Switching Gears: Metabolic Rewiring in Cancer #MetabolismMondays

The world’s a metabolic dance & early career scientists are leading the way!

Emerging perspectives in metabolism

This week, we explore the story of Dr. Luis Cedeno-Rosario, a postdoctoral researcher in the Rutter Lab at the University of Utah. Luis’s path into metabolism began with a biochemistry class—an early glimpse into how cells adapt, survive, and respond to their world. His work explores how cancer cells alter their internal wiring to support unchecked growth and resist treatment—uncovering how shifts in metabolism can give tumors a survival advantage. These insights may help identify new ways to target cancer by exploiting its metabolic dependencies. Continue reading to learn how Luis is driven by curiosity, scientific precision, and how having a supportive mentoring environment impacted his journey. Check out his thoughts on how he winds science and music together, and how he views metabolism more than just chemistry— but as a language through which disease reveals its secrets and a window into how life adapts under pressure. Give him a follow over twitter and bluesky.

What’s your first memory of the field of metabolism? Could you share your journey into studying metabolism in disease contexts like cancer and cardiac disorders?

I have always been passionate about understanding how cells adapt to different environments and challenges, with a focus on cancer cell signaling and mitochondrial metabolism. I was taking a biochemistry and cell and molecular biology class as an undergraduate student at the University of Puerto Rico – Humacao and became fascinated by how multiple pathways intersect to regulate this process and their impact on cell behavior. I also had the great opportunity to do summer research internships at UT MD Anderson Cancer Center and at Johns Hopkins University which allowed me to learn more about the cell signaling and metabolism field. This is what led me to pursue a PhD in cell signaling in Dr. Deborah Chadee’s lab at the University of Toledo and a postdoc in metabolism in Dr. Jared Rutter’s lab at the University of Utah.

Introduce us to the field of cancer metabolism – you have worked on different types of cancer cells like ovarian cancer cells and liver cancer cells – tell us about your experiences.

During my first year of graduate school, I knew that I wanted to study cell signaling but I wasn’t sure in what context. I remember listening to Dr. Chadee’s talk in the signal transduction class and I was very fascinated by the complexity of the MAP Kinase signaling pathways and their role in ovarian cancer progression. Therefore, I decided to complete my PhD under the mentoring of Dr. Chadee where I worked on the regulation of the MAP3K MLK3 by CDK1 and CDK2 and their role in controlling cell division and proliferation in ovarian cancer cells (Check out the paper here). For my postdoc in the Rutter lab, I wanted to apply what I learnt during graduate school in the context of mitochondrial metabolism and their signaling pathways that are involved in liver cancer cell proliferation and progression.

How are different cells metabolically heterogeneous within the same tumor? Why is it important to study metabolic heterogeneity in cancer occurrence/progression – in term of both the cells themselves and the microenvironment?

Cells can have different metabolic profiles depending on the metabolites they need or are available in their surroundings. That heterogeneity can also come from where these cells are localized, for example, cells that are in a more hypoxic environment will probably have other metabolic needs than cells that are in a less hypoxic or normal environment. So cells have evolved in a way that they are very smart in choosing or taking what they need to meet their metabolic demands.

Tell us about your current work on metabolic signaling in the context of Wnt/beta-catenin pathway activation in liver cancer cells. How do you link it to the mitochondrial functioning and what future questions are you most excited about?

Our lab has done extensive work in characterizing the importance of the Mitochondrial Pyruvate Carrier (MPC) and its role in proliferation and tumorigenesis. I discovered that activation of beta-catenin represses MPC expression in liver cancer cells, and that this regulation rewires mitochondrial metabolism from glucose oxidation towards fatty acid oxidation. This is particularly interesting in the context of cancers in which MPC is downregulated and fatty acid oxidation is increased. I am very excited for the future since my findings opens up new avenues to explore ways to increase MPC expression in these tumors and increase the quality of life and survival of cancer patients.

Tell us how difficult some of these experiments are – do you have to deal with midnight timepoints or require an army of undergrads/ long hours, has to use some un-conventional/creative tools to overcome experimental challenges etc.

Some of these experiments have been truly a challenge and I have definitely spent many many hours in the lab trying to solve multiple research questions and/or developing new techniques to study the regulation of MPC by beta-catenin. I mentored an amazing summer research student, Nimo Abdi, who helped me a lot in the beginning of this project. I also have excellent collaborators, inside and outside the lab, who have contributed to the development of new ideas and have given me new perspectives on this regulation. I am very grateful to have them as collaborators and truly believe that these efforts will make a great impact in the metabolism field.

