Projects per year
My research team seeks to increase the understanding of the underlying pathological mechanisms of disease focusing on Type 1 and 2 diabetes and diabetic complications of the cardiovascular and hepatic systems. We also research medicines opitization investigating cellular mechanisms of drug-induced complications.
Research on the complications of diabetes started in 2000 and I was part of the group that first identified the DNA repair enzyme poly (ADP-ribose) polymerase as a central mediator of diabetic cardiovascular complications. I have continued this work looking at the role of the glucose metabolite methylglyoxal and how dicarbonyl stress may play a key role in diabetic complications not just in the cardiovascular system but also in the hepatic and renal systems.
My other major research area stems from an interest in medicines optimization, we have investigated how the antiretroviral drugs used to successfully treat HIV increase the risk of these patients developing cardiovascular disease. We have identified poly (ADP-ribose) polymerase activation as a key mediator of antiretroviral-induced cardiovascular cell damage as well as investigating possible adjuvant therapies that may prove effective in protecting against this cellular damage.
Most recently we have started to develop an understanding on a cellular level of how the direct oral anticoagulant (DOAC) therapies such as Rivaroxaban and Apixaban may be causing dizziness and headaches necessitating their discontinuation in patients, this work may lead to improved patient screening and monitoring to optimize the appropriate therapy for patients. This work has been extended into drug-induced liver injury (DILI) to understand how the clinical observations of DOACs increasing the incidence of DILI is occuring on a cellular level.
Current research projects:
- Pathology of anti-retroviral drug-mediated cardiovascular, ß-cell, and hepatic complications
- Underlying mechanisms of diabetic complications observed in the cardiovascular and hepatic systems
- Direct Oral Anticoagulant-mediated complications of the cardiovascualrand hepatic systems.
- Pathological role of methylglyoxal in disease including ageing and Type 2 diabetes
Approach to teaching
I teach on a wide variety of courses including the Masters courses in Pharmacy and Clinical Pharmacy at the University of Brighton while also delivering material to medical students at the Brighton & Sussex Medical School. I am the indigestion case leader in the 1st year of the MPharm degree as well as being the module leader of the PY 367 Advanced Pharmacy 3 module as well as the PYM 06 Oxidative Stress special topic, roles that allow me to have a direct impact on the delivery of teaching material to the students.
In the early years of the degree my teaching underpins the basic concepts of organ function and control, pathologies that can disrupt normal function and the available pharmacological interventions that can correct these problems to improve patient morbidity and mortality. My specialized teaching focuses on providing students an understanding of metabolic pathways and how these are disrupted in diabetes and controlled using pharmacological agents.
My lecture material is developed from first principals coupled with interactive questions and supported by online video lecture material. In addition I run experimental practical sessions in the laboratory setting with students obtaining a hands on experience of concepts covered in traditional lectures. I am passionate about student feedback to ensure that they develop and improve their skill base as they move through the degree delivering specific feedback lectures on aspects of their coursework and laboratory performance. Teaching in the later years revolves around special topics and small group teaching where students are exposed to the latest scientific discoveries in recently published journal articles, and research projects where students work within my research group obtaining novel data in the area of diabetes and HIV medicine.
Dr. Jon Mabley is a Principal Lecturer and Student Engagement Champion in the School of Pharmacy & Biomolecular Sciences with research interests that focus on the pathophysiological implications of the complications of diabetes and HIV.
He was awarded his Pharmacology degree from University of Wales, College Cardiff in 1991 and his D.Phil. in Biochemistry from University of Sussex in 1996. His D.Phil. research focused on the pancreatic ß-cell and the protective effects of growth factors against cytokine-mediated dysfunction. He completed his post-doctoral training at the University of Kentucky USA studying the effects of saturated fatty acids on endothelial cell function as well as investigating the cardiovascular protective effects of estrogen.
In 1998 I was recruited to Inotek Pharmaceuticals in Boston USA as a pharmacologist before becoming Director of Pharmacology in 2002. During my time at Inotek Pharmaceuticals I carried out research in a wide variety of fields mainly focusing on the role the DNA repair enzyme Poly (ADP-ribose) polymerase (PARP) plays in pathological conditions. I was a leading member of the team that identified overactivation of PARP is a central mediator of diabetes-mediated cardiovascular complications, as well as implicating PARP in diseases such as colitis, ageing, inflammation, hemorrhagic shock, chronic heart failure, and ARDS. During this time I was also involved in researching the role of nitrergic, purinergic and cholinergic signaling in the pathology of inflammatory conditions.
In 2004 I joined the University of Brighton and have continued my research into the role PARP plays in diabetes and cardiovascular disease. In addition at Brighton I have extended my research into understanding the underlying cellular mechanisms responsible for drug-induced side effects focusing in particular on the anti-retroviral drugs used to treat HIV infection as well as the cellular process and molecules that may be involved in ageing.
My primary supervisory interest are in the field of diabetes both at the ß-cell level and complications in the cardiovascular and hepatic system. Projects currently running in my labortaory are looking at dicarbonyl stress-mediated diabetic complications and how anti-retroviral drugs can impact the pancreatic ß-cell. A secondary interest is in anti-retroviral drug-mediated cellular dysfunction looking at the possible molecular mechanisms underlying the adverse drug reactions observed with these therapies.
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- 1 Finished
Hypotensive effect of novel oral anticoagulant agents
1/01/15 → 31/12/18
Divergent effects of HIV reverse transcriptase inhibitors on pancreatic beta-cell function and survival: potential role of oxidative stress and mitochondrial dysfunctionMaandi, S. C., Maandi, M. T., Patel, A., Manville, R. & Mabley, J., 26 Jan 2022, In: Life Sciences. 294, p. 120329 120329.
Research output: Contribution to journal › Article › peer-reviewOpen Access
Damage to pancreatic INS-1E cells through impairment of mitochondrial function by the antiretroviral agents efavirenz and rilpivirineMaandi, S. C. & Mabley, J., 8 Dec 2020.
Research output: Contribution to conference › Abstract › peer-review
Enhancement of palmitate-induced lipotoxicity in INS-1E cells by the HIV medications efavirenz and rilpivirineMaandi, S. C. & Mabley, J., 25 Aug 2020.
Research output: Contribution to conference › Abstract › peer-reviewOpen Access
Investigation into the effects of HIV pre‐exposure prophylaxis (PrEP) agents Truvada® and rilpivirine on INS‐1E beta cell function and viabilityMaandi, S. C., Patel, A., Alsini, O. & Mabley, J., 7 Oct 2020, (Accepted/In press).
Research output: Contribution to conference › Abstract › peer-reviewOpen Access
Direct oral anticoagulant (DOAC)-mediated vasodilation: Role of nitric oxideMabley, J., Patel, J., Sayed, A., Arya, R. & Scutt, G., 12 Feb 2019, In: Thrombosis Research. 176, p. 36-38 3 p.
Research output: Contribution to journal › Letter › peer-reviewOpen AccessFile