol Life Sci. 2014;71:4471-4486. doi: 10.1007/s00018-014-1651-y
106. Kaspi A, Ziemann M, Keating ST, Khurana I, Connor T, Spolding B, Cooper A, Lazarus R, Walder K, Zimmet P, El-Osta A. Non-referenced genome assembly from epigenomic short-read data. Epigenetics. 2014;9:1329-1338. doi: 10.4161/15592294.2014.969610
107. Jha JC, Gray SP, Barit D, Okabe J, El-Osta A, Namikoshi T, Thallas-Bonke V, Wingler K, Szyndralewiez C, Heitz F, et al. Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy. J Am Soc Nephrol. 2014;25:1237-1254. doi: 10.1681/ASN.2013070810
108. Demars J, Shmela ME, Khan AW, Lee KS, Azzi S, Dehais P, Netchine I, Rossignol S, Le Bouc Y, El-Osta A, Gicquel C. Genetic variants within the second intron of the KCNQ1 gene affect CTCF binding and confer a risk of Beckwith-Wiedemann syndrome upon maternal transmission. J Med Genet. 2014;51:502-511. doi: 10.1136/jmedgenet-2014-102368
109. Ziemann M, Kaspi A, Lazarus R, El-Osta A. Motif analysis in DNAse hypersensitivity regions uncovers distal cis elements associated with gene expression. Bioinformation. 2013;9:212-215. doi: 10.6026/97320630009212
110. Maxwell SS, Pelka GJ, Tam PP, El-Osta A. Chromatin context and ncRNA highlight targets of MeCP2 in brain. RNA Biol. 2013;10:1741-1757. doi: 10.4161/rna.26921
111. Lunke S, El-Osta A. Applicability of histone deacetylase inhibition for the treatment of spinal muscular atrophy. Neurotherapeutics. 2013;10:677-687. doi: 10.1007/s13311-013-0209-2
112. Licciardi PV, Ververis K, Tang ML, El-Osta A, Karagiannis TC. Immunomodulatory effects of histone deacetylase inhibitors. Curr Mol Med. 2013;13:640-647. doi: 10.2174/1566524011313040013
113. Kobow K, Kaspi A, Harikrishnan KN, Kiese K, Ziemann M, Khurana I, Fritzsche I, Hauke J, Hahnen E, Coras R, et al. Deep sequencing reveals increased DNA methylation in chronic rat epilepsy. Acta Neuropathol. 2013;126:741-756. doi: 10.1007/s00401-013-1168-8
114. Kobow K, El-Osta A, Blumcke I. The methylation hypothesis of pharmacoresistance in epilepsy. Epilepsia. 2013;54 Suppl 2:41-47. doi: 10.1111/epi.12183
115. Kitamura H, Kimura S, Shimamoto Y, Okabe J, Ito M, Miyamoto T, Naoe Y, Kikuguchi C, Meek B, Toda C, et al. Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. FASEB J. 2013;27:4940-4953. doi: 10.1096/fj.13-233528
116. Keating ST, El-Osta A. Epigenetic changes in diabetes. Clin Genet. 2013;84:1-10. doi: 10.1111/cge.12121
117. Keating ST, El-Osta A. Transcriptional regulation by the Set7 lysine methyltransferase. Epigenetics. 2013;8:361-372. doi: 10.4161/epi.24234
118. Keating ST, El-Osta A. Glycemic memories and the epigenetic component of diabetic nephropathy. Curr Diab Rep. 2013;13:574-581. doi: 10.1007/s11892-013-0383-y
119. Gray SP, Di Marco E, Okabe J, Szyndralewiez C, Heitz F, Montezano AC, de Haan JB, Koulis C, El-Osta A, Andrews KL, et al. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation. 2013;127:1888-1902. doi: 10.1161/CIRCULATIONAHA.112.132159
120. Bayles R, Baker EK, Jowett JB, Barton D, Esler M, El-Osta A, Lambert G. Methylation of the SLC6a2 gene promoter in major depression and panic disorder. PLoS One. 2013;8:e83223. doi: 10.1371/journal.pone.0083223
