Dr Aoife Murray, Ph.D.

Profile

Following an undergraduate in Human Genetics at Trinity College Dublin, Aoife obtained her PhD in Medical Genetics from the University of Cambridge in 2013. She then took up a post-doctoral position with Prof. Dean Nizetic in Queen Mary, University of London, developing a world first isogenic human induced pluripotent stem cells (hiPSCs) model for the study of Down Syndrome and Alzheimer’s Disease. She participated also in the research conducted as part of The London Down Syndrome Consortium (LonDownS) funded by The Wellcome. She continued working with Prof. Nizetic at Lee Kong Chian School of Medicine in Singapore and in 2016 received a WHRI-ACADEMY/Marie Curie fellowship to develop technologies for enhancement of Down syndrome related cellular phenotypes using human induced pluripotent stem cells. Aoife recently moved back to London with a research fellowship from the Jérôme Lejeune Foundation to further examine the specific biological features of trisomy 21 neurons that affect cell-cell transmission of Alzheimer’s pathology using cerebral organoids.

Research

Research Interests:

My research interest is in understanding the genetic and functional links between Down Syndrome and Alzheimer’s Disease.

Assessment of specific biological features of trisomy 21 neurons, affecting cell-cell transmission of Alzheimer’s pathology using cerebral organoids.

Individuals with Down Syndrome (DS) have an increased risk of developing Alzheimer’s Disease (AD), but a delay in the age of onset of AD compared to what would be expected based on what we know about the genetics of AD. This suggests there are biological mechanisms in trisomy 21 (T21) brain cells (neurons) that can protect or alter how AD impacts the neurons, and how the disease spreads through the brain.

We have recently developed a human cellular model that starts from skin or hair follicle cells donated by a person with DS, whereby cells then get re-programmed into induced pluripotent stem cells, and these then driven to differentiate into brain cells. This allows us to model multiple aspects of AD pathology (amyloid plaques, aggregated Tau and neuronal cell death) in T21 cerebral organoids. The proposed project would use this model to examine how AD pathology spreads from neuron to neuron, and if this is different between T21 and control disomy 21 (D21) cells.

Understanding biological processes in neurons that delay AD onset in people with DS could be exploited as a protective/therapeutic strategy for AD, both for individuals with DS and for the general population.

Publications

Key Publications

Aoife Murray^#c, Gillian Gough^#, Ana Cindrić^#, Frano Vučković^#, David Koschut, Vincenzo Borelli, Dražen J. Petrović, Ana Bekavac, Ante Plećaš, Valentina Hribljan, Reinhard Brunmeir, Julija Jurić, Maja Pučić-Baković, Anita Slana, Helena Deriš, Azra Frkatović, Jűrgen Groet, Niamh L. O’Brien, Hong Yu Chen, Yee Jie Yeap, Frederic Delom, Steven Havlicek, Luke Gammon, Sarah Hamburg, Carla Startin, Hana D’Souza, Dinko Mitrečić, Mijana Kero, Ljubica Odak, Božo Krušlin, Željka Krsnik, Ivica Kostović, Jia Nee Foo, Yuin-Han Loh, Norris Ray Dunn, Susana de la Luna, Tim Spector, Ingeborg Barišić, Michael S.C. Thomas, Andre Strydom, Claudio Franceschi, Gordan Lauc*, Jasminka Krištić*^c, Ivan Alić*^c , Dean Nižetić*^c (2023)
Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels.
eBioMedicine. Published: July 12, 2023, DOI:https://doi.org/10.1016/j.ebiom.2023.104692
#These authors contributed equally (shared first authors), *These authors jointly supervised work (joint senior authors), ^cCo-Corresponding authors.

Ivan Alić*, Pollyanna A Goh*, Aoife Murray*, Erik Portelius*, Eleni Gkanatsiou, Gillian Gough, Kin Y Mok, David Koschut, Reinhard Brunmeir, Yee Jie Yeap, Niamh L O’Brien, Jurgen Groet, Xiaowei Shao, Steven Havlicek, N Ray Dunn, Hlin Kvartsberg, Gunnar Brinkmalm, Rosalyn Hithersay, Carla Startin Sarah Hamburg, David Wallon, Anne Rovelet-Lecrux, Hilkka Soininen, Emanuela Volpi, Joanne E Martin, Jia Nee Foo, David L Becker, Agueda Rostagno, Jorge Ghiso, Željka Krsnik, Goran Šimić, Ivica Kostović, Dinko Mitrečić, LonDownS Consortium, Paul T Francis, Kaj Blennow, Andre Strydom, John Hardy, Henrik Zetterberg & Dean Nižetić. (2020).
Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain. 
Molecular Psychiatry. Epub 10^th July 2020, https://doi.org/10.1038/s41380-020-0806-5 
*these authors contributed equally as first author and are listed in alphabetical order

Gillian Gough, Niamh L. O’Brien, Ivan Alic, Pollyanna A. Goh, Yeap Yee Jie, Jurgen Groet, Dean Nizetic & Aoife Murray (2019)
Chapter 4. Modelling Down syndrome in cells: from stem cells to organoids.
Progress in Brain Research, Volume 251: 55-90, Preclinical Research in Down syndrome: From Bench to Bedside. Available online 20^th November 2019. ISSN 0079-6123. Serial Volume Editor: Mara Dierssen

Chooi WH, Ong W, Murray A, Lin J, Nizetic D, Chew SY (2018)
Scaffold mediated gene knockdown for neuronal differentiation of human neural progenitor cells. 
Biomaterials Science 6(11): 3019-3029. PMID: 30277233

Aoife Murray, Audrey Letourneau, Claudia Canzonetta, Elisavet Stathaki, Stefania Gimelli, Frederique Sloan-Bena, Robert Abrehart, Pollyanna Goh, Shuhui Lim, Chiara Baldo, Franca Dagna-Bricarelli, Saad Hannan, Martin Mortensen, David Ballard, Denise Syndercombe Court, Noemi Fusaki, Mamoru Hasegawa, Trevor G. Smart, Cleo Bishop, Stylianos E. Antonarakis, Jürgen Groet, & Dean Nizetic (2015).
Isogenic induced pluripotent stem cell lines from an adult with mosaic Down Syndrome model accelerated neuronal ageing and neurodegeneration. 
Stem Cells, 33(6):2077-84. PMID: 25694335

Sergey I. Nikolaev, Marco Garieri, Federico Santoni, Emilie Falconnet, Pascale Ribaux,  Michel Guipponi, Aoife Murray, Jürgen Groet, Emanuela Giarin, Giuseppe Basso, Dean Nizetic & Stylianos E. Antonarakis (2014).
Frequent cases of RAS-mutated Down syndrome acute lymphoblastic leukaemia lack JAK2 mutations.
Nature Communications 5:4654. PMID: 25105841