Scientist Sees Metabolism Research Driving Potential for New Cancer Therapies

SPECIAL SERIES: WOMEN IN ONCOLOGY

Women faculty at Moffitt Cancer Center come from different backgrounds and cultures around the globe. Their areas of research and clinical care span the entire cancer continuum, including clinical science and trials, basic science, epidemiology, health outcomes, medical physics and more. Community involvement, mentorship and inclusion among faculty are foundational, and we celebrate the essential roles women play in making a difference at the cancer center and in society.

An Interview with Dr. Gina DeNicola

Gina DeNicola, PhD, is interim chair of the Department of Metabolism and Physiology and leader of the Metabolism Program at Moffitt Cancer Center. She received her doctorate in cell and molecular biology from the University of Pennsylvania, where she studied the regulation of NRF2 by oncogenic signaling in the laboratory of David Tuveson, MD, PhD. She did her postdoctoral work with Lewis Cantley, PhD, where she examined the regulation of cellular metabolism by NRF2. In May 2016, she established her own lab at Moffitt Cancer Center. Her lab studies how metabolic deregulation occurs during tumorigenesis and how mutations that promote the activation of the transcription factor NRF2 control this process. Her research uses a combination of genetically engineered mouse models, organoid culture systems and mass spectrometry metabolomics technologies.

What made you want to go into cancer research as a career?

It was really an intellectual motivation. When I was learning about cancer, I just thought it was a fascinating problem of how all of these really well-organized systems in the body could go so wrong. There were so many problems, so many questions to ask and to understand. There were so many different approaches to trying to fix what was going wrong in cancer and for therapeutic approaches. I really wanted to study it and understand cancer biology.

If you had to change careers completely, what would you be?

When I was first choosing my career path, I was really interested in foreign languages. I learned a lot of foreign languages as a high school student working in a restaurant with people from other countries. I was learning Spanish and Greek, all these languages, and I thought it was really fun. So I thought I could be an interpreter or translate books. But my parents encouraged me more toward science. And you know science is trying to understand the language of biology. So I don’t think I’ve moved too far away from it.

What are you working on right now that you’re most excited about?

My lab studies cancer metabolism. We try to understand how the metabolism of a cancer cell is different from a normal cell. Mostly, we study lung cancer but also pancreatic cancer and liver cancer. The really exciting new direction that we’re moving is trying to do as much as we can within the body. For us, that’s usually a mouse.

A lot of metabolism research over the past 15 to 20 years has been done on cells in a dish, and it’s very artificial. They get much more nutrients than they ever experience in the body. Oxygen levels aren’t physiological. So we’re moving as much as we can within the body, where we have more complex cell types than are normally found in a dish. We’re trying to study everything under physiologically relevant conditions.

I’m excited doing all of that work within the body to try to understand how metabolism is really functioning within a cancer. That is going to help us design therapies to target the growth of that cancer.

What is one of the biggest challenges in your field?

We’ve learned a lot about metabolism over the past 15 years. Although metabolism has re-emerged as an important field for cancer biology, it hasn’t really given us many new therapies. Our old chemotherapies are actually drugs that target metabolism. That’s how a lot of them work. But in the new studies, we haven’t gotten any slam dunks in the clinic, and a lot of that is because the metabolism that we thought we were we were studying, based on cells in a dish, is not really holding up. Now we are moving in vivo — into animal models and into patients as much as possible — to figure out what is the metabolism that’s happening in tumors. There’s also a lot more heterogeneity than we previously appreciated. But that’s really the challenge moving forward is finding those critical requirements that the tumors can’t just rewire their metabolism to get around. When you block one pathway, they suddenly start using a different one, and they continue growing.

Is there a cross-collaborative effort that you would like to work on in the future?

We have a wealth of patient data here. Patients are getting measurements of their blood glucose or other parameters related to metabolism. I think we can start to use that data to understand how metabolic parameters are changing during treatment and influencing response to therapies. Once we have these hypotheses, we can go back to the lab and test them and start coming up with new questions related to metabolism. That’s an area of cross-collaboration that Moffitt is uniquely positioned to do because of our unique patient resources.

Who is the person who encouraged you the most in your career, and how did they impact you?

There have been a few people who have encouraged me, but I think the first one who really made an impact was my postdoctoral advisor, Lewis Cantley. We would have these group meetings, and when I first started in the lab, I had a lot of opinions but I didn’t talk at first. He said to me pretty early on: “I want to hear your opinion.” That was really impactful on me, telling me that it is OK to speak up. He also let me work on whatever I wanted in his lab, even though it wasn’t his main interest. And he let me take everything with me when I started my lab. That generosity has really impacted me as a mentor and in my career.

How do you measure your own success?

I think a lot of times when people think about success, they are thinking about the next step and comparing themselves to other people. There’s always someone who is more “successful.” Maybe they have more papers. Maybe they have more grants. Maybe they have a higher position. But I think everyone needs to think about what success really means to them.

You could always apply for more grants. You could always publish more papers. But that doesn’t mean that you need to because maybe what you’re doing right now is enough. You don’t necessarily need to go for that next position or have a much bigger lab. It may not make you happy.

So success for me is thinking about what I really want. I’m just comparing myself to myself. If I think there are areas I want to improve on, I strive to be better in those areas. I think about my lab and the maximum size I want it to be. I don’t let it get bigger than it needs to be because I think there’s an optimal state for me and my research and my career. It’s not about the most I could possibly have, but the best situation for me.

How do you continue to grow and develop, personally and professionally?

My research is going well. We’re studying the things that I think are important. Now, as I’m developing, my goals are different. I’m focused on developing my trainees, and now they’re starting their own labs and starting to be successful. As I’m developing the next generation of scientists and my students are moving on and my postdocs are starting their own labs, some of them even here at Moffitt, I think that’s what really makes me happy. I see that as the success of my career.

Now that I’m leading our metabolism program, I’m also looking forward to recruiting faculty and supporting them as they establish their labs, get grants and publish papers. That sort of mentorship and training is really important.

What do you wish people knew about cancer prevention that’s not common knowledge?

I don’t know that people appreciate that cancer prevention goes a long way. It’s a lifetime investment to make healthy choices — to not smoke, to eat a healthy diet, to moderate alcohol consumption. All of these things have a big impact in the long run.

I’m also not sure that it’s broadly known that cancer is such a complex disease. There is no one treatment for lung cancer. There is no one treatment for pancreatic cancer. It’s all down to what stage you have and also what mutations you have within your cancer.

How do you maintain a good work/life balance?

I don’t do everything. I say no to a lot of things. I’m very cognizant about what I want to do, what’s important to me, what’s important to my goals, and I don’t take on more than I can do.

I have a responsibility to my lab. I have a responsibility to my department. If I take on more than I can do, then I do a bad job mentoring my lab, supporting them and my department. So I only take on what I can, and I do a good job at it. I keep my weekends free so that I can do other things. That makes me better at my job and makes me responsible to those whom I’ve committed to.

What support positions or unsung heroes do you most appreciate at Moffitt?

The person I want to say is an absolute hero is Wanda Williamson, senior director of basic and clinical science. She solves all the problems. Anytime I have an issue, I go to Wanda.

But I think every person at Moffitt has an important role. We don’t even recognize it until things become dysfunctional. A lot of people are operating in the background to make things work. From the people maintaining the facilities to the people keeping everything clean to the people just keeping operations moving at all levels from finance to administration. And of course the doctors and nurses. Everyone is really important to making Moffitt a well-oiled machine.