"I always knew I wanted to cure cancer."

Melissa Fishel
3D tumor cultures are helping us see how cancerous tumors interact with their microenvironment.

A Loss-inspired Dream

Being a mother has strengthened my passion for pediatric research. I have a 9-year-old daughter and a 6-year-old son. When you’re a parent, any illness affecting children touches your heart. But my journey into the world of pediatric cancer research started long before I had children of my own.

I always knew I wanted to cure cancer because I lost my dad to cancer at a young age. As I was growing up in Zionsville, I thought I wanted to get a master’s degree and eventually work at Lilly. That’s how the dream started, but most importantly I wanted to make a difference so that another little girl did not lose her dad.

Reaching Higher

I went to the University of Dayton and majored in chemistry. I discovered I really liked applying the biology and chemistry to problems. I also discovered that somebody who takes you under their wing can make a big difference. My undergrad mentor said, “You can drive your own project, you have your own ideas – you should get a Ph.D.” I never thought I could have a Ph.D. It seemed so far off and HARD. He really pushed me to apply to programs, and he believed in me, which helped me to believe in myself.

Another push came after my college roommate, Regina Marcello, got liver cancer. She wanted to get a master’s or Ph.D. in psychology. Unfortunately, she didn’t get to pursue her dreams. Regina was treated on a pediatric unit, but cancer ultimately took her life. Her death spurred on my desire to work in cancer, and to complete a Ph.D.

One Step at a Time

Out of all the Ph.D. programs I looked at, I chose the IU School of Medicine because the faculty’s research seemed the most clinically applicable compared to other programs which focused on more basic science. I worked with Mark Kelley, Ph.D., right across the street from Riley Hospital and University Hospital, where my dad was treated. I took it one step at a time. That was how I completed my doctorate.

My post-doc research at University of Chicago focused on making chemotherapy work more effectively. That’s where I’ve built my career. Tumors have a lot of tricks up their sleeves. Cancer is smart in how it combats what we throw at it. My goal is to understand it even better to figure out how to kill it.

New Attacks on Cancer

Now, I work in the Wells Center for Pediatric Research, attached to Riley Hospital. In the lab I’m trying to model tumors better by also using cells from their microenvironment. We’re using 3D cultures so the cells grow more like tumors in a dish rather than cells stuck to plastic.

We’re also working on a study involving a protein called Stat3. It’s a transcription factor that helps cancer cells make proteins that make them grow, invade and spread. My team became interested in Stat3 after finding that it could be regulated by another protein called Ape1, which we have been studying for several years. We found that in pediatric cancers such as glioblastoma, if you inhibit both Ape1 and Stat3 at the same time, the cells are strongly affected. In other words, we can take doses of both inhibitors that don’t kill the cells by themselves, and put them together, and the cancer cells are dramatically killed following treatment.

We’re hoping that can help us use lower doses and still get positive results. We want to go after the targeted cells without hurting the healthy ones and using lower doses in kids has a huge benefit long term.

Right now I’m working with a medicinal chemist from the University of Toronto who has created a variety of new Stat3 compounds to test in mice. Once we find out if the drugs are stable in the mice, we will do tumor studies. I am excited about the potential of this work.We know that this should ultimately be able to have impact on cancer.

The Highest of Stakes

When I am in the lab, I often think of the children across the street in the Riley Cancer Center. I think about my own kids’ futures. I think about my roommate. I think about my dad. I think about my faith in God, which has also propelled me along this career path.

Knowing what’s at stake pushes me forward each day.

Melissa Fishel, Ph.D.

Assistant Research Professor Department of Pediatrics IU School of Medicine

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