Welcome to Texas Talk.

I'm Gilbert Garcia, opinion writer and columnist for the San Antonio Express-News.

On this show, we bring you one on one conversations with some of the most fascinating figures in Texas politics, sports, culture and business.

San Antonio's Dr. Jennie Hsieh is at the forefront The exciting advances that are currently happening in brain research.

A neuroscientist who serves as a director of UTSA Brain Health Consortium, she's leading a team of researchers into groundbreaking lab studies into the causes and potential treatments for Alzheimer's disease and epilepsy.

On this episode, she talks about her lifelong fascination with the human brain, why the issue of Alzheimer's is so personal for her and what we can all hope to learn in the coming years about how the brain functions.

Let's get started.

Dr. Hsieh, thank you so much for being on Texas Talk.

Thank you for having me.

I'm delighted to be here.

Well, I know that you've had a fascination with the human brain for most of your life.

I wondered if if there was a particular anything in particular that kind of sparked that interest in.

And when you it became clear to you that this was something that you could maybe actually devote your career to.

Thank you for this question.

My when I was a high school student, I think when I look back, my favorite class was biology.

And even before I started being interested in the brain, I was always really interested in cells.

I thought that cells were the most fascinating things that were alive in this world, that cells are like little tiny cities inside the cells.

There are.

Everything is organized, starting from the instructions of the.

What makes the cell.

A cell comes from the genes.

And I was really interested in what genetic properties that control the cells.

And that's what really got me into the brain, because the most interesting cell of all is the stem cell.

And I learned later on in school that stem cells, there are stem cells in the brain.

And I wanted to start working on that and became more interested in that.

And that's a lot of the work that you're doing now with the Brain Health Consortium involves stem cells.

That's right.

That's right.

So so cells are the reason why I think stem cells are so interesting is because how do you go from a single cell to the hundreds and millions of cells in the body?

And the the fact that there are still stem cells in the brain?

I thought maybe this is a way to use them to understand how we could repair cells that are injured or dying in various neurological disorders like Alzheimer's and epilepsy.

A major focus of the work you're doing is Alzheimer's.

You've talked about the fact that your grandmother suffered from dementia in her later years.

What effect did this have on you and how did it affect the way you approach the research you've been doing?

Yes, the Brain Health Consortium, we thought this could be a great way to have scientists working together across a variety of disciplines, from neuroscience to using cell stem cells and precision medicine and working together with biomedical engineers and people who also study psychology in the in the in the human mind, working with patients, for example, patients with Alzheimer's or patients with autism.

And you mentioned my grandmother.

Certainly I think my she was the one who raised me.

So my when we came to America from originally from Taiwan, my mom had to work, my dad had to work.

So my grandmother lived with us.

And when she when she was younger, she was very active.

But I noticed that as soon as she got older and use less of her body physically, her brain also started to deteriorate.

And and that another one of the conditions we also study is epilepsy.

And so that even occurs could occur to people as they age, but also occur during childhood.

And so having those personal connections really most help motivate me to want to dive in deeper to understand the brain.

2013 The Obama administration launched the National Institutes of Health's Brain initiative, which was, I think, the really ambitious attempt to try to advance to foster brain research and advance that cause people compared it to like the moon shot of the 1960s.

What effect, if any, has it had on the work that you've done and what you've seen happening in the field of brain research since then?

So that was a really important initiative that President Obama launched the BRAIN initiative and the part of the goal is that really to get this interdisciplinary way of doing brain research, going to kick starting with this additional funding.

And, you know, we we've scientists have worked on the brain for many, many years and mostly by themselves.

And what we realize is that it really takes a team approach to understand something as complex as the human brain.

And what we also needed is more tools and more technologies.

And sometimes these tools and technologies aren't found within the field of neuroscience itself.

So what we really needed to do is take a step back and ask based on these more challenging types of questions and problems, what are the tools and technologies we really need to develop and and get various scientists coming from different disciplines to work together.

And that's really what the BRAIN initiative was all about.

And provided that level of continued funding and we were fortunate.