121. Whitham M, Chan MH, Pal M, Matthews VB, Prelovsek O, Lunke S, El-Osta A, Broenneke H, Alber J, Bruning JC, et al. Contraction-induced interleukin-6 gene transcription in skeletal muscle is regulated by c-Jun terminal kinase/activator protein-1. J Biol Chem. 2012;287:10771-10779. doi: 10.1074/jbc.M111.310581
122. Royce SG, Dang W, Yuan G, Tran J, El-Osta A, Karagiannis TC, Tang ML. Effects of the histone deacetylase inhibitor, trichostatin A, in a chronic allergic airways disease model in mice. Arch Immunol Ther Exp (Warsz). 2012;60:295-306. doi: 10.1007/s00005-012-0180-3
123. Rafehi H, Ververis K, Balcerczyk A, Ziemann M, Ooi J, Hu S, Kwa FA, Loveridge SJ, Georgiadis GT, El-Osta A, Karagiannis TC. Investigation of the biological properties of Cinnulin PF in the context of diabetes: mechanistic insights by genome-wide mRNA-Seq analysis. Pathobiol Aging Age Relat Dis. 2012;2. doi: 10.3402/pba.v2i0.11905
124. Rafehi H, Smith AJ, Balcerczyk A, Ziemann M, Ooi J, Loveridge SJ, Baker EK, El-Osta A, Karagiannis TC. Investigation into the biological properties of the olive polyphenol, hydroxytyrosol: mechanistic insights by genome-wide mRNA-Seq analysis. Genes Nutr. 2012;7:343-355. doi: 10.1007/s12263-011-0249-3
125. Rafehi H, El-Osta A, Karagiannis TC. Epigenetic mechanisms in the pathogenesis of diabetic foot ulcers. J Diabetes Complications. 2012;26:554-561. doi: 10.1016/j.jdiacomp.2012.05.015
126. Okabe J, Orlowski C, Balcerczyk A, Tikellis C, Thomas MC, Cooper ME, El-Osta A. Distinguishing hyperglycemic changes by Set7 in vascular endothelial cells. Circ Res. 2012;110:1067-1076. doi: 10.1161/CIRCRESAHA.112.266171
127. Licciardi PV, Kwa FA, Ververis K, Di Costanzo N, Balcerczyk A, Tang ML, El-Osta A, Karagiannis TC. Influence of natural and synthetic histone deacetylase inhibitors on chromatin. Antioxid Redox Signal. 2012;17:340-354. doi: 10.1089/ars.2011.4480
128. Larsson P, Ulfhammer E, Magnusson M, Bergh N, Lunke S, El-Osta A, Medcalf RL, Svensson PA, Karlsson L, Jern S. Role of histone acetylation in the stimulatory effect of valproic acid on vascular endothelial tissue-type plasminogen activator expression. PLoS One. 2012;7:e31573. doi: 10.1371/journal.pone.0031573
129. Keating ST, El-Osta A. Chromatin modifications associated with diabetes. J Cardiovasc Transl Res. 2012;5:399-412. doi: 10.1007/s12265-012-9380-9
130. Kaspi A, Ziemann M, Rafehi H, Lazarus R, El-Osta A. A pipeline for the identification and characterization of chromatin modifications derived from ChIP-Seq datasets. Biochimie. 2012;94:2353-2359. doi: 10.1016/j.biochi.2012.06.002
131. Karagiannis TC, Li X, Tang MM, Orlowski C, El-Osta A, Tang ML, Royce SG. Molecular model of naphthalene-induced DNA damage in the murine lung. Hum Exp Toxicol. 2012;31:42-50. doi: 10.1177/0960327111407228
132. El-Osta A. Glycemic memory. Curr Opin Lipidol. 2012;23:24-29. doi: 10.1097/MOL.0b013e32834f319d
133. El-Osta A. Redox mediating epigenetic changes confer metabolic memories. Circ Res. 2012;111:262-264. doi: 10.1161/CIRCRESAHA.112.274936
134. Diehl P, Fricke A, Sander L, Stamm J, Bassler N, Htun N, Ziemann M, Helbing T, El-Osta A, Jowett JB, Peter K. Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res. 2012;93:633-644. doi: 10.1093/cvr/cvs007
