Dimitrios Cakouros

Research Interests

Epigenetics Ageing, Frailty and Mobility

Dr Dimitrios Cakouros

Lecturer

School of Pharmacy and Biomedical Science

College of Health

Eligible to supervise Masters and PhD - email supervisor to discuss availability.

The greatest risk factor for all chronic diseases today is aging with stem cell ageing being paramount to tissue degeneration affecting our overall health and life-span . Our epigenome, is defined by enzyme induced chemical modifications of our DNA and histones that alters the function of our genome. All aging organisms studied to date exhibit ‘Epigenetic Drift’, with increasing evidence that diet and lifestyle causes epigenetic changes, which impacts the structure and function of our genome therefore influencing our lifespan. Research within my group has been heavily focused on bone aging and related diseases such as osteoporosis. We use bone marrow derived mesenchymal stem cells (MSC) to understand how Epigenetic changes occur to drive aging and how diet and life style communicates with our genome via our epigenome. This includes examining all aspects of adult stem cell aging ie senescence, differentiation, metabolomics, gene expression and oxidative stress with the ultimate aim of reversing stem cell aging. In addition we explore other human conditions related with MSC deregulation including craniosynostosis in young children.Over the years we have discovered epigenetic enzymes that are key regulators of stem cell function and lifespan and our current projects involve both human and mouse work including generating conditional knockout strains, in vivo analysis including Skeletal analysis throughout development, bone fracture, ectopic bone formation, osteoporotic models, isolating and purifying different stem cell populations for in vitro characterisation. This includes RNA-seq, ChIP-seq, Me-DIP/5hMe-DIP to discover epigenetic signatures, novel epigenetic enzymes and chemical inhibitors to modify the behaviour of stem cells with the aim of rejuvinating MSC's and enhance their ability for self renewal. Currently, we are also endeavouring in unraveling the epigenetic changes that drive aging of other stem cells with the hope of discovering common deregulated epigenetic enzymes which are central to stem cell aging. These projects also include the supervision of junior staff, Honours and postgraduate students.

Molecular regulation of Stem Cell Aging Group.

The greatest risk factor for all chronic diseases today is aging with stem cell ageing being paramount to tissue degeneration affecting our overall health and life-span . Our epigenome, is defined by enzyme induced chemical modifications of our DNA and histones that alters the function of our genome. All aging organisms studied to date exhibit ‘Epigenetic Drift’, with increasing evidence that diet and lifestyle causes epigenetic changes, which impacts the structure and function of our genome therefore influencing our lifespan. Research within my group has been heavily focused on bone aging and related diseases such as osteoporosis. We use bone marrow derived  mesenchymal stem cells (MSC) to understand how Epigenetic changes occur to drive aging and how diet and life style communicates with our genome via our epigenome. This includes examining all aspects of adult stem cell aging ie senescence, differentiation, metabolomics, gene expression and oxidative stress with the ultimate aim of reversing stem cell aging. In addition we explore other human conditions related with MSC deregulation including craniosynostosis in young children.

Over the years we have discovered epigenetic enzymes that are key regulators of stem cell function and lifespan and our current projects involve both human and mouse work including generating conditional knockout strains, in vivo analysis including Skeletal analysis throughout development, bone fracture, ectopic bone formation, osteoporotic models, isolating and purifying different stem cell populations for in vitro characterisation.  This includes RNA-seq, ChIP-seq, Me-DIP/5hMe-DIP to discover epigenetic signatures, novel epigenetic enzymes and chemical inhibitors to modify the behaviour of stem cells with the aim of rejuvinating MSC's and enhance their ability for self renewal. Currently, we are also endeavouring in unraveling the epigenetic changes that drive aging of other stem cells, including cardiac progenitor cells, neural stem cells and pancreatic stem cells with the hope of discovering common deregulated epigenetic enzymes which are central to stem cell aging. These projects also include the supervision of junior staff, Honours and postgraduate students.

Current Projects available:

1. Deciphering the mechanism of a novel histone demethylase in driving Mesenchymal Stem cell lineage determination, aging and Osteoporosis.