A few years after launching the Brain Health Consortium, a team of our scientists were able to secure one of these large multidisciplinary brain initiative grants.

Now you've talked about the challenges involved in studying the human brain, and we were dealing with something that's encased in a hard skull.

It's it's not it's it's not an easy thing to be able to to work with you.

I guess a lot of the work that you do involves surrogates for the human brain, you know, with its laboratory mice, baboons, is that is that still the case?

That's that's absolutely right.

As you mentioned, the the human brain is in a skull.

It's largely inaccessible.

There are times when if a patient is undergoing surgery.

Sometimes prior to surgery, neurosurgeons can probe the brain in a live human brain setting, sort of during that pre pre surgical phase for epilepsy surgery.

But only at that point is is when people might be able to see exactly what's going on.

So most of the time, the human brain is inaccessible.

And as you mentioned, a lot of our scientific work relies on surrogates.

We call them models and and models of the human brain.

We use rodent models.

So in the rodent, like, for example, the mouse model is very amenable to modeling because we could manipulate the cells and the molecules.

We can design certain genes or even make transgenic mice.

And that's been very powerful.

But one of the limitations of mouse models is that, as you know, the mouse is not a tiny human human.

So so that's why I'm very excited.

One of the sort of the new breakthrough technologies is to actually be able to make a stem cell line from a human patient.

And this person, personalized model, we hope can be complementary to some of these differences that we are maybe missing from a rodent model.

As far as work on Alzheimer's.

You know, there's so much more societal awareness of Alzheimer's than there was decades ago.

And I, I don't know what the numbers are.

I wonder if if we've seen an increase in cases of Alzheimer's or whether maybe there's just it's something that's just talked about more.

Do you have any sense about that, whether that this is something that is becoming more prevalent or it's just something that's that's discussed more?

We know that one of the biggest risk factors to developing Alzheimer's and dementia is aging.

And and we also know that as our human population is aging, there, certainly there's going to be a rise in the the numbers of individuals diagnosed with Alzheimer's.

I think some of it is doing to better diagnosis as well, and more public knowledge about the disorder so that that patients could also advocate for earlier screening.

But we also don't really know a lot about what causes and the underlying routes to developing Alzheimer's.

And one of the recent scientific studies is suggesting that genetic background and even epigenetic changes things in your environment could influence your likelihood or risk for developing Alzheimer's.

In fact, where we're seeing that, it seems to start as very early, perhaps even early in development.

Well, I was going to ask you about that.

But when you talk about environmental factors, you know, I grew up in the Randi Valley.

I read something a few months ago about how if if I understood the numbers correctly, that that incidence of Alzheimer's for people 65 and over were twice the national average or something along those lines.

And I couldn't help but think about potential environmental factors.

I mean, I know these things are there's probably a lot that we have to learn about things like that.

Right, right, right.

There's environmental factors.

There's also I think some of the data was suggests that even various socio economic factors to contribute to this.

And then another thing is there's also health disparities, for example, even genetic background.

And and historically, many of our studies of Alzheimer's have been done in more sort of in sort of less diverse populations.

And as you probably know, the risk of dementia is slightly increased for for individuals coming from like a Hispanic or Latino background.

And and that's very interesting and that's something that's concerning for us here in in San Antonio.

So one of the areas that myself and our collaborators at UT Health were working on is trying to understand why that is, you know, what is the biological basis for this.

And in fact, we're very excited to be able to use some of these personalized stem cell approaches to try to tackle this.

Question.

You were talking about early brain development, and I wrote about research or findings that come from from your lab that, if I understand correctly, they indicate that there is sound Alzheimer's and early brain development, which, you know, we tend to think of Alzheimer's as being the product of loss of neurons, the cells that process and transmit information, loss of neurons as people get older.

But if I understand what you all are finding, it's that it you're looking at the possibility that people have fewer neurons very early in their life.

And that and so this is something that's really that's there possibly from the beginning of life.

Is that that an accurate depiction of what you all do?

Yes.

So so so one of the things that's important to to sort of to think about is that Alzheimer's can the vast majority of Alzheimer's is sporadic Alzheimer's.

