Episode 76: Leigh Nicholson, Ph.D., Researcher and Ambassador

Episode 76: Leigh Nicholson, Ph.D., Researcher and Ambassador

Karie Dozer [00:00:04] I'm Karie Dozer and this is TGen talks. In addition to the work they do in the lab, many TGen researchers are ambassadors of sorts, scientists who enjoy getting out of the lab and into classrooms and science fairs and anywhere that their love of science can be shared and appreciated. On this podcast, you'll meet Dr. Lee Nicholson, whose research utilizes organoids and cell models to learn more about neurological diseases from some of the most common to some of the rarest, and why she believes in the importance of scientific literacy and sharing her passion with the next generation of researchers and the community at large. And this episode of TGen Talks, once again, as we do, often focuses on the brain. Dr. Lee Nicholson is my guest today. Thanks for joining me.

Dr. Leigh Nicholson [00:00:51] You're welcome. Lovely to be.

Karie Dozer [00:00:52] Here. Tell me a little bit about what you do here at TGen in day-to-day basis.

Dr. Leigh Nicholson [00:00:56] Day to day basis. Okay. So, I came to teach in probably just over two years ago from Sydney, Australia, and I came to teach in as a post-doctoral scientist and I am now a research assistant professor and my day to day here is probably 3,040% wet lab work. And then the rest, a lot of writing and talking and sort of some training and community involvement and sort of just contributing to, you know, teach in and City of Hopes, goals of collaboration and those sorts of different projects I work in. So, Matt Huntsman's lab, which is neuro genomics focused, so a lot of the wet lab projects that I work on are for me specifically, usually looking at developing cell models to study different brain diseases and using those models and optimizing them to sort of come up with different ways that some of those diseases might be able to be treated. 

Karie Dozer [00:01:58] What's a cell model?

Dr. Leigh Nicholson [00:01:59] A cell model for me is using. So it's an in vitro model. So it means that I don't work with patients or it's not sort of, you know, clinical focused in that sense, but it's using different kinds of cells to mimic a disease in the lab that I can then study and translate back to either what that disease looks like in a person or how that might be able to be treated by different, you know, like drug treatments or targets or things like that.

Karie Dozer [00:02:30] Cell models are probably used in research of the brain more than other areas. Right? Because it's hard to access brain tissue right now. People are not willing to give it is.

Dr. Leigh Nicholson [00:02:39] Yes. So I've worked in like a lot of different scientific areas. My PhD was actually in reproduction in cancer, and then my first post-doc was in immunology. But because my focus is on using these different models to study different diseases, it is actually sort of easier than it seems to use that in different kind of scientific areas. But neuroscience, absolutely, it is very hard to a access the brain and like a person and sort of look at some of the molecular biology underlying different diseases. But then also obviously animal models are used and that's quite different. 

Karie Dozer [00:03:16] So your diverse path, obviously it all focuses around genomics. Why are you currently focused on neuro genomics? What is so exciting for you about that?

Dr. Leigh Nicholson [00:03:27] Field? It's a great question. It's something that I enjoy, I think a little bit more than some of the other areas that I've worked in, not because I think that it's, you know, necessarily more like forefront or important or anything like that. But personally, for myself, the combination of molecular biology, looking at cells, looking at what they do with the aspects of neuroscience inherent in like thought and, you know, how people sort of age and how issues in their brain affects their life and people around them. That's a sort of very unique thing to neuro genomics, which I enjoy.

Karie Dozer [00:04:04] What are some of the main focus of your research?

Dr. Leigh Nicholson [00:04:06] So a big, big part of what I do is looking at aging and Alzheimer's disease. I also look at some rare childhood neurodevelopmental diseases or some where we're actually not sure what that what that disorder is. And it's sort of part of, you know, identifying what if, if there's like a genetic mutation that might be contributing to some kind of pathology in these in these children. I also do some work on a disease called RC. And yes, it's a very rare neurodevelopmental disorder that is usually identified in children. So I think there's something like or only 220 diagnosed cases and as is the case with a lot of rare developmental disorders, not a lot is known about it. We know that there is a gene and we know that there are certain mutations in this gene that can cause or. Yes, but not a lot is known about the molecular biology underlying it and sort of how that these different mutations can cause developmental delay and these different symptoms seen in these children.

Karie Dozer [00:05:17] The numbers of children with Oka Chung is small. How does that contribute to the difficulty in trying to find answers?

Dr. Leigh Nicholson [00:05:24] Yeah, absolutely. So there are a lot of issues. One, I mean, one is that when there is a small cohort of people who have a disorder, it's very difficult to diagnose. And that obviously poses a lot of problems for people who are trying to get answers specifically for the children. So it's a very sort of sensitive area, but it's also it's difficult to sort of find information about and diagnose. And then it's also difficult to understand the molecular biology underlying it because it's not a big cohort. So you can't sort of study it in the same way that you might study a disease that has a larger group of diagnosed people. Obviously also diseases that involve children are difficult to study just based on, you know, like how development works and sort of the different kinds of studies that you can do with patients. 

Karie Dozer [00:06:15] Do parents of children with Oka Chang or what they believe might be Oka Chang How do they find T gen? How do they participate in research? How is it that you find them, interact with them and try to help them? 

Dr. Leigh Nicholson [00:06:27] So the work that I am currently doing on R, C and D. S is supported by the CSA and K 21 Foundation, and this is a foundation that provides resources and support both for families and patients that have this disorder and also for researchers who are researching this and to sort of promote and support that that area. The work that I'm doing at the moment is a sort of it's a short project supported by the foundation where we are going to be looking at using different cell models and in vitro models in the lab, trying to understand a little bit more about that molecular biology underlying the disease.

