Like gift boxes in brown paper waiting to be mailed, our DNA is contained in packaging material with unique instructions that until relatively recently remained a mysterious curiosity. A field of study called epigenetics focuses on understanding how this packaging material provides instructions that inform cell functions. Dr. Piroska Szabó, associate professor in the Institute’s Center for Epigenetics, has dedicated her life to understanding how these epigenetic factors influence the very beginning stages of human development.
VAI Voice had the opportunity to speak with Dr. Szabó and learn about her life as a scientist, her work at the Institute and what gives her hope for the future.
Where did your story begin — where did you grow up?
I grew up in Szeged, in the southern part of Hungary. Szeged is a very nice and sunny city, about the size of Grand Rapids and there are quite a few similarities between the two towns. Szeged is the region’s center for culture, education and science, just as Grand Rapids is to Western Michigan. The river Tisza runs through Szeged, and I remember it whenever I see the Grand River here.
What inspired you to become a scientist?
I first became interested in science in middle school. I was inspired by my biology teacher who taught us about the tissues and cells of our body and how specialized they are for their functions in the body. I also had a picture book with photos from an electron microscope of different types of cells. I loved looking at that book and became curious about cells and biology.
Did you really start to be drawn toward science after high school?
Yes, when I was a student studying at József Attila University in Szeged, I began to gravitate even more toward science and decided I wanted to work in a lab. I met a professor who was working on cartilage, explaining how it functions in the body, and how it has such unique physical properties and how all this depends on gene regulation. This got me interested in studying how cells function to make cartilage.
I eventually learned how the DNA-packaging programs cells to become a certain tissue. It all started with trying to understand cartilage and how it works. I received my Ph.D. studying tissue-specific gene regulation. The important question we asked was, “How are cartilage genes switched on in cartilage cells?” We isolated those cells and identified small regions in the DNA, called enhancer elements. We also identified protein molecules that recognized and bound to the enhancer elements and switched certain genes on specifically in cartilage cells. These genes made the proteins that give the characteristics to the cartilage tissue.
Where did you do your postdoctoral work?
I did my postdoctoral research in Los Angeles at the Beckman Research Institute of the City of Hope Cancer Center. That’s where I began researching genomic imprinting. In the case of imprinted genes, one copy of a gene is silent and the other is switched on. This process depends on which copy came from the mother and which copy came from the father. I became fascinated by why this difference can take place in the same cell even though the DNA sequence is the same in the two copies and the protein molecules are the same in the cell’s nucleus. I wanted to understand how the cell knows which gene copy comes from the mom and which comes from dad. It turned out that the two copies are packaged differently by DNA methylation and those differences originate from the sperm and the egg. Our work revealed how the cells recognize a difference in DNA methylation between the two chromosomes.
What made you decide to move your life to Grand Rapids and continue your career at the Institute?
I came to the Institute in the fall of 2014 because I wanted to work and collaborate with Dr. Peter A. Jones. I knew that he was setting up a very special place for epigenetic research in Grand Rapids, and what he was doing sounded very unique.
How would you describe what you do to someone who isn’t a scientist?
I was just explaining what I do to high school students at Van Andel Education Institute, and I told them I am in the “packaging business.” I work with DNA, which is the same in every cell, but each cell does something unique with it. This happens because DNA is packaged differently depending on the cell type. This packaging not only gives DNA its structure, but it also gives it instructions on how it is supposed to work. I look at how DNA is packaged. I study DNA methylation, transcription factors, and histone modifications, which are epigenetic mechanisms that create signals that turn the switches “on” or “off” for each gene. In the case of imprinted genes, packaging depends on the parental origin of the chromosome. One interesting question we are looking into is how the initial genomic imprints are reset in each generation in the male and female germ lines, how the sperm and egg package the DNA differently.
Are you interested in how DNA packaging and these epigenetic signals might play a role in diseases?
Yes, I study how cells recognize this packaging material, and how the molecules that are packaging the DNA work. I mainly focus on something called “global changes” or complete re-packaging in cell reprogramming and human development, which only happens two times during life. One time is in the early embryo right after fertilization, and the other is during germ cell development 3/4 the process that leads up to the zygote. The question I am asking is, “What are the epigenetic changes that affect the very beginning steps of human life?” My approach involves epigenome mapping but also genetics, where we use tools to remove one packaging component and test how this affects the fate of the cell and development.
What do you see on the horizon for your field?
What fascinates me are the mechanisms of how things in the epigenome are related sequentially and what molecules are responsible for the changes that occur during development. It’s important to understand how these epigenetic and genetic changes play a role in normal human development. Scientists will eventually complete an atlas of all the packaging landscapes of all cell types, at all developmental stages in health and disease, and we will also have a database about how everything is related functionally. This information will help us understand diseases better, which could lead to new treatments and prevention for many diseases.
How can donors and philanthropy help support your research?
Support from donors helps so much. Philanthropy helps us to do research that is outside of the box. With philanthropic support, you can do something more adventurous than normal, especially when you don’t have a lot of preliminary data to apply for a grant. Philanthropy can also help fund the gathering of this preliminary data that we can use to get larger grants.
What do you do in your spare time when you’re not working with genetics and epigenetics?
I really like to play my cello. I feel very lucky that St. Cecilia Music Center in downtown Grand Rapids has a chamber orchestra where I can play with other string players once a week. I also love to ride my bicycle with my family and I am always looking to go out and ride the trails in Michigan. I like riding through forests and next to rivers.
What gives you hope for the future?
When I think about the future, I immediately think about the next generation. When I see young people who are smart, curious and passionate about their studies and also about issues in the society, then I am hopeful for the future.