135. Bayles R, Harikrishnan KN, Lambert E, Baker EK, Agrotis A, Guo L, Jowett JB, Esler M, Lambert G, El-Osta A. Epigenetic modification of the norepinephrine transporter gene in postural tachycardia syndrome. Arterioscler Thromb Vasc Biol. 2012;32:1910-1916. doi: 10.1161/ATVBAHA.111.244343
136. Ververis K, Rodd AL, Tang MM, El-Osta A, Karagiannis TC. Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes. Cell Mol Life Sci. 2011;68:4101-4114. doi: 10.1007/s00018-011-0727-1
137. Syreeni A, El-Osta A, Forsblom C, Sandholm N, Parkkonen M, Tarnow L, Parving HH, McKnight AJ, Maxwell AP, Cooper ME, et al. Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes. Diabetes. 2011;60:3073-3080. doi: 10.2337/db11-0073
138. Royce SG, Dang W, Yuan G, Tran J, El Osta A, Karagiannis TC, Tang ML. Resveratrol has protective effects against airway remodeling and airway hyperreactivity in a murine model of allergic airways disease. Pathobiol Aging Age Relat Dis. 2011;1. doi: 10.3402/PBA.v1i0.7134
139. Royce SG, Dang W, Ververis K, De Sampayo N, El-Osta A, Tang ML, Karagiannis TC. Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease. Epigenetics. 2011;6:1463-1470. doi: 10.4161/epi.6.12.18396
140. Rafehi H, Orlowski C, Georgiadis GT, Ververis K, El-Osta A, Karagiannis TC. Clonogenic assay: adherent cells. J Vis Exp. 2011. doi: 10.3791/2573
141. Rafehi H, El-Osta A, Karagiannis TC. Genetic and epigenetic events in diabetic wound healing. Int Wound J. 2011;8:12-21. doi: 10.1111/j.1742-481X.2010.00745.x
142. Pirola L, Balcerczyk A, Tothill RW, Haviv I, Kaspi A, Lunke S, Ziemann M, Karagiannis T, Tonna S, Kowalczyk A, et al. Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells. Genome Res. 2011;21:1601-1615. doi: 10.1101/gr.116095.110
143. Orlowski C, Mah LJ, Vasireddy RS, El-Osta A, Karagiannis TC. Double-strand breaks and the concept of short- and long-term epigenetic memory. Chromosoma. 2011;120:129-149. doi: 10.1007/s00412-010-0305-6
144. Mah LJ, Orlowski C, Ververis K, Vasireddy RS, El-Osta A, Karagiannis TC. Evaluation of the efficacy of radiation-modifying compounds using gammaH2AX as a molecular marker of DNA double-strand breaks. Genome Integr. 2011;2:3. doi: 10.1186/2041-9414-2-3
145. Mah LJ, Orlowski C, Ververis K, El-Osta A, Karagiannis TC. Utility of gammaH2AX as a molecular marker of DNA double-strand breaks in nuclear medicine: applications to radionuclide therapy employing auger electron-emitting isotopes. Curr Radiopharm. 2011;4:59-67. doi: 10.2174/1874471011104010059
146. Kwa FA, Balcerczyk A, Licciardi P, El-Osta A, Karagiannis TC. Chromatin modifying agents - the cutting edge of anticancer therapy. Drug Discov Today. 2011;16:543-547. doi: 10.1016/j.drudis.2011.05.012
147. Frojdo S, Durand C, Molin L, Carey AL, El-Osta A, Kingwell BA, Febbraio MA, Solari F, Vidal H, Pirola L. Phosphoinositide 3-kinase as a novel functional target for the regulation of the insulin signaling pathway by SIRT1. Mol Cell Endocrinol. 2011;335:166-176. doi: 10.1016/j.mce.2011.01.008
148. El-Osta A. Remodeling is at the heart of chromatin: the heartaches of chromatin. Epigenetics. 2011;6:884-887. doi: 10.4161/epi.6.7.16551
149. Demars J, Rossignol S, Netchine I, Lee KS, Shmela M, Faivre L, Weill J, Odent S, Azzi S, Callier P, et al. New insights into the pathogenesis of Beckwith-Wiedemann and Silver-Russell syndromes: contribution of small copy number variations to 11p15 imprinting defects. Hum Mutat. 2011;32:1171-1182. doi: 10.1002/humu.21558
