Meet a Whitehead Postdoc: Alexsia Richards

Alexsia Richards is a postdoc in Whitehead Institute Member Rudolf Jaenisch’s lab investigating how dangerous tropical viruses interact with the brain. We sat down with Richards to learn more about her and her experiences in and out of the lab.

What are you investigating?

In Rudolf’s lab we use human stem cells to produce various brain cells, brain organoids, and cells that comprise the blood brain barrier. Then we study the effects of neurotropic viruses including Japanese encephalitis virus, Zika virus, and dengue virus on the brain. Our goal is to understand how these viruses interact with the brain. I think it’s very exciting that, because of stem cell technology, for the first time we can study these viruses in the actual human cells that they infect. That hasn't been available, because you can't really get primary brain cells from humans (humans need them), so previously we had to use animal cells, which are not a great system for modeling human infections. Being able to study these things in the right cell types means we can learn things we couldn't before.

What are you working on specifically?

I have two main projects. Using stem cells, we can make human brain organoids, which are mini brain-like organs grown in the lab, but microglia, which are the immune cells of the brain, don’t innately develop in these organoids. So, the first project is to optimize delivery of the microglia to the organoid after we make it. Once this is complete we will investigate how these microglia respond to infection once we then add viruses to the organoid. Are the microglia antiviral—are they protective—or are they helping to promote infection? No one really understands the role of those immune cells when a virus gets into your brain. 

The second main project is focusing on the blood brain barrier that restricts viruses and other things in the blood from getting into the brain. Step one is can we make all of the cell types we need for the blood brain barrier from stem cells and get them to behave well together? One of the more recent types of stem-cell-derived cell we've been able to make are brain microvascular endothelial cells, the main cells that make up this barrier. Now we can set up a fake blood brain interface so the endothelial cells form a layer, and add brain cells to the other side. Step two is to test and see what viruses do when they hit that interface. The viruses I study are in your blood after you get bit by an infected mosquito, so likely they are interacting with the blood brain barrier somehow. Clearly, it's protecting us, because we don't all get super sick when we get these viruses, but we don't know how or why. What makes some viruses able to get through when others don't? We’re working on assembling a system to investigate that question.

What did you want to be as a kid?

A ballerina, but I turned out to be horribly uncoordinated. I took dance lessons when I was very little and I couldn't make it through intro level. After that, I think I wanted to be a veterinarian, and then later on I thought premed or pre-pharmacy, but I didn’t want to work with patients or customers that much. I had taken a lot of chemistry, and I thought, what can I do with all of this science? I stumbled into the idea of getting a PhD. Towards the end of college, I had a couple of really good science professors, and they made it fun. I think people tend to view science as being really hard, and it's important to have good professors who say, "This is fun. Anybody can do this." That convinced me: yeah, I can do this.

How did you end up at Whitehead Institute?

The overarching theme of my career has been how viruses interact with cells once they are inside them. I did my PhD in Wisconsin on polio virus, and then I wanted to move to a virus that currently makes people sick, because most of us are vaccinated against polio, so I switched fields to the herpes viruses, which for the most part just give you cold sores but can also cause encephalitis. I started to work on how these viruses interact with neurons and what they do when they are inside neurons. That was my short, first postdoc. We were studying these things in mouse neurons, chicken neurons, and I thought, there's got to be a better system for studying these. Everything we're learning, we have to add the caveat of it's in animal cells, so maybe none of this happens in human cells. My lab had worked a little with labs that did stem cells, and I started reading more about them, and looking up people that did stem cell work. At the time Rudolf had just published a review where he talked about using stem-cell-derived neurons and astrocytes to study viral infection, and he had recently applied for a grant with a virus lab. So, when I emailed him about doing a postdoc he said, “Hang on, let me make sure we got this grant,” and they did, so it was a good fit. They were looking for a virologist, and I was looking to learn stem cells, so we clicked.

What's the biggest disaster you've ever had in the lab?

I was using polio virus and we had to label the polio virus with radioactivity. Basically, I was spinning it in the department’s common ultracentrifuge, with the common buckets that everyone used. Nothing ended up spilling, but apparently, I hadn't gone through the right channels, and a faculty member came to me and said, "You're spinning radioactive live virus in our centrifuge?" I think once I showed that there was no radioactivity getting out, they were okay with it, but I just remember that moment of "You're doing what?" The lesson was to tell everyone you're doing it first.

What are your hobbies outside of work?

Running. I've done a few marathons. I'm uncoordinated, but I can run forward. Also, I like to do a little bit of cooking, hiking around, camping, outdoorsy things, mixed in with lots of TV. I watch way too much TV; all the major shows, like Dracula, Game of Thrones, Downton Abbey. My baseline go-to is reruns of Star Trek: The Next Generation. There are times when you get home and you're like, I can't face a new show. I just want what I know. With all the seasons online, that’s so easy to do now.

How did you get into running marathons, and what’s been your favorite?

A friend of mine in grad school had gotten into it. We talked about it a lot at work and I convinced myself that I could do it.  I've never been good at sports. I have zero hand eye coordination, but I wanted to try to do something new. I like the idea of if you're going to run, try to do the longest race you can. It became something I could do that was cheap, and there were good paths in Wisconsin. It turned out that while I was maybe not fast at it, I could do it. We ran our first marathon together. Once I did the first marathon, I was like, that's fun. Miserable, but fun.  

My favorite so far was the Chicago marathon. It's cool to wind though all the different neighborhoods of the city. My least favorite one was the Cape Cod marathon. When they tell you it's hilly, they're not lying.

Do you have any pets?

I have a lab beagle mix. He's a rescue dog. His name is McGee, like the NCIS character. We were on an NCIS binge when we got him. I think it came down to Riker or McGee, either Star Trek or NCIS, and he felt more like a McGee. It’s funny because now, knowing his personality, he’s much more of a McGee.  He tries to be tough but if there's a bush out of place he jumps back. He's cautious, just like McGee.

What's your favorite thing about your job?

It sounds cheesy, but my favorite thing is the idea that something you do could really impact health or medical care. It's a long road from A to B, but it’s a great feeling to know that what you're working on has that potential. You get to be on the ground floor. I also like that every day is different. There's always the possibility to learn something really cool, and there’s a little bit of excitement to every day.

Where do you see yourself in ten years?

I'm still into the full-on academic dream, so hopefully running a lab. I'm from the Midwest mostly, so I'd like to move back and run a lab there. I like the idea of being at a smaller school, outside of Boston, nurturing grad students. I think sometimes those schools gets under-recognized. They don't have the fancy names, but I think those places give you more flexibility in terms of building new programs, since they are not as set in their ways as far as how things should be done. I really like the idea of going somewhere like that and trying to bring their programs up.