Building upon your work in the context of liver cancer metabolism, what are your upcoming plans? What metabolic pathways do you aim to investigate further to understand cancer progression from a cell growth and signaling perspective?

This switch in metabolic profile from glucose towards fatty acid oxidation is very exciting. So we are definitely looking more in depth at the metabolic processes that are changing and at the proteins and enzymes behind that regulation. One of the big questions we are investigating right now is to understand what fatty acids these cells prefer to utilize and their implication in liver cancer progression.

Before this, you studied cell signaling in ovarian cancer cells. How was the transition between fields, and what do you carry over from your previous research? Could you shed some light on your results regarding how MLK3 (Mixed lineage kinase 3) regulates cell cycle of ovarian cancer cells and tell us about your cool findings?

I have always thought about metabolism as another way of cells to sense their environment and metabolites are signaling molecules. These are multiple signaling pathways that are interconnected, and this concept was very similar to what I studied during graduate school. During my PhD, I found that the MAP3K MLK3 (Mixed lineage kinase 3) becomes phosphorylated by CDK1 and CDK2 to control ovarian cancer cell cycle progression. This research was published in the Journal of Biological Chemistry (JBC) doi: 10.1016/j.jbc.2022.102263 and I would encourage everyone to read it. It is a very interesting story that shows how these phosphorylation events act as “on” and “off” switches to control ovarian cancer cell division and proliferation.

How do you think scientific paradigms in the field of cancer metabolism will evolve in the coming decades – in regard to the new upcoming tools? Are we moving toward a more nuanced understanding, or do you see potential pitfalls?

I feel like we have bright future in our metabolism community. We have seen the development of great techniques such as mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) that was developed in our lab to identify novel interactions between metabolites and proteins. This is a fast-growing field and we are opening more doors to understand the complexity of metabolic pathways in multiple contexts, including cancer, cardiac function and neurodegenerative diseases, and in development. I am very excited for our future findings and hope that I can contribute significantly and have a positive impact not only in the research field itself but also in training the next generation of scientists.

What role does curiosity play in your life, both within and outside of science? 

I believe that curiosity plays an important role in my scientific career. Understanding what is happening at the cellular level is pivotal in the development of new therapies, and that is what drives my passion for science. I want to be able to use my knowledge from cell and molecular mechanisms to develop new and better ways to treat multiple diseases or to at least increase the quality of life of the people affected by a particular disease.

What are the future research questions you are most excited to ask?

I am very excited about pursing metabolism in the context of cell biology and development. I think it is a field that is also growing very fast and I would like to contribute to it and make new discoveries.

Were there any pivotal moments that shaped your career path —and how have you found ways to build a supportive community in science?

I think that the most pivotal moment in my career path was creating a strong and supportive network of mentors within the cell metabolism and mitochondrial biology field. I have met many of these mentors in conferences and through the Burroughs Wellcome Fund Postdoctoral Diversity Enrichment Program (PDEP) that have been critical in my development as a future independent scientist. I am also very grateful to be part of the biochemistry department at the University of Utah and to receive a lot of internal support as a postdoctoral fellow.

How do you maintain a balance between your rigorous research activities and personal life? Are there hobbies or practices you find particularly rejuvenating?

Music! I have extensive training in classical music and I am actually a member of the Utah Medical Orchestra (UMO) where I play the flute and the piccolo. Music is definitely a big part of who I am.

If you hadn’t embarked on a career in biological research, what other profession might you have pursued, and why?

I would have pursued a law degree or a music degree in flute performance. In the law aspect, I like the complexity of finding new solutions to diverse problems. In the music aspect, I like how we can create art using a universal language and enjoy that art as a whole. Music can bring you different feelings and helps us express ourselves.

Last week we learnt about how viruses rewire and utilize host lipid metabolism using mosquitoes as a host model system with Wolbachia and dengue as viral players, check out the article – Lipids and Labyrinths (Cassandra Koh). Cassandra is a new PI, studying metabolic interactions of symbiosis and virus-virus host interactions. She is seeking motivated students and collaborators.

Check out the article All the world’s a metabolic dance, and how early career scientists are leading the way !!

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