2. Identifying Novel gene targets driving hypergylcaemia induced bone loss and Mesenchymal Stem Cell aging.

3. Rejuvinating adult mesenchymal stem cells by metabolite supplementation

3. Identifying epigenetic regulators of cardiac progenitor cell aging and their role in heart failure.

Date Position Institution name
2022 - ongoing Lecturer University of Adelaide
2022 - ongoing Post Doctoral Researcher University of Adelaide

Date Institution name Country Title
1997 - 2002 Australian National University Australia PhD
1992 - 1995 University of Adelaide Australia BSC

Year Citation
2025 Plakhova, N., Panagopoulos, V., Cantley, M. D., Trainor, L. J., Hewett, D. R., Clark, K. C., . . . Vandyke, K. (2025). Age-related mesenchymal stromal cell senescence is associated with progression from MGUS to multiple myeloma.. Leukemia, 39(6), 1464-1475.
DOI Scopus1 WoS3 Europe PMC1
2025 Smith, N., Cakouros, D., Ryan, F. J., Lynn, D. J., Paton, S., Arthur, A., & Gronthos, S. (2025). DNA hydroxymethylases Tet1 and Tet2 regulate bone aging and BMSC metabolism through the IGF-1/ mTOR signalling axis. Stem Cells, 43(8), sxaf026-1-sxaf026-17.
DOI
2023 Smith, N., Shirazi, S., Cakouros, D., & Gronthos, S. (2023). Impact of Environmental and Epigenetic Changes on Mesenchymal Stem Cells during Aging. International Journal of Molecular Sciences, 24(7), 6499.
DOI Scopus14 WoS10 Europe PMC10
2023 Pribadi, C., Cakouros, D., Camp, E., Anderson, P. J., & Gronthos, S. (2023). KDM6A Mediated Regulation of Cranial Frontal Bone Suture Fusion in Mice is Sex-Dependent. Stem Cells and Development, 32(13-14), 398-409.
DOI Scopus4 WoS4 Europe PMC2
2022 Kutyna, M. M., Kok, C. H., Lim, Y., Tran, E. N. H., Campbell, D., Paton, S., . . . Hiwase, D. K. (2022). A senescence stress secretome is a hallmark of therapy-related myeloid neoplasm stromal tissue occurring soon after cytotoxic exposure. Leukemia, 36(11), 2678-2689.
DOI Scopus17 WoS17 Europe PMC17
2020 Kutyna, M. M., Wee, L. Y. A., Paton, S., Cakouros, D., Arthur, A., Chhetri, R., . . . Hiwase, D. K. (2020). Therapy-Related Myeloid Neoplasm Has a Distinct Pro-Inflammatory Bone Marrow Microenvironment and Delayed DNA Damage Repair. Blood, 136(Supplement 1), 37-38.
DOI
2020 Cakouros, D., & Gronthos, S. (2020). The changing epigenetic landscape of Mesenchymal Stem/Stromal Cells during aging.. Bone, 137, 1-13.
DOI Scopus28 WoS26 Europe PMC23
2020 Cakouros, D., & Gronthos, S. (2020). Epigenetic regulators of mesenchymal stem/stromal cell lineage determination. Current Osteoporosis Reports, 18(5), 597-605.
DOI Scopus34 WoS31 Europe PMC26
2020 Pribadi, C., Camp, E., Cakouros, D., Anderson, P., Glackin, C., & Gronthos, S. (2020). Pharmacological targeting of KDM6A and KDM6B, as a novel therapeutic strategy for treating craniosynostosis in Saethre-Chotzen syndrome. Stem Cell Research and Therapy, 11(1), 529-1-529-14.
DOI Scopus16 WoS16 Europe PMC14
2019 Cakouros, D., Hemming, S., Gronthos, K., Liu, R., Zannettino, A., Shi, S., & Gronthos, S. (2019). Specific functions of TET1 and TET2 in regulating mesenchymal cell lineage determination. Epigenetics and Chromatin, 12(1), 20.
