By Emily Leclerc, Waisman Science Writer
Epigenetics – the study of how environment can change and affect how genes function – was a new field for Phu Duong, PhD. Previously he had briefly studied electrophysiology. Then he jumped to blood stem cells for a short time before settling into epigenetics in the lab of John Svaren, PhD, professor of comparative biosciences and a Waisman Center investigator. “I became heavily interested in epigenetics and I also have a strength for computer science,” Duong says. “I also felt it was a great opportunity for me as a deaf person, to do computer science and epigenetics, because it is a deaf-friendly field.”
Duong was the first deaf person to be a part of Svaren’s lab. He was particularly intrigued by the work Svaren and his lab were doing and found it suited his interests well. Duong joining the lab brought some challenges as Svaren had not supported a deaf graduate student before. But both Svaren and Duong navigated the road bumps with grace. “It was sometimes a learning process for both of us as I didn’t get very good at sign language and sometimes things would get lost in translation,” Svaren says. “So, we had to make sure all the details came across. But Duong was always happy to be patient with all of the rest of us which was very helpful.”
Svaren and the other lab members welcomed Duong with open arms, some even taking the time to learn sufficient amounts of American Sign Language (ASL) to make communication easier. The lab as a whole smoothly adjusted to the accommodations Duong needed. UW-Madison also made access to those accommodations easy, Duong says. “UW’s McBurney Disability Resource Center is amazing at providing accommodations. I had interpreters for every lab meeting,” Duong says.
Svaren was equally as easy to work with. He was relaxed and straightforward, always ensuring the Duong had what was needed to be supported and successful in his work. “Svaren was always available to talk if needed. He is incredibly approachable,” Duong says. “He asked excellent questions. He knows how to clarify and get right to the crux of what you are learning or discovering. Over time he became more hands off because I was doing independent research and he allowed me my independence and allowed me to thrive in that way.”
The work that Duong was doing fits seamlessly into the overarching goal of Svaren’s lab. Svaren brought Duong onto a long running project that looks at what happens in Schwann cells after injury.
Schwann cells are the repairmen of the peripheral nervous system (PNS). When a nerve is injured in the PNS – which encompasses all of the nerves outside of the spinal cord or brain – Schwann cells activate and facilitate the cleanup of injury debris, the regrowth of axons, and the myelination of the new axons – or the coating of nerves with the fatty substance myelin. Schwann cells are also involved in the maintenance of already present myelin – which is important for proper connection and communication between neurons. These cells have been a long time focus of Svaren’s lab because of their regenerative abilities and their potential to help treat degenerative conditions of the nervous system.
Duong started looking at the changes that control how and when Schwann cells flip into repair mode. The injury repair protocols are always present in Schwann cells but they only become active after injury. Duong began investigating the role of a particular protein, BAP1, in the injury repair pathways. His last paper published in Svaren’s lab focused on BAP1.
The paper, Modulation of Schwann Cell Homeostasis by the BAP1 Deubiquitinase, which was published in the journal Glia, outlines Svaren and Duong’s interesting findings investigating Bap1’s role. Bap1 is involved in activating the injury repair pathways when they are needed. So, Svaren and Duong’s original hypothesis was that knocking out Bap1 would result in the pathways remaining inactive. But, the mice that had Bap1 knocked out presented with key injury repair genes prematurely activated and abnormal myelin. “We expected to see that after we removed Bap1 [the pathways] would still be repressed, even after a nerve injury. We saw the opposite result occur. After you remove Bap1, the [pathway was not repressed],” Duong says.
They also showed that Bap1 is an important component of myelin maintenance. Building myelin properly is important but so is maintaining it throughout the lifespan as degrading myelin will impair neuromuscular function. “The homeostasis phase for maintenance is really important,” Svaren says. “We think we found something that is really key for the maintenance of myelin.”
The work published in the paper provides important foundational knowledge of the processes involved in flipping Schwann cells into repair mode. Svaren is looking to push this work further in the hope of illuminating exactly what causes Schwann cells to switch the repair program on or off and how that switch can be manipulated. “There is very little known about the switch. And even though the peripheral nervous system is more regenerative than the brain, it is still not very good. So, we would like to be able to promote that regeneration,” Svaren says. “If we know the steps that make Schwann cells enter that regenerative state we can hopefully stimulate regeneration. Then I hope those lessons we learn in the peripheral nervous system for regeneration can also be helpful in the central nervous system.”
Supporting and mentoring Duong through his time in the lab has taught Svaren much about working with deaf individuals. Svaren feels that Duong has helped lay positive groundwork for working with more deaf or hard of hearing graduate students in the future. Today Duong is working in a postdoctoral position at the University of Rochester in Rochester, New York where he is studying markers of regeneration in Zebrafish.
Duong wants to thank Svaren, the Science and Medicine Graduate Research Scholars program at UW-Madison, the Cellular and Molecular Pathology Graduate Program (CMP) at UW-Madison, the Molecular Bioscience Training Grant through the CMP graduate program, UW-Madison’s disability offices, and his UW interpreter Paula for all of their support. He also wants to thank Emina Stojkovic, an investigator at Northeastern Illinois University that he worked under during his master’s program, for encouraging him to apply for his PhD.
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