I worked in the lab of Mary Armanios, M.D., where we discovered a new genetic cause of familial pulmonary fibrosis due to a mutation in the nuclear RNA exosome targeting component ZCCHC8. Our lab efforts are focused on elucidating the genetic underpinnings and mechanisms of lung disease, cancer and telomere syndromes. Specifically, my dissertation focused on identifying new genetic causes of pulmonary fibrosis, which affects upward of 100,000 people, with over 30,000 deaths in the U.S. annually. For this work, we initially found that affected individuals in a family with autosomal dominant pulmonary fibrosis had both short telomeres and low levels of the telomerase RNA component. Using cells from these patients, and a CRISPR knockout mouse model, we found that ZCCHC8 is required for telomerase function and telomere length maintenance. In contrast to the ZCCHC8 partial loss found in patients with pulmonary fibrosis, we also found that complete loss of ZCCHC8 causes pervasive RNA dysregulation with misprocessing of other low-abundance RNAs including cilia components. In vivo, this biallelic loss manifests as neurodevelopmental disease. Our discovery identifies novel regulators of telomerase function that are mutated in disease and underscores the important role telomerase dysfunction plays in pulmonary fibrosis susceptibility. It also provides a model for studying the role of RNA misprocessing in the susceptibility to neurodevelopmental disease.
Questions & Answers
Why did you choose Johns Hopkins for your work?
The people. I remember walking away from my M.D., Ph.D. interview with a deep sense of the camaraderie among the students and faculty. People came here to engage in rigorous work and to be part of a team. Now, as I complete this part of my journey, I can honestly say that the experience exceeded my expectations. I was fortunate to have had the opportunity throughout my time at Johns Hopkins to learn from and train with diverse and collaborative mentors and peers in the hospital, across research labs, and within the Baltimore City community itself. The people work hand in hand with respect for one another, and I hope to take that with me along my professional journey.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
This award is a reflection of teamwork and dedication from many individuals both in and outside of Johns Hopkins. Most importantly, it gives a scientific voice to the family who participated in this work. We hope that these families and others struggling with diseases like theirs throughout the country and world may find answers if we continue to strive for innovative answers to critical clinical and laboratory questions that will advance our understanding of disease. As a pharmacist and researcher, Dr. David Macht asked critical scientific questions at the bench to address problems in human health, including lung disease, that we continue to confront today as exemplified by his attempts to discover antispasmodics in asthma by studying pig bronchi. I hope to model my physician scientist career in a similar fashion by advancing our understanding of pediatric neurologic disease both in the clinic and at the bench using innovative models as well.
What contributed to your project’s success?
Guidance from my mentor, Mary Armanios, and support from my family and friends have been indispensable to the success of my work. Mary engrained in me the perspective that a balanced life outside of training and work is key to success at the bench. At the end of the day, a project is a project, but family and friends are there through thick and thin and help you reset, motivate and be happy, all of which create a foundation for success when tackling the project efficiently and with focus. I also have to mention that this project would not have been successful without the incredible scientists working across the numerous Johns Hopkins core facilities who work hard and invest time and thought into the project as well. Finally, I cannot think of a time when any faculty or student across departments did not make themself available to help navigate challenging problems that arose along the way.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
The Young Investigators’ Day brings people together from across the university to share new ideas and discoveries that often take months and years to cultivate. Having the opportunity to engage with each other scientifically beyond our own scientific bubble both jump-starts new directions as well as motivates each other to keep moving forward. Students and fellows are the future leaders in research who will represent Johns Hopkins for years to come, so an opportunity to celebrate our work together is a way to begin collaborations with and provide support for each other as we rise in our careers.
What has been your best/most memorable experience while at Johns Hopkins?
My thesis seminar day is easily my most memorable experience at Johns Hopkins. I was so proud of the work we do in the Armanios Lab and I was able to share some of it with so many people from various walks of life in the same room all to celebrate science. My grandma, aunt, uncle, cousins, parents, siblings, nieces and nephew, who all traveled from our small farm town in Ohio, along with my high school, undergrad, medical and graduate school friends, and finally my mentors from Ohio State and Johns Hopkins all gathered to learn about the telomere, RNA, and lung and neurologic disease and then eat and drink champagne in the same room!
What are your plans over the next year or so?
I will be completing a pediatric neurology residency at Boston Children’s Hospital and plan to care for and study the genetics and treatment of children with neurologic disease as a physician-scientist.
Tell us something interesting about yourself.
I am the second oldest of six kids who grew up on my family’s dairy farm in rural Ohio. I still get to go back on occasion and farm with my dad and brothers! My parents didn’t have the opportunity to go to college, so it makes my journey in medicine and science even more exciting as they are right there with me each step of the way seeing all of this for the first time as well.