I am working as part of an academic team on a project aimed at completing a Phase 1 Clinical Trial using pluripotent stem cell derived cardiomyocytes for the treatment of “no-option” end stage heart failure. My primary role in the team is the development of a scalable bioreactor based process for the produciton of pluripotent stem cell derived cardiomyocytes. This process has been developed to meet GMP and local regulatory requirements. Ancilliary to this, I have been wokring on the development and validation of safety assays in line with ICH guidelines for the clinical trial.
Coronary heart disease is the leading cause of death in Australia, representing one in five deaths and accounting for approximately 443 hospitalizations per day. Heart failure costs Australia approximately $1 billion per annum. Following myocardial infarction (a heart attack) it is estimated that approximately 1 billion heart cells are lost. The loss of this heart muscle results in a decreased capacity for the heart to effectively pump blood through the body. Several clinical trials internationally have attempted to restore heart function using non cardiac cell types including skeletal myoblasts, bone marrow derived cells and mesenchymal stem cells. However, these clinical trials have yielded minimal improvements. Our team aims to be the first in Australia to try to replace this lost tissue with the very cell type that is lost following a heart attack (cardiomyocytes). These cardiomyocytes are produced from induced pluripotent stem cells, through a process with the potential to yield the high number of cells required to replace the lost tissue. Preclinical data from our team and others internationally indicates a strong potential for this therapy.
Journal Article: Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias
Selvakumar, Dinesh, Clayton, Zoe E., Prowse, Andrew, Dingwall, Steve, Kim, Sul Ki, Reyes, Leila, George, Jacob, Shah, Haisam, Chen, Siqi, Leung, Halina H. L., Hume, Robert D., Tjahjadi, Laurentius, Igoor, Sindhu, Skelton, Rhys J. P., Hing, Alfred, Paterson, Hugh, Foster, Sheryl L., Pearson, Lachlan, Wilkie, Emma, Marcus, Alan D., Jeyaprakash, Prajith, Wu, Zhixuan, Chiu, Han Shen, Ongtengco, Cherica Felize J., Mulay, Onkar, McArthur, Jeffrey R., Barry, Tony, Lu, Juntang, Tran, Vu ... Chong, James J. H. (2024). Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias. Nature Cardiovascular Research, 1-21. doi: 10.1038/s44161-023-00419-3
Conference Publication: Cellular heterogeneity of pluripotent stem cell derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias
Selvakumar, D., Clayton, Z., Prowse, A., Dingwall, S., George, J., Shah, H., Paterson, H., Jeyaprakesh, P., Wu, Z., Campbell, T., Kotake, Y., Turnbull, S., Nguyen, Q., Grieve, S., Palpant, N., Pathan, F., Kizana, E., Kumar, S., Gray, P. and Chong, J. (2022). Cellular heterogeneity of pluripotent stem cell derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias. 70th Annual Scientific Meeting of the Cardiac Society of Australia and New Zealand, Gold Coast, QLD Australia, 11-14 August 2022. Chatswood, NSW Australia: Elsevier. doi: 10.1016/j.hlc.2022.06.004
Quek, Hazel, Luff, John, Cheung, KaGeen, Kozlov, Sergei, Gatei, Magtouf, Lee, C. Soon, Bellingham, Mark C., Noakes, Peter G., Lim, Yi Chieh, Barnett, Nigel L., Dingwall, Steven, Wolvetang, Ernst, Mashimo, Tomoji, Roberts, Tara L. and Lavin, Martin F. (2016). Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage. Journal of Leukocyte Biology, 101 (4), 927-947. doi: 10.1189/jlb.4VMA0716-316R
Studying the basis of and developing new therapies to treat heart disease
(2023–2024) IPF Healthy - Medical Research
Selvakumar, Dinesh, Clayton, Zoe E., Prowse, Andrew, Dingwall, Steve, Kim, Sul Ki, Reyes, Leila, George, Jacob, Shah, Haisam, Chen, Siqi, Leung, Halina H. L., Hume, Robert D., Tjahjadi, Laurentius, Igoor, Sindhu, Skelton, Rhys J. P., Hing, Alfred, Paterson, Hugh, Foster, Sheryl L., Pearson, Lachlan, Wilkie, Emma, Marcus, Alan D., Jeyaprakash, Prajith, Wu, Zhixuan, Chiu, Han Shen, Ongtengco, Cherica Felize J., Mulay, Onkar, McArthur, Jeffrey R., Barry, Tony, Lu, Juntang, Tran, Vu ... Chong, James J. H. (2024). Cellular heterogeneity of pluripotent stem cell-derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias. Nature Cardiovascular Research, 1-21. doi: 10.1038/s44161-023-00419-3
