PARKINSON'S DISEASE & MOLECULAR THERAPEUTICS

Parkinson’s disease is a brain disease that affects 1% of people over 65 years. This amounts to 1.2 million people in Europe and this number is expected to double by 2030 as people are living longer. Parkinson’s disease leads to affected individuals being unable to move, which has a significant impact on their quality of life. Moreover in the late stages of the disease, there is memory decline and many other so called non-motor symptoms.  The motor symptoms of Parkinson’s or the difficulties with movements are caused by the death of a group of nerve cells (neurons) in the brain that produce dopamine. While drugs that are currently available can for a time treat the symptoms of the disease, they do not stop its progression. Furthermore the effectiveness of these drugs wears off over time and if they are used for a long time lead to disabling side effects. Thus there is a critical need to develop new drugs for Parkinson’s.

We have on-going work aiming to characterise the fundamental mechanisms that regulate the survival and growth of dopaminergic neurons during development, and then to translate this information in new therapies that protect dopaminergic neurons from degeneration using viral vector-based and small molecule drug therapies.

FETAL PROGRAMMING & NEURODEVELOPMENTAL OUTCOMES

One of the topics we are interested in is 'fetal programming' of future brain health. Specifically we are interested in understanding how stress and inflammation in pregnancy affects the developing fetal brain and what are the consequences of this for brain performance and function later in life. Over the last number of years we have identified a "developmental window" of sensitivity of fetal neurons to inflammation. Essentially this means that during certain stages of pregnancy, neurons are more sensitive to inflammatory signals than at other stages. This is important as in humans inflammation is a common feature of a range of pregnancy complications including infection, stress, pre-eclampsia and others. Therefore understanding how inflammation affects the developing fetal brain, and understanding the implication of this for brain function in childhood, adolescent and adulthood is an important question.

​We are examining the molecular mechanisms that regulate normal fetal brain development, how these mechanisms are affected by common complications of pregnancy, including stress, hypoxia and infection, and what are the implications for neurodevelopmental outcomes such as ASD and ADHD in affected offspring.

SYMPATHETIC DEVELOPMENT AND DIFFERENTIATION

Neuroblastoma (NB) is a developmental malignancy that arises in the neuronal ganglia or adrenal medulla of the peripheral sympathetic nervous system. Specifically, it arises from undifferentiated neural crest progenitor cells that develop into the sympathetic nervous system. NB the most common cancer in babies younger than one year old and patients with high-risk disease characterised by amplification to the MYCN gene (~50 % of all NB new cases) require aggressive treatment including a combination of: chemotherapy, surgery, radiotherapy and biologic and immunotherapy. However 1 in 2 children do not survive. In those that do survive, a significant number suffer relapses with treatment resistant tumors and eventually succumb to the disease. For this reason there is a critical need to identify new drugs and drug targets for treatment-resistant NB. NB has been linked to a failure in neuritogenesis which is a key phase of neuronal differentiation during development

We have on-going work aiming to characterise the fundamental mechanisms that regulate the development and differentiation of sympathetic neurons during development, and in the development of small molecule drugs as molecular therapies for neuroblastoma.

SCHOLARSHIP OF TEACHING AND LEARNING

Authentic learning pedagogy centers around the context of situating learning tasks in the context of future use. This relates to addressing the gap that often exists in professional education between information and its application. In other words there is often a disconnect between theory and practice. As the disciplinary level, our research interests in this area are in the application of the Teaching for Understanding framework to the development of novel pedagogies in medical and life science education to address this gap, and in assessing the impact of these change on student engagement and student learning.​

In addition I also work with the Centre for the Integration of Research, Teaching and Learning (CIRTL) as a CITRL fellow to advance the integration of Research, Teaching & Learning with colleagues in many disciplines across the University. Specifically the CIRTL is committed to fostering a community of practice in teaching & learning across the University. CIRTL Fellows have a strong research & pedagogical focus in their own disciplines and bring that strength to bear in advancing the integration of Research, Teaching & Learning in higher education.

O'Keeffe lab, University,

College Cork, Cork, Ireland

© 2018 O'Keeffe lab

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