See one, do one, teach one: The importance of paying it forward as scientists

With metabolic processes being a complicated aspect of biology, it takes specially trained scientists with a respect for the multidisciplinary approaches to tackle the science and the innovation related to this area. Today, we are joined by Dr. Ashley Snider, an Associate Professor of Nutritional Science and Cancer Biology at the University of Arizona. Having received her Ph.D. in Pharmacology and Toxicology, Dr. Snider aims to understand more about fatty acids and their effect on inflammation and gastrointestinal diseases including colorectal cancer. She is a member of the BIO5 Institute and most recently was selected a 2022 Women of Impact recipient for UArizona Research, Innovation & Impact based on her commitment to the university’s mission and values, an application of skills toward discovery and innovation, the enrichment of our community, and the empowerment of others to ensure lasting change.

I saw that you got your bachelor's degree in marine biology, is that correct? 

Yes, I did my undergrad in marine biology at the University of North Carolina at Wilmington. I fully intended to go to grad school in marine bio medicine, and through a series of random events, ended up here at the University of Arizona studying fatty assets and gastrointestinal diseases. 

Do you want to rip on those random things that led you here, and talk about where that intersection ended up occurring and took you on this new path?

Sure, I took a couple of opportunities in undergrad to do some research. I was really interested in population genetics, echolocation, and broad interests; maybe some basic research, and I applied to the Medical University of South Carolina for their marine biomedicine program. I got in, and the program was a little longer than I anticipated, and the mentor relationship that I thought was going to be there wasn't. I rotated through a couple of other labs, and I did a gene therapy lab, a stem cell lab, and then a cell signaling lab looking at specific lipids in ovarian cancer. I was really struggling to choose a lab and choose a path for the rest of my career, and I got maybe the best advice I've ever gotten in my career: choose a mentor that you want to be like. I ended up in the laboratory of Kate Meyer, and we studied a lipid called lysophosphatidic acid, and how it influences growth in ovarian cancer. The lipid signaling carried on throughout my postdoc and junior faculty, and that was actually what led me to be recruited here to the University of Arizona. The more I talk and share that story with other people, it's nice to hear that there are a few who had this direct track, but not many. 

I love that. I know we're fast forwarding through a lot to today, but I'm really fascinated by the space you're working in now with stomach issues, this whole area of inflammation, and how this metabolic process really impacts every function of our body and in our life. Talk a little bit about your work today, what you're working on, and what that means to somebody that is searching for answers.

Right, so I'm part of the Precision Nutrition and Wellness Initiative, and that's really what we're trying to get at; figuring out how to make foods work to make us work better. My lab is really interested in the dietary fats that you eat, and how they feed into our lipids of interest, which are Sphingolipids. Most everyone, whether they realize it or not, knows about Sphingolipids. 

Ceramides are in a lot of skin care products, and that is one of the hubs of Sphingolipid metabolism. We're really interested in how your diet feeds into that pathway, and then what that does to gut health. If we can tweak the pathway by turning enzymes on or off, can we shuttle more towards an anti inflammatory phenotype? If we have an over-expression of some enzymes in that pathway and instances of inflammatory bowel disease or colorectal cancer, does that increase inflammation and increase disease? That's really what my career has been focused on as an independent scientist, is those enzymes and their roles in inflammatory bowel disease and colorectal cancer. Coming here to the University of Arizona, we've really jumped into the nutrition aspect of that, and how what we eat drives the generation of lipids in our bodies and what that does.

It is really so important today because someone can eat healthy, but it’s so much more than that; it's about the ingredients and just how they interact with your body. It makes a huge difference, but people don't understand or know that.

It really does, and that's actually how we got into this field. I started, 15-16 years ago, looking at these enzymes and their role in inflammatory bowel disease. I have a family member with Chron’s, and that's really what gave me the personal impetus to start studying this. We're getting there, we're better than we have been, but we're not at a place yet where we can say, “eat this, don't eat that.” Some things we can, but what we're really hoping to do is be able to say to people, who are suffering with these diseases, that we know these dietary facts do this, and maybe in conjunction with this and medicine, we can prescribe foods as medicine and as an adjunct or an additive to their current therapies to maybe increase their duration of remission and improve their quality of life.

How do you think we can make conversations about nutrition, about the things we eat, to be equally important in a conversation about solutions and treatments? People think that the band-aid stuff is gonna help, and sometimes it does a little bit, but that's not the solution. How do we start making people that aren't necessarily around science and scientists have that as part of the mainstream conversation along with medications?