Karie Dozer [00:07:07] With so little information about a disorder like this, is it sometimes hard to figure out the questions you even want to answer?

Dr. Leigh Nicholson [00:07:15] Yeah, it is. No, absolutely. I think this is probably in my wheelhouse of the, you know, disease models. But because we know these mutations that cause this disease and we know the symptoms that are seen, the question that I am starting with because so little is known about it, is a very broad I'm growing cells and using different models and experiments to look at how those mutations might affect normal growth of different kinds of brain cells. 

Karie Dozer [00:07:50] Obviously everybody knows about Alzheimer's or at least know somebody with it. Not everybody knows somebody with Oka Chung syndrome. What are other questions that you want to answer, areas that you want to jump into?

Dr. Leigh Nicholson [00:08:01] So one of the one of the areas that I'm also working on is so I do different cell models, some that involve the use of organoids, which are these 3D cell models that we can use to study diseases because we can grow different cells like, you know, neurons or astrocytes, which are important cells in the brain from stem cells. And I have also been looking at in regards to Alzheimer's disease, the vascular vasculature of Alzheimer's disease using blood vessel Organoids, which is a different kind of organoids. So we have brain organoids, we have blood vessel Organoids and they sort of do a pretty good job of mimicking some areas of the body that we want to have a look at. If there's a an effect that a genetic mutation might be having on it. So I think at the moment, probably my focus is partly split between Alzheimer's and or C and D s, but a lot of the work that I do is because it's using and optimizing different cell models. It can be easily used in some of the other diseases that other people in the lab might be working on.

Karie Dozer [00:09:20] Will it allow you to change direction again? Will your diverse path take you someplace else, or will you stick with that until half the time?

Dr. Leigh Nicholson [00:09:29] Yeah, I'm very happy to working on the things that I'm focusing on at the moment. There's a lot of room for different kinds of projects in the Huntsman lab, even if it is just sort of looking at different kinds of neurodevelopmental diseases. It doesn't necessarily have to be the sort of, you know, like Alzheimer's or C and D has that. I do work on. It can it can be something that we might see associated with another kind of mutation. And that's sort of the beauty of what I enjoy about cell models. 

Karie Dozer [00:10:01] I've been told that you also enjoy getting out of the lab. And talking to kids who might want to jump into science on mentoring kids. Why that? It seems like such an opposite of what you do every day in the lab.

Dr. Leigh Nicholson [00:10:13] Yeah, I, I mean, I think that it is probably partially two things. One is that I think that community involvement and teaching or even just speaking about science at different levels of understanding with different kinds of audiences, whether it's quite young kids or high school or just general members of the community. I think scientific literacy is very important. I think that understanding what science research looks like is also very important. But then the other part is that I just generally enjoy speaking to different people about different areas of science. I also enjoy teaching. I did a lot of teaching and lecturing during my Ph.D. and my first postdoc, and it's just something that I sort of also enjoy talking about. 

Karie Dozer [00:11:02] Was there someone who mentored you or came to a class when you were in the sixth grade and talked about science that got you going?

Dr. Leigh Nicholson [00:11:09] Yeah, definitely. Definitely. One person comes to mind, too. Her name is Alice and she's a professor of chemistry, actually. And she's probably maybe like ten years, like, ahead of my career.

Karie Dozer [00:11:22] That's old enough. Yeah.

Dr. Leigh Nicholson [00:11:23] And it was. It turned into more of like a I would just come to her to ask random questions about like, how can I get into this area or does this seem like a good idea? And then it sort of, I think, snowballed into a little bit more of asking some more formal advice, you know, giving like reference letters, that kind of thing. I hope that she also gets a sort of similar amount of joy out of our friendship as I do. 

Karie Dozer [00:11:49] I hope so.

Dr. Leigh Nicholson [00:11:49] Knows my wedding.

Karie Dozer [00:11:50] So I think we're in then. Yeah. What is most rewarding about the work that you do and about being among so many other like-minded people at T Gen?

Dr. Leigh Nicholson [00:12:01] I think it's rewarding on both like global and local sense. The global sense is that I enjoy contributing to like it sounds corny, but I guess just science in general. I enjoy sort of helping doing work that I see as having an implication for someone who might be, you know, struggling with like some kind of a disorder or a disease or even if it's just contributing to understanding. Because knowing something about something can help people feel better. I think the local sense is that I also just genuinely get a lot of joy out of the day-to-day work that I do. I enjoy working in the lab. I enjoy working with a lot of different people. I enjoy writing and speaking to people. So it's sort of a great mix of all of those things. 

Karie Dozer [00:12:50] Okay. As we wrap up, is there anything that I've missed? Anything you wanted me to ask that I didn't.

Dr. Leigh Nicholson [00:12:55] Know I have? Yeah. No, I enjoyed speaking about the work that I do. I love hearing about the work that other people do, even in, like, you know, the same building where we might have a little bit of crossover. And then it's something that I find out about what they've been working on that's really genuinely interesting. And yeah.

Karie Dozer [00:13:14] There's a lot of interesting doors you connect. 

Dr. Leigh Nicholson [00:13:17] Yeah, that is.

Karie Dozer [00:13:18] All right. Dr. Leigh Nicholson, thanks for your time today.

Dr. Leigh Nicholson [00:13:20] Thank you so much.

Karie Dozer [00:13:22] For more on TGen’s research, go to TGen dot org slash news. The Translational Genomics Research Institute, part of City of Hope, is an Arizona based nonprofit medical research institution dedicated to conducting groundbreaking research with life changing results. You can find more of these podcasts at TGen dot org slash TGen Talks, Apple and Spotify and most podcast platforms. For TGen Talks, I’m Karie Dozer.