Dr Ilse Pienaar

Dr Ilse Pienaar

Institute of Clinical Sciences
Associate Professor in Pharmacology

Contact details

Address
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Qualifications

  • Certificate in Advanced Studies in Academic Practice (CASAP); Fellowship with the Higher Education Academy (HEA)
  • PhD in Neurophysiology
  • MSc in Neuroscience
  • BSc (Hons) in Clinical Pharmacology  * A second undergraduate degree
  • BSc (Hons) in Molecular and Cell Biology

Biography

Ilse completed an undergraduate degree in Molecular Cell Biology, followed by an MSc in Neuroscience and then a PhD in Neurophysiology at Stellenbosch University in South Africa, for which she spent extensive research visiting times at a collaborating lab at Oxford. She was subsequently awarded the Rita Levi-Montalcini Post-Doctoral Fellowship from the International Brain Research Organisation (IBRO) which Ilse used to conduct post-doctoral work at the MRC Functional Genomics and also the MRC Neuropharmacology Units at Oxford University. This was followed by a post-doctoral position in the Mitochondrial Research Centre at Newcastle University, under supervision of Professor Sir Doug Turnbull, and then an independent Research Fellowship awarded by Imperial College London, subsequently followed by faculty positions at Northumbria University and then the University Sussex, where she was promoted to a Senior Lecturer in Pharmacology.

Ilse's research concerns the molecular-cellular causes and druggable targets of the synucleinopathy disorders, where her lab tries to find unique molecular-genomic signatures between the different disorders that fall under this disease umbrella term and also addresses the issue of how the pathologies of different neurochemical neuronal types differ, even though they all undergo cell death in these disorders. The ultimate aim of this work is to design novel and improve existing therapies to be able to target specific neuronal types to correct their unique pathological signature, and also for developing therapies that are disease specific and hence more effective.

Ilse is currently Co-Investigator on a £300k+ British Heart Foundation project - Investigating a novel mechanism underlying increased risk of vascular events in Parkinson’s disease: Dissecting pathological synergy between protein aggregates and glycosaminoglycans (PG/22/11143).

Teaching

Ilse delivers tutorials, seminars, workshops and lectures across a range of modules.

Postgraduate supervision

Ilse supervises undergraduate final year, MSc and mRes research projects.  She has supervised several PhDs to completion and currently serves as supervisor for a number of PhD students at the University of Birmingham and as an honorary supervisor at other UK universities.

Research

Ilse's research relates to deconstructing the molecular signalling, 'type' specific neuronal (focusing particularly on acetylcholine-producing - so-called cholinergic neurons) and related circuitry therapeutic targets of neurodegenerative diseases, with particular emphasis on Parkinson’s disease (PD) and Lewy Body Dementia (LBD), but also holding several collaborations with Alzheimer’s disease (AD) researchers. Research in her lab encompasses three main themes:

(1) Ilse's lab has been instrumental in characterizing innovative, clinically relevant animal models of PD. To such models of disease, she applies in vivo neuromodulation using Designer Receptors Exclusively Activated by Designer Ligands (DREADDs), encompassing viral vector-mediated targeting for activating/inhibiting signaling activity of genetically-defined cells (encompassing specific neurochemical cell ‘types’). As engineered G-protein coupled receptors (GPCRs), DREADDs precisely control three major GPCR signaling pathways (Gq, Gi, and Gs) in vivo. DREADDs hold immense translational promise, due to their non-invasiveness, DREADD ligands’ high brain penetration and precision medicine ability. The design space for neuromodulation technology remains unbounded as we lack a clear understanding of which neural elements to target for improving each symptom. Ultimately, the aim of Ilse's research is to develop new types of cell- and pathway-specific stimulation strategies that are GPCR-based, thereby developing and refining neural interface technologies to improve the quality of life for people with neurodegenerative disease.