DOI Scopus65 WoS61 Europe PMC58
2019 Cakouros, D., & Gronthos, S. (2019). Epigenetic Regulation of Bone Marrow Stem Cell Aging: Revealing Epigenetic Signatures associated with Hematopoietic and Mesenchymal Stem Cell Aging. AGING AND DISEASE, 10(1), 174-189.
DOI Scopus63 WoS53 Europe PMC57
2017 Hemming, S., Cakouros, D., Codrington, J., Vandyke, K., Arthur, A., Zannettino, A., & Gronthos, S. (2017). EZH2 deletion in early mesenchyme compromises postnatal bone microarchitecture & structural integrity and accelerates remodeling. FASEB Journal, 31(3), 1011-1027.
DOI Scopus54 WoS56 Europe PMC52
2016 Arthur, A., Cakouros, D., Cooper, L., Nguyen, T., Isenmann, S., Zannettino, A., . . . Gronthos, S. (2016). Twist-1 enhances bone marrow mesenchymal stromal cell support of hematopoiesis by modulating CXCL12 expression. Stem Cells, 34(2), 504-509.
DOI Scopus21 WoS21 Europe PMC20
2016 Hemming, S., Cakouros, D., Vandyke, K., Davis, M. J., Zannettino, A. C. W., & Gronthos, S. (2016). Identification of novel EZH2 targets regulating osteogenic differentiation in mesenchymal stem cells. Stem Cells and Development, 25(12), 909-921.
DOI Scopus69 WoS67 Europe PMC58
2015 Cakouros, D., Isenmann, S., Hemming, S., Menicanin, D., Camp, E., Zannetinno, A., & Gronthos, S. (2015). Novel basic helix-loop-helix transcription factor hes4 antagonizes the function of twist-1 to regulate lineage commitment of bone marrow stromal/stem cells. Stem Cells and Development, 24(11), 1297-1308.
DOI Scopus27 WoS28 Europe PMC27
2014 Hemming, S., Cakouros, D., & Gronthos, S. (2014). Detachment of mesenchymal stem cells with trypsin/EDTA has no effect on apoptosis detection. Stem Cells, 32(7), 1991-1992.
DOI Scopus1
2014 Hemming, S., Cakouros, D., Isenmann, S., Cooper, L., Menicanin, D., Zannettino, A., & Gronthos, S. (2014). EZH2 and KDM6A act as an epigenetic switch to regulate mesenchymal stem cell lineage specification. Stem cells, 32(3), 802-815.
DOI Scopus232 WoS218 Europe PMC197
2013 Denton, D., Aung Htut, M., Lorensuhewa, N., Nicholson, S., Zhu, W., Mills, K., . . . Kumar, S. (2013). UTX coordinates steroid hormone-mediated autophagy and cell death. Nature Communications, 4(1), 1-11.
DOI Scopus53 WoS48 Europe PMC37
2012 Cakouros, D., Isenmann, S., Cooper, L., Zannettino, A., Anderson, P., Glackin, C., & Gronthos, S. (2012). Twist-1 Induces Ezh2 Recruitment Regulating Histone Methylation along the Ink4A/Arf Locus in Mesenchymal Stem Cells. Molecular and Cellular Biology, 32(8), 1433-1441.
DOI Scopus111 WoS106 Europe PMC91
2010 Cakouros, D., Raices, R., Gronthos, S., & Glackin, C. (2010). Twist-ing cell fate: mechanistic insights into the role of twist in lineage specification/differentiation and tumorigenesis. Journal of Cellular Biochemistry, 110(6), 1288-1298.
DOI Scopus36 WoS34 Europe PMC31
2009 Ho, L., Taylor, R., Dorstyn, L., Cakouros, D., Bouillet, P., & Kumar, S. (2009). A tumor suppressor function for caspase-2. Proceedings of the National Academy of Sciences of the United States of America, 106(13), 5336-5341.
DOI Scopus152 WoS142 Europe PMC136
