KA: Johanna, thank you for taking time for this interview. To start with, tell us a little bit about your career background and research interest.
JJ: I actually did my PhD at Imperial College. The focus of my project was imaging in a Parkinson’s Disease model, looking at stem cells and whether they increase dopamine levels after transplantation. I then went to Sweden and did postdoctoral research, looking at neurogenesis in epilepsy and synaptic integration - so how the newly formed cells integrated with the mature granule cells. I then came back to the UK and briefly worked at the Hammersmith site of Imperial college with Vincenzo De Paola, looking at axonal degeneration in an axonal injury mouse model. As the funding for this project came to an end, I left to work at Eli Lilly - the pharmaceutical company. They were looking for a postdoc to set up in vivo two-photon imaging facility to look at synaptic loss in Alzheimer’s disease (AD) models. I was offered a permanent position as a research scientist, which was great as I ended up having my own group and staying there for eight years. While leading my own team there, I did some drug discovery work as well as investigating the synapse loss in AD models. Things then changed a bit and my group's focus changed slightly. At the beginning of last year I decided that I was no longer doing the science that I enjoyed and so I decided to leave. My next position was my current role at the UK Dementia Research Institute (UK DRI) at Imperial.
KA: Very impressive career path and clearly influenced and driven by your interest in synapses. You are leading the Multi- ‘Omics Atlas Project at the UK DRI, what does the project involve and why do we need it in AD field?
JJ: Yes, I’m leading the Multi- ‘omics Atlas Project. But alongside that, I'm starting to carve out my own work based on my scientific interests as well. The Multi- ‘omics Atlas Project is a UK DRI directors’ initiative. We will comprehensively map the disease pathology that occurs in human AD in different brain regions, across different cell types and at different stages of the disease. So, what this entails is, we will be doing routine histopathology, which has been done for decades on Alzheimer's brain tissue. But we will also bring in the multi-omics approach and that means we will collect data at the epigenetic level, the genetic level, transcriptomic, proteomic, up to the lipidomic data level. And then, importantly, we will bring it all together using bioinformatics, which is a large component of this project. We need this approach because, although these things have been done before to a certain extent, they have been done separately, so not actually brought together to have a really comprehensive understanding of the human AD condition. This is all done on a post-mortem human brain tissue and hopefully it will lead to a greater understanding of the disease state and the disease progression.
KA: Having an in-depth understanding of the disease and its progression will definitely help us develop disease-modifying strategies so that is a very exciting project. You mentioned that alongside this you are also carving your own scientific research. Is that focusing on synapses or are you moving into a different direction?
JJ: Yeah, so it is still largely in synapse space. Within the multi Multi-‘omics Atlas Project, there is a synapse component and that is the part that I am leading. I also co-supervise a PhD student who is looking at synaptic vulnerability in AD.
KA: We know that Alzheimer’s is a very complex and multifaceted disease and as we discussed earlier, there are many components of the brain that we should look at to really understand the pathology. But, why are synapses particularly important in AD?
JJ: Well, I think one thing that isn't really known at the moment is how and why the synapse loss occurs in Alzheimer's. There’s evidence that it’s tau driven or that the loss of synapses occurs around Amyloid plaques, but exactly what the mechanism is, still needs to be better understood and investigated in more detail, especially in humans. This is particularly important when developing disease modifying interventions. So, [putting my drug discovery hat on] let’s say you are delivering a drug which is thought to modify the underlying pathology, for example, tau or amyloid, or potentially inflammation, does that have a knock on effect and prevent the synapses being lost? Maybe it does not and so it has no effect on the synapse loss and therefore does not improve cognition. When I was at Lilly, we were looking at if we can target the synapses directly to prevent them from being lost or even their ability to regenerate. Targeting synapses could have a direct impact on the condition of the patients.
KA: For that, one would need to look at synapses in living patients. What are some of the current methods to image synapses in AD patients?
JJ: It is really tricky and one of the exciting developments in the field is the discovery of SV2A PET tracer. It is still in development, but it has great potential for clinical applications to monitor the synaptic density and synaptic health. It is only on the pre-synaptic level, and so does not give us information on what is happening post-synaptically, but it is the best tracer that we have at the moment. Imaging synapses in living individuals is very challenging and that has really held the field back up until now, so these discoveries are very exciting.