So that means it's sort of there's a combination of maybe your genes, probably your environmental factors.

And and maybe there's something else that we just don't know.

But there is a very small percentage of Alzheimer's that we call familial Alzheimer's, which is due to mutations in three genes and in individuals with those familial mutations, which is very rare in those individuals.

Alzheimer's can start earlier, for example, in their forties.

And so what one of the studies that my lab, my research lab has recently done is to use to study stem cells and specifically these brain organoids which are cell culture models of human brain development in a dish carrying one of these particular familial mutations.

And so we isolate all of the other variables like environment, diet, things of that nature.

And we just look to see what happens with the development of these cells, with these particular familial genetic mutations.

And as you point out, what we found in these organoid models is they seem to start with fewer neurons.

So it might be it's rare and it suggests these data suggest that possibly if patients have those same mutations, they might start with fewer neurons earlier in their life.

I'm sure that would lead to a different type of treatment approach, or the possibility at least exploring treating people earlier in their life.

Or how would what do you think this is going to lead?

Exactly.

I, I, we think that there could be two possible implications would be earlier screening, potentially earlier diagnosis, sort of not just akin to some of our studies with neurodevelopmental disorders where we would study or follow patients from infancy to childhood and in adolescence.

Perhaps we should also think about neurodegenerative disorders, as you know, following patients as earlier as well.

And then the second possibility is this could open up avenues for therapeutic strategies or finding therapeutic targets in a different way using these cellular brain organoid models as potentially a way to screen for new drugs.

I know embryonic stem cells are particularly valuable to research because they can become any type of cell in the body, and adult stem cells are more limited.

But obviously the politics surrounding the use of embryonic stem cells has been problematic.

It's been controversial over the years.

My understanding is that with your lab, you all have been able to reprogram adult stem cells to make them resemble or act in the way that that embryonic stem cells function is that you're.

That's almost right.

Okay, I'll take that.

But you're you're absolutely right to point out that there are adult stem cells like one of the my favorite ones that we study are the adult neural stem cell.

And that's naturally found deep within our brains.

So there's a lot of value to continue to understand these adult stem cells, just like why are they there and what do they do and what do they do normally in your life?

But then, as you mentioned, we could actually go from an adult cell like us, like a skin cell or blood cell, and reprogram them to an embryonic like state.

And we call those cells induced pluripotent stem cells.

And as you mentioned, they do not involve embryos.

And so it could bypass some of these ethical concerns.

One of the things that's that is fascinating to me about the work you're doing is that I believe you all have looked into the effects of COVID 19 when it comes to the brain is we focused so much on potential long term effects as far as you know, is cardiovascular concerns or, you know, as far as the effects on the lungs being compromised, that kind of thing.

And you all have have looked at the the possibility of there being some long term effects on the brain from COVID 19.

What what have you been able to determine so far?

Yeah, this is a very fascinating story.

As as you mentioned already, our research has been more focused on Alzheimer's and epilepsy.

It was it was a little bit surprising that we started working on COVID 19.

And how did that happen?

Yeah, although it's probably not entirely surprising because it's something that as a science is, you cannot not think about.

And it happened because, you know, when we when our university went into minimum operate minimal operations during the pandemic, we had many of these cells, these organoids in our incubators that have been growing for months and months.

And we certainly wanted to make sure they're used for something very, very important.

So my graduate student, Courtney McMahon at the time decided to pivot her research, which was focusing on other infectious diseases to COVID 19.

And so we were very fortunate to be able to collaborate with Ricardo Carolyn's lab at Texas Biomed and other scientists.

And we were we could just directly infect our brain organoids with the SARS-CoV-2 virus, the virus that causes COVID 19.

And so those early studies then paved the way to subsequent work that we've replicated in in mouse models that carry the human sized receptor, the entry receptor for COVID 19.

And what we've actually found in work that is currently under review at a at a public at a journal, is that that there is what we really wanted to know is women who are pregnant and who may have not had the have not been vaccinated during this period, whether or not they're their babies had any symptoms, that might be just something to watch.