Quek, Hazel, Luff, John, Cheung, KaGeen, Kozlov, Sergei, Gatei, Magtouf, Lee, C. Soon, Bellingham, Mark C., Noakes, Peter G., Lim, Yi Chieh, Barnett, Nigel L., Dingwall, Steven, Wolvetang, Ernst, Mashimo, Tomoji, Roberts, Tara L. and Lavin, Martin F. (2016). Rats with a missense mutation in Atm display neuroinflammation and neurodegeneration subsequent to accumulation of cytosolic DNA following unrepaired DNA damage. Journal of Leukocyte Biology, 101 (4), 927-947. doi: 10.1189/jlb.4VMA0716-316R
A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype
Quek, Hazel, Luff, John, Cheung, KaGeen, Kozlov, Sergei, Gatei, Magtouf, Lee, C Soon, Bellingham, Mark C., Noakes, Peter G., Lim, Yi Chieh, Barnett, Nigel L., Dingwall, Steven, Wolvetang, Ernst, Mashimo, Tomoji, Roberts, Tara L. and Lavin, Martin F. (2016). A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype. Human Molecular Genetics, 26 (1), 109-123. doi: 10.1093/hmg/ddw371
Neoplastic human embryonic stem cells as a model of radiation resistance of human cancer stem cells
Dingwall, Steve, Lee, Jung Bok, Guezguez, Borhane, Fiebig, Aline, McNicol, Jamie, Boreham, Douglas, Collins, Tony J. and Bhatia, Mick (2015). Neoplastic human embryonic stem cells as a model of radiation resistance of human cancer stem cells. Oncotarget, 6 (26), 22258-22269. doi: 10.18632/oncotarget.4165
Salci, Kyle R., Lee, Jong-Hee, Laronde, Sarah, Dingwall, Steve, Kushwah, Rahul, Fiebig-Comyn, Aline, Leber, Brian, Foley, Ronan, Dal Cin, Arianna and Bhatia, Mickie (2015). Cellular reprogramming allows generation of autologous hematopoietic progenitors from AML patients that are devoid of patient-specific genomic aberrations. Stem Cells, 33 (6), 1839-49. doi: 10.1002/stem.1994
Dingwall, Steven, Brooks, Andrew, Apte, Simon H., Waters, Mike, Lavin, Martin F. and Wolvetang, Ernst J. (2015). Expression of Histocompatibility 2 Blastocyst (H2-Bl) in embryonic stem cells inhibits CD8+ T-cell activation but is not sufficient to facilitate graft tolerance. Journal of Stem Cell Research and Therapy, 5 (12) 1000320, 1-8. doi: 10.4172/2157-7633.1000320
Risueño, Ruth M, Campbell, Clinton J V, Dingwall, Steve, Levadoux-Martin, Marilyne, Leber, Brian, Xenocostas, Anargyros and Bhatia, Mickie (2011). Identification of T-lymphocytic leukemia-initiating stem cells residing in a small subset of patients with acute myeloid leukemic disease. Blood, 117 (26), 7112-7120. doi: 10.1182/blood-2011-01-329078
Dingwall, S., Mills, C. E., Phan, N., Taylor, K. and Boreham, D. R. (2011). Human health and the biological effects of tritium in drinking water: Prudent policy through science - Addressing the ODWAC new recommendation. Dose-Response, 9 (1), 6-31. doi: 10.2203/dose-response.10-048.Boreham
Characterization of human embryonic stem cells with features of neoplastic progression
Werbowetski-Ogilvie, Tamra E, Bossé, Marc, Stewart, Morag, Schnerch, Angelique, Ramos-Mejia, Veronica, Rouleau, Anne, Wynder, Tracy, Smith, Mary-Jo, Dingwall, Steve, Carter, Tim, Williams, Christopher, Harris, Charles, Dolling, Joanna, Wynder, Christopher, Boreham, Doug and Bhatia, Mickie (2009). Characterization of human embryonic stem cells with features of neoplastic progression. Nature Biotechnology, 27 (1), 91-7. doi: 10.1038/nbt.1516
Selvakumar, D., Clayton, Z., Prowse, A., Dingwall, S., George, J., Shah, H., Paterson, H., Jeyaprakesh, P., Wu, Z., Campbell, T., Kotake, Y., Turnbull, S., Nguyen, Q., Grieve, S., Palpant, N., Pathan, F., Kizana, E., Kumar, S., Gray, P. and Chong, J. (2022). Cellular heterogeneity of pluripotent stem cell derived cardiomyocyte grafts is mechanistically linked to treatable arrhythmias. 70th Annual Scientific Meeting of the Cardiac Society of Australia and New Zealand, Gold Coast, QLD Australia, 11-14 August 2022. Chatswood, NSW Australia: Elsevier. doi: 10.1016/j.hlc.2022.06.004
Neuroinflammation drives the neuronal degenerative phenotype in a rat model of Ataxia-telangiectasia
Quek, H., Luff, J., Cheung, K., Kozlov, S., Gatei, M., Lee, C. S., Bellingham, M., Noakes, P., Lim, Y. C., Barnett, N., Dingwall, S., Wolvetang, E., Mashimo, T., Roberts, T. and Lavin, M. (2016). Neuroinflammation drives the neuronal degenerative phenotype in a rat model of Ataxia-telangiectasia. International Congress of Immunology (ICI), Melbourne, Australia, Aug 21-26, 2016. Weinheim, Germany: Wiley - V C H Verlag GmbH & Co. KGaA. doi: 10.1002/eji.201670200
Stem Cell Therapies and Radiological Imaging in Ataxia Telangiectasia
Dingwall, Steven (2016). Stem Cell Therapies and Radiological Imaging in Ataxia Telangiectasia. PhD Thesis, School of Medicine, The University of Queensland. doi: 10.14264/uql.2016.822
Studying the basis of and developing new therapies to treat heart disease
(2023–2024) IPF Healthy - Medical Research