Dr. Naomi Habib,

My name is Naomi Habib, and I'm associate professor at The Hebrew University of Jerusalem and part of the center for brain sciences. My lab focuses on aging-related pathologies such as Alzheimer's Disease and we're trying to understand the molecular mechanism of these diseases. So aging-related pathologies are a huge problem in our aging societies, and we have no effective treatments.
So this is really a great motivation for us to try and tackle these problems from a different perspective. In the past 30 years, the research in Alzheimer's Disease has been largely neuronal focused and what we're doing in the lab, we're trying to tackle this question from a different perspective, which is profiling the entire cellular environment in the brain, and how it's involved in the disease progression.
So what I mean by that is how all the different cell types in the brain and the interactions between them are promoting disease. And we believe that by looking at this problem from a different perspective, we might find new therapeutic interventions. The main technique we use in the lab is single nucleus RNA sequencing, which is actually a method I've developed during my postdoctoral studies.
And what it actually is, is measuring thousands of RNA molecules in individual cells and we do it in a high throughput and large scale manner, at the end, we measure hundreds of thousands of cell from a given tissue or from a couple of tissues. And the advantage of single nucleus RNA sequencing compared to more traditional RNA sequencing technologies is that in the traditional technologies, we measure everything in bulk or in the entire tissue.
It's very hard to associate later the molecular signatures to different cell types. And in the single-cell technology, we measure the RNAs in single cells, and then by using machine learning algorithms, we can then associate every molecular change to different cell types.
And another advantage of the single nucleus RNA sequencing compared to single-cell RNA sequencing is that we can apply it to complex tissues like the brain, which is really hard to dissociate. And also, we can apply it to frozen tissue, meaning we can go to brain banks, or we can access tissue that was collected in remote sites.
So, how do we use it in my lab? We take postmortem human tissue from brain banks of either healthy or sick individuals, specifically Alzheimer's Disease patients, and we, after performing the measurements, we can then build a map of the Alzheimer's brain, and compare it to the healthy brain.
Then we can see how each individual cell type is molecularly changing throughout the disease progression. And overall, we are building a model of how all these different cells are interacting the molecular level and contributing to the disease. In a recent study, we've conducted on mouse models of Alzheimer's Disease, we build a cellular map of the Alzheimer's brain.
And what these maps revealed was that actually astrocyte cells, which we weren't expecting to have such a dramatic shift in the Alzheimer's brain, had the most dramatic molecular changes. What we found is we found that these astrocyte cells were shifting to a new state that's specific to the disease which we call disease-associated astrocytes. And we now focus, in our study, on these very fascinating population of astrocytes because we think they might hold an incredible therapeutic potential.
I think in the next few years, we'll see a great advancement of our understanding of disease mechanism, and specifically in Alzheimer's Disease and other age-related pathologies. And to a great deal, this is because of the advancement of technology, and specifically the single cell and single nuclear RNA sequencing technology that enables us to build these very detailed maps of the brain in health and disease.