150. Demars J, Le Bouc Y, El-Osta A, Gicquel C. Epigenetic and genetic mechanisms of abnormal 11p15 genomic imprinting in Silver-Russell and Beckwith-Wiedemann syndromes. Curr Med Chem. 2011;18:1740-1750. doi: 10.2174/092986711795496764
151. Chang L, Kiriazis H, Gao XM, Du XJ, El-Osta A. Cardiac genes show contextual SWI/SNF interactions with distinguishable gene activities. Epigenetics. 2011;6:760-768. doi: 10.4161/epi.6.6.16007
152. Vasireddy RS, Tang MM, Mah LJ, Georgiadis GT, El-Osta A, Karagiannis TC. Evaluation of the spatial distribution of gammaH2AX following ionizing radiation. J Vis Exp. 2010. doi: 10.3791/2203
153. Vasireddy RS, Karagiannis TC, El-Osta A. gamma-radiation-induced gammaH2AX formation occurs preferentially in actively transcribing euchromatic loci. Cell Mol Life Sci. 2010;67:291-294. doi: 10.1007/s00018-009-0181-5
154. Tonna S, El-Osta A, Cooper ME, Tikellis C. Metabolic memory and diabetic nephropathy: potential role for epigenetic mechanisms. Nat Rev Nephrol. 2010;6:332-341. doi: 10.1038/nrneph.2010.55
155. Tang MM, Mah LJ, Vasireddy RS, Georgiadis GT, El-Osta A, Royce SG, Karagiannis TC. Quantitation of gammaH2AX foci in tissue samples. J Vis Exp. 2010. doi: 10.3791/2063
156. Siebel AL, Fernandez AZ, El-Osta A. Glycemic memory associated epigenetic changes. Biochem Pharmacol. 2010;80:1853-1859. doi: 10.1016/j.bcp.2010.06.005
157. Pirola L, Balcerczyk A, Okabe J, El-Osta A. Epigenetic phenomena linked to diabetic complications. Nat Rev Endocrinol. 2010;6:665-675. doi: 10.1038/nrendo.2010.188
158. Mathiyalagan P, Chang L, Du XJ, El-Osta A. Cardiac ventricular chambers are epigenetically distinguishable. Cell Cycle. 2010;9:612-617. doi: 10.4161/cc.9.3.10612
159. Mah LJ, Vasireddy RS, Tang MM, Georgiadis GT, El-Osta A, Karagiannis TC. Quantification of gammaH2AX foci in response to ionising radiation. J Vis Exp. 2010. doi: 10.3791/1957
160. Mah LJ, El-Osta A, Karagiannis TC. gammaH2AX: a sensitive molecular marker of DNA damage and repair. Leukemia. 2010;24:679-686. doi: 10.1038/leu.2010.6
161. Mah LJ, El-Osta A, Karagiannis TC. GammaH2AX as a molecular marker of aging and disease. Epigenetics. 2010;5:129-136. doi: 10.4161/epi.5.2.11080
162. Kumar A, El-Osta A, Hussain AA, Marshall J. Increased sequestration of matrix metalloproteinases in ageing human Bruch's membrane: implications for ECM turnover. Invest Ophthalmol Vis Sci. 2010;51:2664-2670. doi: 10.1167/iovs.09-4195
163. Karagiannis TC, Lin AJ, Ververis K, Chang L, Tang MM, Okabe J, El-Osta A. Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes. Aging (Albany NY). 2010;2:659-668. doi: 10.18632/aging.100203
164. Harikrishnan KN, Bayles R, Ciccotosto GD, Maxwell S, Cappai R, Pelka GJ, Tam PP, Christodoulou J, El-Osta A. Alleviating transcriptional inhibition of the norepinephrine slc6a2 transporter gene in depolarized neurons. J Neurosci. 2010;30:1494-1501. doi: 10.1523/JNEUROSCI.4675-09.2010
165. Gibson JH, Slobedman B, K NH, Williamson SL, Minchenko D, El-Osta A, Stern JL, Christodoulou J. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain. BMC Neurosci. 2010;11:53. doi: 10.1186/1471-2202-11-53
166. Fernandez AZ, Siebel AL, El-Osta A. Atherogenic factors and their epigenetic relationships. Int J Vasc Med. 2010;2010:437809. doi: 10.1155/2010/437809