(2) On the theme of developing compounds capable of restoring neurodegenerative disease-induced aberrant cellular metabolism, Ilse collaborates extensively with medicinal chemists at UK and international universities, to evaluate the ability of novel and repurposed compounds, for example to reduce pathological iron levels and hence decrease mitochondria-derived oxidative stress. Specifically, elevated brain iron is believed to cause (or greatly contribute) to neuronal loss in age-related neurodegeneration. Ilse collaborates with various organic chemists who design novel iron chelators capable of avoiding common-side effects associated with clinically available iron chelators and apply innovative methods to allow compounds to cross the blood-brain barrier in therapeutic sufficient concentrations.

(3) A further theme in Ilse's research is understanding how, at single cell resolution, the mitochondrial genome is affected by neurodegenerative disease, for identifying novel drug targets. In particular, she interrogates mitochondrial contributions towards rendering certain brain cell-types vulnerable to age-related disease, whilst sparing others. For this, her lab applies specialist single cell mitochondrial genetic assays (e.g. mitochondrial copy number) and mitochondrial whole-genome sequencing platforms, to identify molecular-genetic clues from human post-mortem brain samples.

Ilse is currently Co-Investigator on a £300k+ British Heart Foundation project - Investigating a novel mechanism underlying increased risk of vascular events in Parkinson’s disease: Dissecting pathological synergy between protein aggregates and glycosaminoglycans (PG/22/11143).

Publications

Recent publications

Article

Sigurdsson, H, Hunter, H, Alcock, L, Wilson, R, Pienaar, I, Want, E, Baker, M, Taylor, J-P, Rochester, L & Yarnall, A 2023, 'Safety and tolerability of adjunct non-invasive vagus nerve stimulation in people with parkinson’s: a study protocol', BMC Neurology, vol. 23, no. 1, 58. https://doi.org/10.1186/s12883-023-03081-1

Fouché, B, Turner, S, Gorham, R, Stephenson, EJ, Gutbier, S, Elson, JL, García-Beltrán, O, Van der westhuizen, FH & Pienaar, IS 2022, 'A novel mitochondria-targeting iron chelator neuroprotects multimodally via HIF-1 modulation against a mitochondrial toxin in a dopaminergic cell model of Parkinson's disease.', Molecular Neurobiology. https://doi.org/10.1007/s12035-022-03107-8

Wong, J, Steyn, JS, Pienaar, I & Elson, JL 2022, 'Mitochondrial DNA population variation is not associated with Alzheimer's in the Japanese population: a consistent finding across global populations', PLOS One, vol. 17, no. 10, e0276169, pp. e0276169. https://doi.org/10.1371/journal.pone.0276169

Müller-Nedebock, AC, Pfaff, AL, Pienaar, I, Koks, S, van der Westhuizen, FH, Elson, JL & Bardien, S 2022, 'Mitochondrial DNA variation in Parkinson’s disease: analysis of “out-of-place” population variants as a risk factor', Frontiers in Aging Neuroscience, vol. 14, 921412. https://doi.org/10.3389/fnagi.2022.921412

Lewis, F, Bird, K, Navarro, J-P, El Fallah, R, Brandel, J, Hubscher-Bruder, V, Tsatsanis, A, Duce, J, Tetard, D, Bourne, S, Maina, M & Pienaar, I 2022, 'Synthesis, physicochemical characterization and neuroprotective evaluation of novel 1-hydroxypyrazin-2(1 H)-one iron chelators in an in vitro cell model of Parkinson's disease.', Dalton Transactions, vol. 51, no. 9, pp. 3590-3603. https://doi.org/10.1039/d1dt02604f

Chapter (peer-reviewed)

Bailey, LJ, Elson, JL & Pienaar, I 2021, Single-cell approaches for studying the role of mitochondrial DNA in neurodegenerative disease. in V Weissig & M Edeas (eds), Mitochondrial Medicine: Volume 3: Manipulating Mitochondria and Disease- Specific Approaches. 2 edn, Methods in molecular biology (Clifton, N.J.), vol. 2277, pp. 299-329. https://doi.org/10.1007/978-1-0716-1270-5_19

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