2008 Cakouros, D., Mills, K., Denton, D., Paterson, A., Daish, T., & Kumar, S. (2008). dLKR/SDH regulates hormone-mediated histone arginine methylation and transcription of cell death genes. Journal of Cell Biology, 182(3), 481-495.
DOI Scopus26 WoS25 Europe PMC21
2007 Isenmann, S., Cakouros, D., Zannettino, A., Shi, S., & Gronthos, S. (2007). hTERT Transcription is repressed by Cbfa1 in human mesenchymal stem cell populations. Journal of Bone and Mineral Research, 22(6), 897-906.
DOI Scopus25 WoS23 Europe PMC19
2005 Korten, Z., Cakouros, D., & Kumar, S. (2005). Ecdysone-mediated up-regulation of the effector caspase DRICE is required for hormone-dependent apoptosis in Drosophila cells. Journal of Biological Chemistry, 280(12), 11981-11986.
DOI Scopus59 WoS52 Europe PMC48
2004 Kumar, S., & Cakouros, D. (2004). Transcriptional control of the core cell-death machinery. Trends in Biochemical Sciences, 29(4), 193-196.
DOI Scopus60 WoS60 Europe PMC52
2004 Cakouros, D., Daish, T., & Kumar, S. (2004). Ecdysone receptor directly binds the promoter of the Drosophila caspase dronc, regulating its expression in specific tissues. Journal of Cell Biology, 165(5), 631-640.
DOI Scopus89 WoS88 Europe PMC74
2004 Cakouros, D., Daish, T., Mills, K., & Kumar, S. (2004). An arginine-histone methyltransferase, CARMER, coordinates ecdysone-mediated apoptosis in drosophila cells. Journal of Biological Chemistry, 279(18), 18467-18471.
DOI Scopus31 WoS31 Europe PMC30
2003 Daish, T., Cakouros, D., & Kumar, S. (2003). Distinct promoter regions regulate spatial and temporal expression of the Drosophila caspase dronc. Cell Death and Differentiation, 10(12), 1348-1356.
DOI Scopus32 WoS31 Europe PMC27
2002 Dorstyn, L., Read, S., Cakouros, D., Huh, J., Hay, B., & Kumar, S. (2002). The role of cytochrome c in caspase activation in Drosophila melanogaster cells. Journal of Cell Biology, 156(6), 1089-1098.
DOI Scopus172 WoS166 Europe PMC148
2002 Cakouros, D., Daish, T., Martin, D., Baehrecke, E., & Kumar, S. (2002). Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex. Journal of Cell Biology, 157(6), 985-995.
DOI Scopus90 WoS87 Europe PMC76
2001 Cakouros, D., Cockerill, P. N., Bert, A. G., Mital, R., Roberts, D. C., & Shannon, M. F. (2001). A NF-kappa B/Sp1 region is essential for chromatin remodeling and correct transcription of a human granulocyte-macrophage colony-stimulating factor transgene. Journal of Immunology, 167(1), 302-310.
DOI WoS33 Europe PMC28
2001 Cakouros, D., Cockerill, P. N., Bert, A. G., Mital, R., Roberts, D. C., & Shannon, M. F. (2001). A NF-κB/Sp1 region is essential for chromatin remodeling and correct transcription of a human granulocyte-macrophage colony-stimulating factor transgene. Journal of Immunology, 167(1), 302-310.
DOI Scopus35
1999 Shang, C., Attema, J., Cakouros, D., Cockerill, P. N., & Shannon, M. F. (1999). Nuclear factor of activated T cells contributes to the function of the CD28 response region of the granulocyte macrophage-colony stimulating factor promoter. International Immunology, 11(12), 1945-1956.
DOI Scopus27 WoS27 Europe PMC23

