"My laboratory aims to understand immune mechanisms of neural circuitry and function. Specifically, we study how synapses are targeted in the adult brain for elimination, and dissect pathways by which microglia contribute to region-specific synapse dysfunction in neurologic diseases such as Alzheimer’s and Parkinson’s diseases." Soyon Hong
UK DRI Group Leader
Dr Soyon Hong received her PhD in Neuroscience in 2012 from Harvard University and completed her post-doctoral fellowship at Boston Children’s Hospital and Harvard Medical School in 2018. While in this latter role, she conducted a study that was among the first to propose microglia as critical players in synaptic pathology in disease. She now brings these expertise and knowledge to establish a new UK DRI lab group at UCL.
1. At a glance
A breakdown in communication – microglia’s role in neurodegenerative disease
There are an estimated 850,000 people living with dementia in the UK. Alzheimer’s disease (AD) is the most common cause and is characterised by the widespread loss of connections - synapses - between neurons. Communication is essential to brain function and without these links, neurons begin to die, and clinical symptoms appear, such as memory loss. It is not clear how synapses are lost in AD, but scientists are finding evidence that other types of cells in the brain may be playing a critical role.
The major resident immune cells in the brain, microglia, are heavily implicated in this extensive loss of synapses in AD. During development, microglia sculpt this complex network of connections while maintaining the brain architecture throughout our lives. In a disease like AD, it is thought unknown changes with age or the introduction of a cellular stress (e.g. abnormal protein) alter the role of microglia, perhaps causing them to become dysfunctional and phagocytose (‘eat’) surrounding synapses.
Dr Soyon Hong is a specialist in the relationship between microglia and synapses, and her group is exploring these interactions in a disease context. Using cutting-edge microscopes and other tools, Soyon’s team will explore whether certain synapses are vulnerable, and whether different subsets of microglia become dysfunctional in disease. She aims for identification of mechanisms that could then be targeted by therapeutics.
2. Scientific goals
Recent genome-wide studies implicate microglia and immune-related pathways in Alzheimer’s disease (AD); however, the biological significance of these immune pathways is not well understood. Interestingly, it is becoming increasingly clear that microglia are active partners in brain wiring, in that they help shape the developing brain and aid the breakdown of synaptic circuitry in disease. Loss of synaptic integrity is a hallmark of AD and several other neurologic diseases.
During her postdoctoral period, Dr Soyon Hong was among the first to propose microglia as critical players in synaptic pathology in various disease models. These findings raise the need to understand the immune basis of neurologic function and circuitry. Several questions have emerged: Do microglia specifically phagocytose dysfunctional synapses? What cues regulate microglial pruning? What molecules, besides complement, are utilised in neuroglial communication? The pathological functions of microglia reveal a need to fully understand what microglia do in the healthy adult brain and how they become dysfunctional with, or contribute to, ageing and dementia.
Soyon’s research will broaden our understanding of how different cell types work together to maintain brain function, and how these interactions may go awry during ageing and dementia. Furthermore, the goal will be to extend this into translational research relevant to humans. As region-specific vulnerability is a hallmark of many neurodegenerative diseases, the proposed experiments have the potential to reveal mechanistic insight in a variety of neurological diseases.
Main objectives and research goals:
In Soyon’s UK DRI programme, she aims to address these questions from several unique angles:
1. Investigate molecular pathways that target synapses for elimination in models of Alzheimer’s disease, Parkinson’s disease, FTD/ALS and others, and determine whether microglia confer region-specific synaptic and neuronal dysfunction.
2. Study whether and how microglia contribute to higher cognitive functions, i.e. learning and memory.
3. Increase understanding of how adaptive immune signalling contributes to neuroglial interactions in the adult brain, in the context of normal ageing and neurodegenerative diseases.
Statement on teaching and mentorship
"I have mentored and taught many students and technicians through lectures and laboratory settings (26 mentees in laboratory settings to date). I highly value the opportunities to mentor. It is one aspect of my career that I find truly rewarding. I believe that having a positive, stimulating environment where trainees are valued is key to having a productive and creative lab. Trainees who join my laboratory will be trained in cellular and molecular biology including neuroscience and neuroimmunology. Moreover, they will be mentored to be independent critical thinkers, a core of my teaching philosophy."