This is if they became infected while they were pregnant.

That's right.

Exactly.

And so we wanted to model this in the mice.

And what we found is that the the mice that were born from the infected mothers, these are mice, infected mice do have some of the neurological symptoms as they grow up and that they are having some impairment in certain memory tests for mice.

So it's it's a little concerning.

And and so we I mean, fortunately now we all have the vaccine and and we're all getting our boosters, our people being tested in any way, people who've gone through COVID and are is there any testing being done in the medical community to see how people are suffering any ill brain effects from from having COVID?

I think that we know a lot more about why people are having some of these symptoms, especially these neurological symptoms related to COVID.

We call them long COVID.

And and I think that there is a lot more testing that's going on and recent work also suggesting that the work that we are seeing in animal models, there might be hints of this also in the human population.

So so some of those chil the children that are that are that might be susceptible, it's again, something that we want to watch out for and pay more attention to them know.

I know the Brain Health consortium has received funding from various sources, but the state of Texas hasn't hasn't gotten behind the work you're doing or I guess brain research in general.

Is that fair to say at this point?

but I'm optimistic that that that Texas will be very interested in this.

There is as you know, there's a really wonderful funding for cancer research here in Texas, and I believe there is tremendous momentum to pass a brain health bill that's similar to the cancer funding, that hopefully it'll make its way through the legislature and end up on our ballots.

Yeah, I would certainly hope so, too.

I you were talking about epilepsy is one of the the something that you are studying also.

And I think there are about 65 million people around the world suffering from it.

And there are many people who don't respond to antiseizure drugs.

What can you tell us about some of the advances that are being made in understanding epilepsy and how to treat it?

Well, definitely, it's it's a very common neurological disorder.

I know many people who personally have it, and there are there are fortunately, there are antiseizure medications, but there are patients where they are resistant to the are pharmaco resistant to some of these current available medications.

And surgery is not always an option as well.

Many of these tend to be young patients.

And so and so there are some experimental therapies like neurostimulation is very exciting right now to to try it's it's been neurostimulation is is first being used for like Parkinson's and other movement disorders.

So I think there is a there's research going on to see how that might be able to transfer over to epilepsy.

I also think that there's a lot of basic research that's happening that's very exciting and compelling and could lead the way to new therapeutic targets and strategies like, for example, these these stem cell strategies that I'm talking to you about.

And the third area, that's it's it's very early days, but there is research trying to figure out how to do cell therapy.

So one of the reasons why patients develop these epileptic seizures is a loss of a certain type of brain cell.

And so you can imagine putting those brain cells back, but you've got to figure out to do it in the right time, in the right place without causing more seizures.

We've seen such advances in artificial intelligence technology in recent years.

Does it play any role or do you see it play any role in in the work that you're doing?

We do see a role, of course, you know, artificial intelligence technologies is such an exciting area.

Like any new tool or technology, if use in an ethical manner can help science go forward.

And at the same time, AI technology itself is also advancing to be more realistic based on our knowledge of the brain.

So it's interesting you mentioned that because the brain and I go hand in hand, we don't know as much at this point for both systems, but there is a lot of research, including the research that scientists at UTSA are doing to try to integrate the two systems and look at that interface.

We've just got a little bit of time left, but I wanted to ask you, given all that you know about the brain and all the work you've done to it, are there any sort of just general like practices or that you recommend you recommend to people as far as preservation of brain health?

I think we all I get asked this question a lot and and of course, you know, we all think there could be like a magic pill that scientists should figure out what to do.

But a lot of it is like very basic things like healthy hell have a healthy life.

Diet and exercise and sleep And sleep is probably the biggest thing right now that we are realizing and and know that it's so important for our brain.

Dr. Hsieh, thank you so much for being in Texas Talk.

I really appreciate it.

Thank you very much for having me.

That's all for this edition of Texas Talk.

Thanks for watching.

We'd love to hear from you.

If you have any questions or thoughts you want to share, please email us at texastalk@klrn.org.

We'll be back next month with a new guest.

Until then, take care.