Year Citation
2017 Hemming, S., & Cakouros, D. (2017). Epigenetic regulation of mesenchymal stem/stromal cell growth and multipotentiality. In K. Atkinson (Ed.), The Biology and Therapeutic Application of Mesenchymal Cells (Vol. 1-2, pp. 41-57). Hoboken, New Jersey: John Wiley and Sons.
DOI
2003 Kumar, S., & Cakouros, D. (2003). The role of caspases in apoptosis. In S. Grimm (Ed.), Genetics of apoptosis (pp. 31-45). 9 Newtec Place, Magdalen Road, Oxford OX4 1RE, UK: Bios Scientific Publishers Ltd.

Year Citation
2021 Kutyna, M. M., Kok, C. H., Paton, S., Cakouros, D., Arthur, A., Hughes, T. P., . . . Hiwase, D. (2021). Distinct Senescent Bone Marrow Microenvironment in Therapy-Related Myeloid Neoplasms. In BLOOD Vol. 138 (pp. 4 pages). GA, Atlanta: AMER SOC HEMATOLOGY.
DOI WoS1

Year Citation
2019 Kutyna, M. M., Wee, A., Paton, S., Cakouros, D., Arthur, A., Chhetri, R., . . . Hiwase, D. K. (2019). Aberrant Bone Marrow Microenvironment in Therapy Related Myeloid Neoplasm (t-MN). Poster session presented at the meeting of BLOOD. FL, Orlando: ELSEVIER.
DOI WoS2
2018 Cakouros, D., Hemming, S., Pribadi, C., Zannettino, A., & Gronthos, S. (2018). EPIGENETIC ENZYMES AND THEIR EMERGING ROLE IN MESENCHYMAL STEM CELL LINEAGE DETERMINATION. Poster session presented at the meeting of JOURNAL OF GENE MEDICINE. Univ Technol Sydney, Sydney, AUSTRALIA: WILEY.

1. Transcriptional Control of Programmed Cell Death. (NHMRC)   2006-2008

2. Identifying an Epigenetic enzyme regulating programmed cell death. (Cancer Council Australia) 2009

3. Twist-1 Mediated Regulation of Multipotential Mesenchymal Stem Cell Self-Renewal and Cell Fate Determination. (NHMRC) 2013-2015

4. Histone Demethylase KDM6A is a novel target for treating craniosynostosis in children with Saethre Chotzen Syndrome. (NHMRC) 2018-2020.

5. Deregulation of DNA hydroxymethylases Tet1/Tet2 compromises skeletal Integrity during ageing and bone disease. (NHMRC) 2018-2021.

6. Epigenetic Regulation of Bone Regeneration. Osteology Foundation (Switzerland) Advanced  Research Grant. 2021-2022

7.  Epigenetic Regulation of Bone Regeneration. 2022-2023. Craniofacial Australia Foundation.

8. Investigating high fat/glucose diet on Mesenchymal Stem Cells. FHMS research Grant. 2024. Principal Investigator

1. Human Biology 1B

2. Human Anatomy and Physiology IA

3. Human Anatomy and Physiology IB

4. Dental Science and Practise

5. Foundations of Medicine

6. Integrated and Applied Systems Physiology

7. Medical Studies 1

8. Physiology IIA

9. Medical Studies 2B

Date Role Research Topic Program Degree Type Student Load Student Name
2022 Co-Supervisor Identification of epigenetic factors deregulated in skeletal stem cells during high glucose medicated inhibition of bone formation Doctor of Philosophy Doctorate Part Time Mrs Suzanna Shirazi

Date Role Research Topic Program Degree Type Student Load Student Name
2020 - 2024 Co-Supervisor Deregulation of DNA Hydroxymethylases TET1 and TET2 Compromises Skeletal Integrity During Ageing Doctor of Philosophy Doctorate Full Time Mr Nicholas John Smith
2018 - 2022 Co-Supervisor The Role of Epigenetic Modifiers, Kdm6a and Kdm6b, in Calvarial Suture Development and Craniosynostosis Doctor of Philosophy Doctorate Full Time Miss Clara Pribadi
2012 - 2016 External Supervisor Epignetic Regulation of Histone Three Lysine Twenty Seven Tri Methylation Dictates Mesenchymal Stem Cell Lineage Commitment, Lifespan and Murine Skeletal Development Doctor of Philosophy Doctorate Full Time Miss Sarah Elizabeth Hemming
2006 - 2009 Co-Supervisor Analysis of the Function and Regulation of the Centrosomal Protein NEDD1 During Cell Division and Development Doctor of Philosophy Doctorate Full Time Jantina Anna Manning

Date Role Committee Institution Country
2021 - ongoing Member Australian Epigenetics Alliance University of Adelaide Australia
2015 - ongoing Co-Founder Epigenetics Consortium of South Australia University of Adelaide Australia
2013 - 2015 Member ASMR University of Adelaide Australia

Date Role Membership Country
2013 - ongoing Member Australian Asian Stem Cell Society Australia

Date Role Editorial Board Name Institution Country
2014 - ongoing Editor Journal of Stem Cells Research, Reviews and Reports University of Adelaide Australia

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