That's a really good question, and I think we're starting to have that conversation, but in more of a medical or a science environment. We, as the field, are looking more at precision nutrition in diseases like inflammatory bowel disease, and specific cases of precision medicine for cancer patients. I think as a whole, we're getting there with nutrition. We just have to find a better way to disseminate information in a readily available package for the general population to understand, and make that more widespread and more available rather than in just those   scientific or medical instances.

Right, I'm sure it's added complications with segments of the population that just don't have the same access and knowledge, much less to healthy foods, and a way to understand how it impacts them individually. Your initiative is focused on that piece as well as how do we not just put it out there, but how do we make this kind of information and these tools accessible to populations that aren't as easy to reach or influence?

Exactly, and then on top of that you have gene diet interactions, and that's a whole big part of the precision nutrition and wellness aspect. We don't study that in my lab, but we study that in the collective space that we share here in BIO5. That's another aspect where it's the precision point of this, and how can we make this individualized but accessible to all?

Let's go back to this idea of mentorship that really changed your trajectory completely. It led you to this other path that you now become passionate and then accomplished in. Talk about how that concept of paying it forward in the areas that are most meaningful for you works in your lab and with you today.

I mentioned my PhD Mentor, who taught me how to be a strong, independent scientist because that's who she was. I started with her at the Medical University of South Carolina, and moved with her to Washington State to finish my PhD. When it came the opportunity for me to move places and do a postdoc, I ended up in the laboratory of Lina Obied, a very influential woman physician and scientist, who taught me how to be who I am today: how to ask the right questions, how to write grants, and how to mentor students. I really was part of a large collaborative group where we had the opportunity to mentor undergraduate and graduate students and each other, and realize that colleagues, friends, mentors, and mentees can always be the same people. I really try to use that mentorship that I received as a guidance for how I work with other people in my lab, within our unit, and within our school. 

I have several students in my lab. We meet at least once a week as a group, and then I meet individually with everyone every other week, at least. Usually, we'll run around the lab at 4:30pm or 5:00pm and see what everyone did for the day. Do they have any questions or want to sit down, look at some data, and answer questions? That comes from the mentors that came around at 4:30pm or 5:00pm at the end of the day. I try to be present for my students, and I think that is a really important aspect. Sometimes I'm more present than they want, I'm in the lab teaching them how to do things which I think they enjoy. I joke, but I just provide them with the framework, the knowledge, and the resources that they need to become successful. I've had the opportunity to work with a couple of different programs here at the University. One of my favorites is the Women in Science and Engineering; it's the Wise program, and I really enjoy mentoring young women in science. We're becoming more in-the-room instead of the minority. It's really stark as a junior investigator when you're one of three women in the room. I never felt different or less than, it's just nice to see representation and provide that for students, technicians, and people in the lab. I really try to be present and answer what they need and provide what they need. That's the way I was mentored, and I hope it works.

I try to encourage students to just try it, whether it's research in my lab or an internship or something, just try it. That's also how I figured out that field research probably wasn't going to be my favorite thing, and it really led me more towards the molecular focus, doing population genetics in a lab. Just try it, see if you like it. Do it again, and if you don't, no harm no foul. 

‘If you don't try, you really don't know what it is.’ Thank you for that. Dr. Barton, who's the director of BIO5, stresses not talking about research and innovation separately from our training and education mission. It is intertwined. We are training next generation scientists because they're working on science today, and they are further in the field and keeping our senior people on their toes. The two don't exist in academia without each other, and I think that's a newer way to approach it, but it's true.

I have that conversation with the students in my lab all the time, that this is a reciprocal arrangement. That you're here doing science and learning new things, and then we get together, and we think about different ways we can take it. By the time you're done, you're actually going to be the one driving most of it. It’s see one, do one, teach one; or the student becomes the master. That's the way I like to see things go, and so that's what we aim for.

Yeah, that's great. Do you teach too?

I do. I guest lecture when asked, typically, so I can get access to students, and I really enjoy face to face instruction. I hadn't had to teach very much before I came to the University of Arizona, and the first two years were COVID, so online teaching was not my strongest suit. I probably have developed better skills since then, but being in the classroom is a lot of fun. I teach a journal club course every Spring, it’s called “Emerging Topics In Precision Nutrition and Wellness,” and I poll the students the first week of class to get a feel for what they want to learn about. We have some key things that we're going to learn, but then we also read papers and discuss and present in an open forum format because I really want them to be reading things that they're interested in and passionate about, and that goes back to the mentorship. That was one of the first things I learned when I joined Lina's lab as a postdoc. She said, “Okay, find things that you're passionate about because if you're passionate about it, you're gonna work harder and be more fulfilled in what you do.” I also try to pass that on to my students in the classroom and in the lab. 

One thing we really like to ask about are road blocks, failures, or the slower pace of science, which some aren’t expecting. How do you integrate that into not only how you're training and mentoring people, but also in your own lab and your own work? What's your go-to process for mitigating roadblocks and challenges that come up as you're trying to achieve these research goals?

It’s funny that you say failures, because academic science is full of those. What I try to do in my own career trajectory, and then what I instill in my students, is just perseverance. I submitted many, many grants before I got my first independent investigator grant, and it really is just a process of perseverance. Listening to what other people have to say, and asking and seeking that advice; to not be afraid to ask for what you need, and then expect to receive it in some form or fashion, at least within reason. Just to persevere, and then to also plan ahead. This is important for me to sustain the growth of my lab, sustain the funding, and sustain the students.

It's also really important for the students to plan ahead. Some of our experiments are 24 weeks long, or 21 days long, and either way, that's a huge investment of time and energy into an experiment, so plan ahead and know that you have the things you need to make the end of that experiment successful. I'd let them fail, and sometimes it's really uncomfortable for all of us, but they need to fail in order to know what that feels like. One, from a personal anxiety place, because a lot of students who come into a PhD program, an Honors program, or into higher education may not know what it really feels like to fail. The first grant application you submit, you're probably gonna find out. Then, think about how we could do this differently; so we build back and see what didn't work, what did, what we could do to make it better or different, improve our methodology, or improve the way we think about it. Can we plan better? Did we just forget a step and need to make sure that that's written in our notes? Do you need some more training? I'll go to the lab and help you. Really, just persevere, plan ahead, and know we're all going to fail at some point, so just learn from it and keep going.

The ultimate lesson as you’re describing is not just the lesson in failure, but the lesson that you have a net under you when you do fail. You’re providing a net and a safe space to fail, and I love that’s how you describe it, because you have to have that safe space to do that. 

It's tough for some students, but that's also what I'm trying to build; this lab family where we fail, help each other, collaborate, work together, and support each other. One of the first things I tell students when they join my lab is, “You're going to make mistakes. I just need you to be honest about them, because if we don't know where something went wrong, we can spin our wheels for quite some time trying to figure that out.” Typically, my lab manager will come in and be like, “Oh, something this and this.” I'm like, “That was me,” which is why they don't always love it when I’m in the lab. Sometimes I make a mess, but you have to be willing to say, “oh, you know, that was me. I'm really sorry.” Or, “oh, I don't think I did that step, and maybe if I go back and try again and make sure that I wrote that down and do it again, then the next one will be successful.” You need to be willing to also accept and admit mistakes. 

I love that approach. Something that's so meaningful for us here at BIO5 is integrating this excellent science that makes a difference for people and this idea of bringing people alongside you to do that and preparing them for their future. This is just an interesting question, I always like to see what people say to this. If I had to ask you in one word, what does science mean to you? 

That’s tough. Fun. Yeah, it should be fun. You should be surrounded, and that comes also into the ‘choose a mentor that you want to be like.’ Be in a lab space where you're happy, and again, the passion will come. That all kind of feeds into it being fun, and not every day is fun, but it's fun for me when I see a student say, “I got it!” They got the one piece of data that's the last piece that goes into a manuscript, or they’ve been really struggling, or something's just not working and we can't figure out why, and then there's just a light bulb or a click. That's fun, and it's fun for them too. We are building a lab where it’s a fun environment, and I think that makes students want to be here more. They want to learn more. They want to engage and interact, so we try to keep it fun. 

I love that. What's next on the radar with your work? What’re you immediately working towards that’ll be an interesting development?

Right now, we’re really interested in the fats that are in milk and how they play a part in your digestive health, for lack of a better term. We're looking at that in models of inflammation. We're looking at that in normal, healthy controls. We're looking at how that feeds into our lipids of interest, and what those do. I think in the next five to ten years, we'll have a solid feel on how those fatty acids that are milk, olive oil, or butter feed into what we're interested in, and what that does for gut health. Can we maybe start adding more milk into our diet, or maybe we don't need as much milk as we thought we did? Don't get me wrong, it's not that simple because milk provides other things besides fat, but can we look? Then maybe, can we look at ways in which we can use the fats that are in milk, and what else? What other food sources can we add to build into that puzzle, and how can we start to protect from some of the inflammatory phenotypes that we look at? We also are looking at another related type model at potential   biomarkers and colorectal cancer. I think that work has the potential to be very powerful, and we have some great clinical data, tools, and models that others don't quite yet have access to that we're going to use to start answering some of those questions. 

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