167. Demars J, Shmela ME, Rossignol S, Okabe J, Netchine I, Azzi S, Cabrol S, Le Caignec C, David A, Le Bouc Y, et al. Analysis of the IGF2/H19 imprinting control region uncovers new genetic defects, including mutations of OCT-binding sequences, in patients with 11p15 fetal growth disorders. Hum Mol Genet. 2010;19:803-814. doi: 10.1093/hmg/ddp549
168. Cooper ME, El-Osta A. Epigenetics: mechanisms and implications for diabetic complications. Circ Res. 2010;107:1403-1413. doi: 10.1161/CIRCRESAHA.110.223552
169. Bayles R, Baker E, Eikelis N, El-Osta A, Lambert G. Histone modifications regulate the norepinephrine transporter gene. Cell Cycle. 2010;9:4600-4601. doi: 10.4161/cc.9.22.13888
170. Baker EK, El-Osta A. Epigenetic regulation of multidrug resistance 1 gene expression: profiling CpG methylation status using bisulphite sequencing. Methods Mol Biol. 2010;596:183-198. doi: 10.1007/978-1-60761-416-6_9
171. Southgate RJ, Neill B, Prelovsek O, El-Osta A, Kamei Y, Miura S, Ezaki O, McLoughlin TJ, Zhang W, Unterman TG, Febbraio MA. FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle. J Biol Chem. 2009;284:20440. doi: 10.1074/jbc.a702039200
172. Lunke S, El-Osta A. The emerging role of epigenetic modifications and chromatin remodeling in spinal muscular atrophy. J Neurochem. 2009;109:1557-1569. doi: 10.1111/j.1471-4159.2009.06084.x
173. Hauke J, Riessland M, Lunke S, Eyupoglu IY, Blumcke I, El-Osta A, Wirth B, Hahnen E. Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition. Hum Mol Genet. 2009;18:304-317. doi: 10.1093/hmg/ddn357
174. Brasacchio D, Okabe J, Tikellis C, Balcerczyk A, George P, Baker EK, Calkin AC, Brownlee M, Cooper ME, El-Osta A. Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail. Diabetes. 2009;58:1229-1236. doi: 10.2337/db08-1666
175. Harikrishnan KN, Karagiannis TC, Chow MZ, El-Osta A. Effect of valproic acid on radiation-induced DNA damage in euchromatic and heterochromatic compartments. Cell Cycle. 2008;7:468-476. doi: 10.4161/cc.7.4.5405
176. Gicquel C, El-Osta A, Le Bouc Y. Epigenetic regulation and fetal programming. Best Pract Res Clin Endocrinol Metab. 2008;22:1-16. doi: 10.1016/j.beem.2007.07.009
177. Esler M, Eikelis N, Schlaich M, Lambert G, Alvarenga M, Kaye D, El-Osta A, Guo L, Barton D, Pier C, et al. Human sympathetic nerve biology: parallel influences of stress and epigenetics in essential hypertension and panic disorder. Ann N Y Acad Sci. 2008;1148:338-348. doi: 10.1196/annals.1410.064
178. El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008;205:2409-2417. doi: 10.1084/jem.20081188
179. Southgate RJ, Neill B, Prelovsek O, El-Osta A, Kamei Y, Miura S, Ezaki O, McLoughlin TJ, Zhang W, Unterman TG, Febbraio MA. FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle. J Biol Chem. 2007;282:21176-21186. doi: 10.1074/jbc.M702039200
180. Karagiannis TC, Harikrishnan KN, El-Osta A. Disparity of histone deacetylase inhibition on repair of radiation-induced DNA damage on euchromatin and constitutive heterochromatin compartments. Oncogene. 2007;26:3963-3971. doi: 10.1038/sj.onc.1210174
181. Karagiannis TC, El-Osta A. Will broad-spectrum histone deacetylase inhibitors be superseded by more specific compounds? Leukemia. 2007;21:61-65. doi: 10.1038/sj.leu.2404464
182. Karagiannis TC, El-Osta A. Chromatin modifications and DNA double-strand breaks: the current state of play. Leukemia. 2007;21:195-200. doi: 10.1038/sj.leu.2404478
183. Karagiannis TC, Kn H, El-Osta A. The epigenetic modifier, valproic acid, enhances radiation sensitivity. Epigenetics. 2006;1:131-137. doi: 10.4161/epi.1.3.2896
184. Karagiannis TC, El-Osta A. The paradox of histone deacetylase inhibitor-mediated modulation of cellular responses to radiation. Cell Cycle. 2006;5:288-295. doi: 10.4161/cc.5.3.2421
185. Karagiannis TC, El-Osta A. Modulation of cellular radiation responses by histone deacetylase inhibitors. Oncogene. 2006;25:3885-3893. doi: 10.1038/sj.onc.1209417
186. Karagiannis TC, El-Osta A. Clinical potential of histone deacetylase inhibitors as stand alone therapeutics and in combination with other chemotherapeutics or radiotherapy for cancer. Epigenetics. 2006;1:121-126. doi: 10.4161/epi.1.3.3328
187. Esler M, Alvarenga M, Pier C, Richards J, El-Osta A, Barton D, Haikerwal D, Kaye D, Schlaich M, Guo L, et al. The neuronal noradrenaline transporter, anxiety and cardiovascular disease. J Psychopharmacol. 2006;20:60-66. doi: 10.1177/1359786806066055
188. El-Osta A. Mechanisms of abnormal gene expression in tumor cells. EXS. 2006:351-361. doi: 10.1007/3-7643-7378-4_15
189. Karagiannis TC, Harikrishnan KN, El-Osta A. The histone deacetylase inhibitor, Trichostatin A, enhances radiation sensitivity and accumulation of gammaH2A.X. Cancer Biol Ther. 2005;4:787-793. doi: 10.4161/cbt.4.7.1922
190. Karagiannis TC, El-Osta A. RNA interference and potential therapeutic applications of short interfering RNAs. Cancer Gene Ther. 2005;12:787-795. doi: 10.1038/sj.cgt.7700857
191. Harikrishnan KN, Chow MZ, Baker EK, Pal S, Bassal S, Brasacchio D, Wang L, Craig JM, Jones PL, Sif S, El-Osta A. Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing. Nat Genet. 2005;37:254-264. doi: 10.1038/ng1516
192. Forbes JM, Thorpe SR, Thallas-Bonke V, Pete J, Thomas MC, Deemer ER, Bassal S, El-Osta A, Long DM, Panagiotopoulos S, et al. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. J Am Soc Nephrol. 2005;16:2363-2372. doi: 10.1681/ASN.2005010062
193. Escher G, Hoang A, Georges S, Tchoua U, El-Osta A, Krozowski Z, Sviridov D. Demethylation using the epigenetic modifier, 5-azacytidine, increases the efficiency of transient transfection of macrophages. J Lipid Res. 2005;46:356-365. doi: 10.1194/jlr.D400014-JLR200
194. Bassal S, El-Osta A. DNA damage detection and repair, and the involvement of epigenetic states. Hum Mutat. 2005;25:101-109. doi: 10.1002/humu.20130
195. Baker EK, Johnstone RW, Zalcberg JR, El-Osta A. Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs. Oncogene. 2005;24:8061-8075. doi: 10.1038/sj.onc.1208955
196. Kn H, Bassal S, Tikellis C, El-Osta A. Expression analysis of the epigenetic methyltransferases and methyl-CpG binding protein families in the normal B-cell and B-cell chronic lymphocytic leukemia (CLL). Cancer Biol Ther. 2004;3:989-994. doi: 10.4161/cbt.3.10.1137
197. Karagiannis TC, Smith AJ, El' Osta A. Radio- and chemo-sensitization of human erythroleukemic K562 cells by the histone deacetylase inhibitor Trichostatin A. Hell J Nucl Med. 2004;7:184-191.
198. Karagiannis TC, El-Osta A. Epigenetic changes activate widespread signals in response to double-strand breaks. Cancer Biol Ther. 2004;3:617-623. doi: 10.4161/cbt.3.7.917
199. Karagiannis TC, El-Osta A. Double-strand breaks: signaling pathways and repair mechanisms. Cell Mol Life Sci. 2004;61:2137-2147. doi: 10.1007/s00018-004-4174-0
200. Karagiannis TC, El-Osta A. siRNAs: mechanism of RNA interference, in vivo and potential clinical applications. Cancer Biol Ther. 2004;3:1069-1074. doi: 10.4161/cbt.3.11.1309
201. El-Osta A. The rise and fall of genomic methylation in cancer. Leukemia. 2004;18:233-237. doi: 10.1038/sj.leu.2403218
202. El-Osta A. Understanding the consequences of epigenetic mechanisms and its effects on transcription in health and disease. Cancer Biol Ther. 2004;3:816-818. doi: 10.4161/cbt.3.9.1100
203. El-Osta A. Coordination of epigenetic events. Cell Mol Life Sci. 2004;61:2135-2136. doi: 10.1007/s00018-004-4173-1
204. Berardi P, Russell M, El-Osta A, Riabowol K. Functional links between transcription, DNA repair and apoptosis. Cell Mol Life Sci. 2004;61:2173-2180. doi: 10.1007/s00018-004-4179-8
205. Baker EK, El-Osta A. MDR1, chemotherapy and chromatin remodeling. Cancer Biol Ther. 2004;3:819-824. doi: 10.4161/cbt.3.9.1101
206. El-Osta A. On the use of DNA methylation inhibitors and the reversal of transcriptional silencing. Blood. 2003;101:1656; author reply 1657-1658. doi: 10.1182/blood-2002-10-3003
207. El-Osta A. DNMT cooperativity--the developing links between methylation, chromatin structure and cancer. Bioessays. 2003;25:1071-1084. doi: 10.1002/bies.10345
208. Baker EK, El-Osta A. The rise of DNA methylation and the importance of chromatin on multidrug resistance in cancer. Exp Cell Res. 2003;290:177-194. doi: 10.1016/s0014-4827(03)00342-2
209. El-Osta A, Kantharidis P, Zalcberg JR, Wolffe AP. Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation. Mol Cell Biol. 2002;22:1844-1857. doi: 10.1128/MCB.22.6.1844-1857.2002
210. El-Osta A. FMR1 silencing and the signals to chromatin: a unified model of transcriptional regulation. Biochem Biophys Res Commun. 2002;295:575-581. doi: 10.1016/s0006-291x(02)00682-4
211. El-Osta A, Wolffe AP. Analysis of chromatin-immunopurified MeCP2-associated fragments. Biochem Biophys Res Commun. 2001;289:733-737. doi: 10.1006/bbrc.2001.6023
212. El-Osta A, Baker EK, Wolffe AP. Profiling methyl-CpG specific determinants on transcriptionally silent chromatin. Mol Biol Rep. 2001;28:209-215. doi: 10.1023/a:1015744625049
213. Zalcberg J, Hu XF, Slater A, Parisot J, El-Osta S, Kantharidis P, Chou ST, Parkin JD. MRP1 not MDR1 gene expression is the predominant mechanism of acquired multidrug resistance in two prostate carcinoma cell lines. Prostate Cancer Prostatic Dis. 2000;3:66-75. doi: 10.1038/sj.pcan.4500394
214. Kantharidis P, El-Osta S, Silva M, Lee G, Hu XF, Zalcberg J. Regulation of MDR1 gene expression: emerging concepts. Drug Resist Updat. 2000;3:99-108. doi: 10.1054/drup.2000.0121
215. El-Osta A, Wolffe AP. DNA methylation and histone deacetylation in the control of gene expression: basic biochemistry to human development and disease. Gene Expr. 2000;9:63-75. doi: 10.3727/000000001783992731
216. el-Osta A, Kantharidis P, Zalcberg J. Absolute quantitation of MDR1 transcripts using heterologous DNA standards--validation of the competitive RT-PCR (CRT-PCR) approach. Biotechniques. 1999;26:1114-1116, 1118-1120, 1122 passim. doi: 10.2144/99266st03
217. Wall DM, el-Osta S, Tzelepis D, Bertoncello I, Kantharidis P, Chou ST, Zalcberg JR, Parkin JD. Expression of mdr1 and mrp in the normal B-cell homologue of B-cell chronic lymphocytic leukaemia. Br J Haematol. 1997;96:697-707. doi: 10.1046/j.1365-2141.1997.d01-2090.x
218. Kantharidis P, El-Osta A, deSilva M, Wall DM, Hu XF, Slater A, Nadalin G, Parkin JD, Zalcberg JR. Altered methylation of the human MDR1 promoter is associated with acquired multidrug resistance. Clin Cancer Res. 1997;3:2025-2032.
219. el-Osta S, Kantharidis P, Zalcberg JR. Sequential extraction of DNA and DNA-binding proteins from low cell numbers. Biotechniques. 1997;22:645-648. doi: 10.2144/97224bm15
Research Publications
Scott Maxwell, Jun Okabe, Harikrishnan Kaipananickal, Hanah Rodriguez, Ishant Khurana, Keith Al-Hasani, Bryna S.M. Chow, Eleni Pitsillou, Tom C. Karagiannis, Karin Jandeleit-Dahm, Ronald CW Ma, Yu Huang, Juliana CN Chan, Mark E Cooper and Assam El-Osta. Set7 methyltransferase regulates the phenotypic switch in diabetic glomerular endothelial cells. JASN. 2024. https://journals.lww.com/jasn/abstract/9900/set7_methyltransferase_and_phenotypic_switch_in.275.aspx.
Al-Hasani K, Marikar SN, Kaipananickal H, Maxwell S, Okabe J, Khurana I, Karagiannis T, Liang JJ, Mariana L, Loudovaris T, et al. EZH2 inhibitors promote beta-like cell regeneration in young and adult type 1 diabetes donors. Signal Transduct Target Ther. 2024;9:2. doi: 10.1038/s41392-023-01707-x
Naina Marikar S, Al-Hasani K, Khurana I, Kaipananickal H, Okabe J, Maxwell S, El-Osta A. Pharmacological inhibition of human EZH2 can influence a regenerative beta-like cell capacity with in vitro insulin release in pancreatic ductal cells. Clin Epigenetics. 2023;15:101. doi: 10.1186/s13148-023-01491-z
Khurana I, Kaipananickal H, Maxwell S, Birkelund S, Syreeni A, Forsblom C, Okabe J, Ziemann M, Kaspi A, Rafehi H, et al. Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes. J Clin Invest. 2023;133. doi: 10.1172/JCI160959
Khurana I, Howard NJ, Maxwell S, Du Preez A, Kaipananickal H, Breen J, Buckberry S, Okabe J, Al-Hasani K, Nakasatien S, et al. Circulating epigenomic biomarkers correspond with kidney disease susceptibility in high-risk populations with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2023;204:110918. doi: 10.1016/j.diabres.2023.110918
Al-Hasani K, Khurana I, Mariana L, Loudovaris T, Maxwell S, Harikrishnan KN, Okabe J, Cooper ME, El-Osta A. Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor. Signal Transduct Target Ther. 2022;7:248. doi: 10.1038/s41392-022-01034-7
Khurana I, Maxwell S, Royce S, Mathiyalagan P, Karagiannis T, Mazarakis N, Vongsvivut J, K NH, Okabe J, Al-Hasani K, et al. SAHA attenuates Takotsubo-like myocardial injury by targeting an epigenetic Ac/Dc axis. Signal Transduct Target Ther. 2021;6:159. doi: 10.1038/s41392-021-00546-y
Khurana I, Al-Hasani K, Maxwell S, K NH, Okabe J, Cooper ME, Collombat P, El-Osta A. DNA methylation status correlates with adult beta-cell regeneration capacity. NPJ Regen Med. 2021;6:7. doi: 10.1038/s41536-021-00119-1