Dr. Mark J. Zylka is the Assistant Professor in the Department of Cell & Molecular Physiology and UNC Neuroscience Center at the University of North Carolina, Chapel Hill. He received his PhD in Neurobiology from Harvard University in 1999.
Q: What prompted you to begin a career in research?
A: As a high school student, I was very interested in computers and science. One of my high school teachers, Robert Foor-Hogue, taught an independent research course. There was nothing like it anywhere else in the state, so it was truly a unique experience. We were able to pick a research project and see it through. It was during this time that I realized how fun, addicting and rewarding research could be. This class also gave me an appreciation for how research can positively impact the well-being of others. From that point on, I knew a research career was what I wanted to pursue. I didn’t know exactly what I wanted to study, but then what scientist does? We wind up studying new things all the time.
Q: What led you to specifically target Angelman syndrome?
A: One person—Dr. Ben Philpot. When I started working at UNC, my lab was primarily focused on developing treatments for pain. Ben and I have lunch together almost every day and talk science. His lab is very interested in Angelman syndrome and made several big discoveries with a mouse model of AS. We knew that patients with AS have sensory symptoms, so we decided to test the mice using the behavioral assays we have in the lab. Nothing came of those studies (yet). However, in the process, I had a lot of fun working with Ben. We now had even more to talk about at lunch, including brainstorming sessions where we dream up creative new ways of treating AS. We hope our current research pays off, but if it doesn’t we certainly aren’t at a loss for new ideas.
Q: What is your specific area of focus within the field of Angelman syndrome research?
A: In our collaborative work with Drs. Philpot and Roth, we found that a class of drugs called topoisomerase inhibitors can unsilence the paternal copy of Ube3a. My lab is trying to determine how these drugs turn Ube3a on. Since the ultimate goal is to test these drugs in patients, we need an objective way to determine how well the drugs are working. We cannot rely on symptoms in patients alone because they are so variable from person to person. To address this, we are searching for biomarkers that provide a more objective measure of drug efficacy. In addition, we are trying to better understand how Ube3a activity is regulated in neurons, and if Ube3a activity can be controlled with drugs.
Q: What have you learned through your research thus far, and what is the next step?
A: We learned that imprinting of Ube3a is not absolute. The paternal copy of Ube3a can be turned on in the adult brain. Whether this re-activation can be induced in the developing brain is an open question. Moreover, we do not know if topoisomerase inhibitors can rescue any of the physiological or behavioral symptoms of AS. These are questions we are actively investigating.
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Q: What is the single most rewarding aspect of conducting Angelman syndrome research?
A: The AS community is incredibly well organized. As a result, I sense a genuine personal interest in the research that my lab and all the other labs out there do. It is this personal interest, combined with positive feedback from the ASF and parents, that makes AS research particularly rewarding.
Q: How do you see your research complimenting the efforts of other Angelman syndrome or neurodevelopmental disorder researchers?
A: Our AS research lead us to a class of enzymes called topoisomerases. These enzymes are expressed throughout the developing and adult brain. Virtually nothing is known about the function of these enzymes in neurons. We hope that our research will shed new light on what these enzymes do, not only for expression of Ube3a, but also for expression of other genes that are found in neurons.
Q: Does your research focus on any other disorders?
A: Yes, my lab is also focused on developing treatments for chronic pain. Chronic pain affects a staggering number of people—25% of all Americans, making chronic pain more prevalent than heart disease, cancer and diabetes combined (statistics from American Pain Foundation). The drugs we currently use to treat pain have side effects and don’t work in a large number of patients. We are actively identifying new molecular targets for analgesic drug development. In addition, we developed several new therapies (drugs) that relieve pain in preclinical models. It is my long-term career goal to see at least one discovery made in my lab used in patients (be they patients with chronic pain or AS).
Q: What activities do you enjoy in your spare time?
A: I very much enjoy spending whatever free time I have with my wife and three year old son, from going out to dinner together to hanging out at the park and playing hide-and-seek. I also like to rollerblade early in the morning with my dog, to get exercise and stimulate random thoughts. I also enjoy gardening and watching things grow.
Q: Do you have someone in or outside the scientific community that has inspired you, or is there someone you look up to as a personal hero?
A: If I had to pick one person, I’d have to choose my grandfather as my personal hero. Although he passed away many years ago, he is still the first person that comes to my mind when I am asked this question. He sparked my imagination with his tales and stories, he inspired me to do my best, and his memory motivates me to this day, to continue to pursue all the things that enrich and bring joy to life.
See a list of Dr. Zylka’s publications., please visit: