Genes, Nutrition, and Personalized Health: Exploring Metabolic Research

00:08 Dr. Kate Townsend Creasy

I think that's really exciting because a lot of times people have ideas about what we call “fad diets” in the general public, but those fad diets might actually be really helpful to certain people. So it's just finding the right interventions for the right people to be the most efficacious.

00:33 Nicole Chung

Hello everyone, this is Nicole. You're listening to Ever Thought About…?, created by undergraduate students at the University of Pennsylvania. We hope to bring you exciting episodes about the diverse research undertaken around campus. Sit down with us as we chat with Penn professors about the work they've dedicated their lives to. In this episode, we explore research on nutrition science with Dr. Kate Townsend Creasy. Dr. Creasy is an Assistant Professor of Nutrition Science in the School of Nursing at Penn. She received her PhD in Nutritional Sciences from the University of Kentucky, followed by a postdoctoral fellowship at the University of California, San Francisco, with additional training with Dr. Dan Rader in the Department of Genetics at Penn. Her research focuses on the intersection of human genetics and nutrient metabolism in the cardiometabolic diseases. She has over 11 years of experience investigating how changes in liver lipid metabolism contribute to complex diseases, with the goal of improving diagnostics and therapeutic strategies. The Creasy lab uses cutting-edge techniques, including multi-omics and single-cell analysis, to understand why some people are more likely to develop metabolic diseases. Dr. Creasy is especially passionate about using this knowledge to design personalized nutrition strategies that improve health for everyone, especially those from underserved communities. As a first-generation college graduate from a rural background, she's committed to making science more accessible and relevant to students from all walks of life. Just to get started, how did you become interested in the field of nutrition science, and what drew you specifically to focus on genetic and regulatory mechanisms of liver lipid metabolism?

02:27 Dr. C

Thank you for that question, and thank you for having me. I first got interested in this because I was just observing people around me, really, and I saw that it was a huge problem where a lot of people had really unhealthy lifestyles and had increased risk of diseases, and you could see the toll that takes on people. So I was really interested in understanding, was this a genetic factor? And then what can we do about it to try to help prevent really advanced disease. So I think that the connection of genetics with nutrition is a good focal point to try to solve that problem.

03:01 Nicole

That's really inspiring, dedicating your career to research. So, can you walk us through a typical day in your life as a researcher?

03:09 Dr. C

Oh my goodness, yeah. So we have a lot of different and very exciting projects going on. So depending on what is active in the lab in the moment, it can look very different. For one project that I'm really excited about, we are getting human tissues from people who are undergoing bariatric surgery. So if a patient is scheduled that day, we have to coordinate with the clinical teams and the surgical teams to be able to gather the liver biopsies and adipose samples from these patients. They get to come back to the lab and we have to process them so we don't have any degradation of the tissues. And then we start to prepare them to do single-cell sequencing. And that's a process where we can break up all of the tissue into individual cells. Because when you start to develop a disease, not every cell will be diseased in the tissue. So now we can see which are healthy cells versus diseased cells and try to understand the progression of disease and how it affects an entire tissue. So other projects that we do, we use a lot of mouse models of metabolic diseases, and that way we can create genetically modified mouse lines and try to understand how those genes are affecting their metabolism and then how that can contribute or prevent disease. So if we have mice studies going on, that a lot of times involves weighing the mice, collecting their blood, feeding them different diets to see how that affects their disease progression. And then a lot of times it's just analyzing data, writing it up, trying to get grants and manuscripts, which is the ultimate goal of all of the work that we're doing.

04:42 Nicole

Fantastic. I really connected with the mouse models because I used to work with mice and rats to study like the effects of GLP-1.

04:49 Dr. C

Oh, interesting.

04:50 Nicole

So a lot of animal handling. Your lab uses cutting-edge techniques to characterize changes in liver disease patients. So can you explain more about the techniques that you use and how these methods contribute to the development of precision nutrition care?

05:07 Dr. C

For sure, that's definitely an area where we're really excited because we're able to, again, take human samples, but also look specifically at independent genes using our mouse models. And with both human and mouse samples, we can look at the genomic component of it as well as metabolomics. So again, we're doing the single-cell sequencing from human tissues, which will tell us on an individual level how cells are changing their gene expression, their transcriptomes, during the development of a disease, and then that will give us more insights into how we can develop better biomarkers and detect it earlier and get better treatment options for patients, hopefully, down the line. And then additionally, we are doing large-scale omics and multi-omics studies. Where we're looking, again, starting from the genomics of a patient, looking at the single cell transcriptomics, and then even into their blood samples, looking at metabolomics. And again, trying to tie it all together to just have a better picture of the entire disease process. And that gives us a lot more information that we can analyze bioinformatically to detect biomarkers at earlier stages, hopefully at some point have better therapeutics, and then also look at the interaction between the gene and environment where we can intervene with precision nutrition. So by understanding the metabolic processes, we can discover if a person is a better metabolizer of, for example, carbohydrates versus fats. And if that's the case, based on their genetic profiles and their risk for metabolic disease, we can recommend a precision nutrition intervention there where they try to avoid high fat intake. Or if the opposite is true, a low-carb diet might be really optimal for someone. I think that's really exciting because a lot of times people have ideas about what we call “fad diets” in the general public. But those fad diets might actually be really helpful to certain people. So it's just finding the right interventions for the right people to be the most efficacious.