3. Team members
Dr Sang-Eun Lee (Postdoctoral Researcher)
Dr Sebastiaan De Schepper (Postdoctoral Researcher)
Dr Javier Rueda-Carrasco (Postdoctoral Researcher)
Dr Julie Rebejac (Postdoctoral Researcher)
Gerard Crowley (PhD Student, Wellcome Neuroscience PhD Programme)
Dimitra Sokolova (PhD Student, CASE BBSRC PhD Programme)
Saadia Hasan (PhD Student, NIH-UCL Graduate Partnership Program)
Maria Yudina (PhD Student - joint with Dr Tim Bartels)
Christina Maat (PhD Student)
Francesca Puletti (PhD Student)
Judy Ge (Research Assistant)
Lais Sousa Da Silva Ferreira (Research Assistant)
Viktoras Konstantellos (Research Assistant)
Sophie Paschke (Research Assistant)
Zara Kaplan (Student)
Shari Addington Ghansah (Student)
Kaja Posnik (Visiting Student)
Giulia Ramella (Visiting Student)
Yongjing Zheng (Visiting Student)
Nicholas Monaco (Taught Student)
4. Collaborations
Within UK DRI:
- Prof Adrian Isaacs, UK DRI at UCL
- Dr Tim Bartels, UK DRI at UCL
- Prof Tara Spires-Jones, UK DRI at Edinburgh
- Dr Frances Wiseman, UK DRI at UCL
- Prof Dario Alessi, UK DRI Associate Member, MRC PPU, University of Dundee
Beyond UK DRI:
- Prof Kenneth Harris, UCL
- Dr Michael Ward, NIH
- Dr Andrew Macaskill, UCL
- Prof Hugh Willison, Glasgow
5. Topics
Microglia, astrocytes, synaptopathy, neuroinflammation, complement, neuroimmune
6. Techniques
Structured Illumination Microscopy (SIM), STED, immunohistochemistry, confocal microscopy, spatial transcriptomics, single cell transcriptomics
7. Key publications
Rueda-Carrasco J*, Sokolova D*, Lee SE*, Childs T, Jurčáková N, De Schepper S, Ge JZ, Lachica JI, Toomey CE, Freeman OJ, Hardy J, Barnes SJ, Lashley T, Stevens B, Chang S, Hong S. (2023) EMBO Journal Microglia target synapses with externalized phosphatidylserine to ameliorate neuronal hyperactivity. https://www.embopress.org/doi/...
De Schepper S, Ge JZ, Crowley G, Ferreira LSS, Garceau D, Toomey C, Sokolova D, Rueda-Carrasco J, Shin SH, Kim JS, Childs T, Lashley T, Burden JJ, Sasner M, Sala Frigerio C, Jung S, Hong S. (2023) Nature Neuroscience Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer’s disease. doi: 10.1038/s41593-023-01257-z
Sokolova D, Childs T, Hong S. (2021) Insight into the role of phosphatidylserine in complement-mediated synapse loss in Alzheimer’s disease. Faculty Reviews. 10.12703/r/10-19.
Bartels T, De Schepper S, Hong S. (2020) Microglia modulate neurodegeneration in Alzheimer‘s and Parkinson’s diseases. Science. 10.1126/science.abb8587.
De Schepper S, Crowley G, Hong S. (2020) Understanding microglial diversity and implications for neuronal function in health and disease. Dev Neurobiol. 10.1002/dneu.22777.
Shi Q, Chowdhury S, Ma R, Le KX, Hong S, Caldarone BJ, Stevens B, Lemere CA. Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice. (2017) Sci Transl Med.
Hong S, Nfonoyim BM, Beja-Glasser VF, Frouin A, Li S, Ramakrishnan S, Merry KM, Shi Q, Rosenthal A, Barres BA, Lemere CA, Selkoe DJ, Stevens B. (2016) Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science. doi: 10.1126/science.aad8373.
Hong S, Ostaszewski BL, Yang T, O’Malley TT, Jin M, Yanagisawa K, Li S, Bartels T & Selkoe DJ. Soluble Aβ oligomers are rapidly sequestered from brain ISF in vivo and bind GM1 ganglioside on cellular membranes. Neuron. 2014 Apr 16;82(2):308-19. PMC4129520. Epub 2014 Mar 27.
