Type 1 diabetes is an auto-immune disease, where the immune system destroys its own pancreatic beta cells in structures known as islets. Beta cells produce insulin, a hormone that plays a critical role in regulating blood glucose levels, and the availability of glucose as an energy source for cells and tissues. The loss of beta cells (and hence insulin) results in high blood glucose levels. Treatment requires frequent blood glucose measurements throughout the day and life-long insulin injections. Alternatively, islets from a healthy donor may be used for transplantation. Limitations of donor-derived transplants include the need for organ donation, poor transplant survival and lifelong immunosuppressive drugs.
Despite treatment, patients with T1D are prone to serious life-threatening complications including ketoacidosis (acidification of the blood), kidney and vascular disease. A stem-cell derived regenerative treatment to grow new islets and transplant this back into patients using their own cells would allow for unlimited islets to be grown within a laboratory and eliminate the need for immunosuppressive drugs, increasing the availability and ease of transplantation to T1D patients. Treatment with stem cells derived from only 10mL of a patient’s own blood allows for a potential permanent cure by reducing adverse tissue rejection.
We propose the development of a stem cell derived “patch” containing insulin producing cells and both vascular and support cells. Transplantation of this patch at the appropriate dose will replace the function of damaged islets in type 1 diabetics, which would abolish the need for insulin administration and daily blood glucose measurements, enhancing the quality-of-life of T1D patients.Treating diabetics with scalable, clinically relevant stem-cell-derived pancreatic patches may effectively mitigate diabetes and drastically increase the number of lifesaving transplants to diabetic patients, offering a new type of regenerative treatment
Key Achievements
2024 SVI Rising Star Award
2023 Baker Heart and Diabetes Institute, Cardiac Biology and Disease research grant
2022 Frontiers in Pharmacology editorial board
2019 Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Garth McQueen young investigator award
Vascular Biology
As part of the Institute's O'Brien Department, our main research focus is generating human blood vessels for integration in various human tissues grown in the laboratory, including human skin and small pieces of human liver (liver organoids). We also study the structure and function of these lab-generated human tissues.
Lab head: Associate Professor Geraldine Mitchell Lab co-head: Dr Kiryu YapBrassington, K., Kanellakis, P., Toh, B., Bobik, A., & Kyaw, T. (2022) Crosstalk Between Cytotoxic CD8+ T cells and Stressed Cardiomyocytes Triggers Development of Interstitial Cardiac Fibrosis in Hypertensive Mouse Hearts. Frontiers in Immunology. Impact Factor 8.8, Top 10% of Immunology (21/204) journals. This immunology-based study defined the intricate, synergistic role of both CD4/CD8 T cells and hypertension in the pathogenesis of fibrotic heart failure.
Brassington, K., Selemidis, S., Bozinovski, S., & Vlahos, R. (2022) Chronic obstructive pulmonary disease and atherosclerosis, common mechanisms, and novel therapies. Clinical science (Lond), 136(6), 405–423. Impact Factor: 6, Top 6% of Medicine (179/2754) Journals. This invited review outlined the similarities in both the oxidative and inflammatory responses in the pathogenesis of lung disease and cardiovascular disease, whilst defining potential novel therapies for the treatment of cardiopulmonary diseases.
Brassington, K., Chan, S. M, De Luca, SN., Dobric, A., Selemidis, S., Bozinovski, S., & Vlahos, R. (2022) Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice. Clinical science (Lond), 136(8), 537–555.). This publication defined the pathogenic role of the immune system in worsening cardiovascular outcomes in influenza infected patients with lung disease and outlined a potential novel therapy for its treatment.
Brassington, K., Chan, S. M, Seow, H J., Dobric, A., Selemidis, S., Bozinovski, S., & Vlahos, R. (2021) Ebselen reduces cigarette smoke-induced vascular endothelial dysfunction in mice. British Journal of Pharmacology (BJP). Impact Factor 10, Top 2% of Pharmacology, Toxicology and Pharmaceutics (18/769) journals. This publication provided the first scientific evidence on the direct effect of cigarette smoking on vascular endothelial dysfunction and proof-of-concept data highlighting the therapeutic potential of antioxidant treatment for cardiovascular disease.
Brassington, K., Selemidis, S., Bozinovski, S., & Vlahos, R. (2019). New frontiers in the treatment of comorbid cardiovascular disease in chronic obstructive pulmonary disease. Clinical Sci (Lond), 133(7), 885-904. This invited review outlined a plausible mechanism driving cardiovascular disease in lung disease patients. The pathophysiology of COPD, the detrimental role of oxidant/antioxidant balance, systemic inflammation and the effectiveness of current pharmacological interventions were critically assessed.
https://orcid.org/0000-0001-5908-1114