07:06 Nicole

Listening to some of the techniques that you use, it seems like your research is very interdisciplinary, so there's like a combination of nutrition and genetics. So I understand that you collaborate with multiple teams to conduct translational metabolic disease research. So can you talk about how these different disciplines intertwine with nutrition?

07:26 Dr. C

Absolutely, and I think that that's really the future of multifaceted research because we develop expertise in a certain area, but if we really want to look at a holistic view of disease and also treatments, we need expertise from different areas. And so that's where collaborating with people from these different fields is really beneficial. So absolutely, I love to collaborate with bioinformaticians and biostatisticians. They are absolutely integral to creating the data outputs that we get from these massive data sets. And then having people who are experts in looking at genomic studies, as well as people who are experts in the actual biochemical assays to help interpret the results that we're generating. All of this is really important to have an accurate and also just really well-designed and thorough study. All of these metabolic diseases are very complex, so it's very difficult for any one person to be an expert in all areas. It's really much more beneficial to the entire scientific community to have a very multidisciplinary team that works well together.

08:27 Nicole

Interesting. And now I'd like us to delve deeper into some of your studies. So in your 2023 cohort study on the “Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality”, it involved more than 1.7 million people. What were the challenges when conducting such a large-scale study?

08:49 Dr. C

You can imagine there are a lot of challenges. The larger the study, the more diverse the different parameters are of all of the participants in a study. So it makes it really hard to control for a lot of factors. People have a lot of different lifestyles, a lot of different genetics, a lot of different factors that could be influencing the results that we're trying to understand. So again, having a really good bioinformatics team that can help us develop appropriate models of all of the data is really necessary for that. It goes through several levels of data refinement to make sure that we have the best quality data possible, and then also to make sure that we're accounting for the correct controls and analyzing the data correctly. But for sure, it makes it much more interesting and I think a little bit more powerful to have such a large data set, and you can find more interesting associations to study further, but there are definitely challenges to handling that data as well.

09:42 Nicole

So, moving forward, where do you see your research heading in the next five years or 10 years? 

09:48 Dr. C

I think that right now is a really opportune time for precision nutrition. Nutrition especially is something that most people are aware of. People have to eat every single day. So it's a little bit of a challenge to really set standards for the science of nutrition-related research, because most people feel like they're familiar with it, and then that leaves room for a lot of false information to be circulated. So as our scientific methods improve, and hopefully we can improve our dissemination of our data, our work, as well as everybody else who's working on similar projects, we can start to get better information out to the public and better reception about that. So I think with higher throughput multi-omics data and, again, better communication about our research to the public through social media avenues, that's really going to allow us to reach more people, inform more people, and then hopefully just really allow this field to grow.

10:49 Nicole

Following up on that, what do you think are the major misperceptions of nutrition science?

10:55 Dr. C

Oh my goodness, I think there's so many. So, everyone has their own experience with food and a way of eating. So people feel like they know the best thing. And that might not be founded in any actual fact, that might just be something that works for an individual person. So that's not wrong for that person to then want to eat that way, but that doesn't mean that that's the correct way and advice should be based on that one individual experience to give to many other people. So I think especially right now with using GLP-1s actually for weight loss where it is very beneficial for people, but you also have to make sure that you're accounting for micronutrient intake and making sure that you're not setting yourself up for potential other metabolic conditions down the line by using these for faster weight loss, but it might actually be increasing your risk of other diseases because you have lower micronutrient intake levels. So that's been a problem, I think, that's popped up more recently because you're selling GLP-1s at even sort of boutique spas now. You don't need prescriptions for them. They're not being monitored by medical professionals. So that's a big issue. But really, I think you can pick any, what's known, again, as a “fad diet” and people will be ardent proponents of it or extremely opposed to it, just depending on who you talk to. So we need better research that actually looks at it and the specific people who might be responding to a diet in a way that is beneficial for their health.

12:19 Nicole

Absolutely. How would you recommend a student to get into nutrition research and what would be a good starting point for them?

12:26 Dr. C

Especially at Penn, I think that this is so important. We have a lot of opportunities. So there is a group here called PenNSAM, which is the Penn Nutrition Science and Medicine Group. If you go to that website, they have a lot of resources of the members of that research group who you can contact and see if they have openings in their lab for research opportunities. CURF and PURM programs are a great place to connect undergraduate researchers with the PIs who have openings and projects available. We have an institute on diabetes and obesity that also has a lot of labs that are always welcoming for undergraduate researchers.

13:08 Nicole

Can you talk a little bit about your mentorship with undergraduate students and what roles they have played in your research projects?

13:14 Dr. C

Yeah, they've been absolutely critical to advancing a lot of our projects. So my first year as a faculty member at Penn, I was able to get a couple of students through PURM. And a couple of them have stayed with me for the last few years to further develop their projects and their skills and are using work that they've done to actually write manuscripts so that they are in better positions as they’re applying for med school soon. We've had a couple of undergrads who have worked in the lab through the Institute for Translational Medicine here at Penn. So I rely heavily on undergraduates. I think that they're incredibly valuable to help move projects forward. And it's a mutually beneficial experience, hopefully. I get a lot of really good productivity out of undergraduates, and hopefully they learn a lot of lab skills. And I think another important point for undergraduates is to try whatever is interesting to you. And you might then find out that you don't actually like that type of work. But it's important to know that too. That's still a learning experience. So I think finding something that is interesting and then seeing if it still continues to be beneficial to you is an important component of having an undergraduate research experience.

14:25 Nicole

This has been really informative and helpful. Thank you so much for your time, Dr. Creasy.

14:29 Dr. C

Thank you for having me.