Duchenne muscular dystrophy (DMD) is a lethal, X-linked, childhood-onset degenerative disease caused by mutations in the dystrophin protein, which is responsible for maintaining muscle integrity and function. The prolonged occurrence of degeneration events in dystrophic muscle leads to chronic inflammation, insufficient repair and the progressive loss of muscle mass that is replaced by fibrosis and fat, leading to significant mobility impairments and loss of ambulation. There is currently no cure for DMD, but there are drug and gene therapy efforts to convert the disease to a milder but more inflammatory form of dystrophy. One novel approach we have been studying is to modify immune cells, particularly macrophages, to prevent muscle loss and promote regeneration. Finding effective and targeted immunomodulatory treatments that can re-program inflammation and bias it toward regeneration without systemically suppressing the immune system is a major unmet clinical need.
Our research aims to understand the mechanisms controlling regenerative inflammation in acute injury and dystrophy, specifically focusing on the role of recently discovered macrophage subtypes and their secreted growth factors. One of the highlights of our work is the discovery that these macrophage subsets guide the formation of structurally distinct damage-clearing and regenerative inflammation tissue zones. Our compelling high-dimensional data — single-cell and spatial transcriptomics — and advanced imaging techniques indicate that these layered regenerative tissue zones are sensitive to intermittent glucocorticoid immunosuppression (current DMD standard of care), and that they can be easily detected using a validated antibody panel and thus warrant the reevaluation of other current DMD-focused treatments on muscle regeneration. The work performed in Laszlo Nagy’s lab at the Institute for Fundamental Biomedical Research at the Johns Hopkins All Children’s Hospital highlights the importance of macrophage-organized regenerative inflammation tissue zones, and their targeting can be potentially exploited to improve outcomes in DMD.
Questions & Answers
Why did you choose Johns Hopkins for your work?
I chose Johns Hopkins for my postdoctoral training because of its exceptional reputation as a research institution that conducts world renowned, groundbreaking research while fostering a collaborative environment.
Johns Hopkins offers an extraordinary environment, great infrastructure and abundant resources to do top-notch research. Moreover, my research interests were aligned with Professor Nagy’s research topics, and the Department of Medicine features a diverse group of labs that investigate the role of the innate immune system in disease and disease progression. I am immensely proud to be part of this supportive scientific community.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
It is an incredible privilege to receive this award in honor of Paul Ehrlich, a Nobel laureate who conducted groundbreaking research in the fields of hematology, immunology and chemotherapy. Ehrlich’s enormous contributions to understanding immune responses have influenced the fields of immunology and medicine for generations, leaving behind an enduring legacy. This award inspires me to continue my academic journey in harnessing the power of the immune system to resolve tissue injury and promote regeneration. Being in the company of great scientific minds who have received this award humbles me.
What contributed to your project’s success?
In my view, mentorship and collaboration are two critical factors for achieving success in science. My mentor, professor Laszlo Nagy, has been an unwavering source of support both personally and professionally, offering invaluable advice, training and collaborative opportunities, and resources. Professors Nagy and Timothy Osborne, our institute’s directors, have consistently demonstrated the importance of maintaining curiosity and enthusiasm for academic research. Additionally, I have had the privilege of collaborating and working alongside exceptional graduate students, lab technicians, postdoctoral fellows and senior faculty from multiple labs across various universities, such as Laszlo Halasz, Darby Oleksak, Xiaoyan Wei, Lee Sweeney and David Hammers, among many others.
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?
Young Investigators’ Day is a special occasion in the Johns Hopkins community, dedicated to celebrating the accomplishments of trainees. Such events play a significant role in fostering a sense of recognition and appreciation among trainees. It’s worth noting that the success and impact of research are often attributable to the perseverance of students and fellows who relentlessly push forward. While the journey can be both rewarding and thrilling, it demands unwavering dedication and countless hours of hard work. Therefore, I am thrilled that Young Investigators’ Day acknowledges and honors the tireless efforts of trainees who contribute to pioneering research at Johns Hopkins.
What has been your best/most memorable experience while at Johns Hopkins?
One of my most memorable experiences at Johns Hopkins was when my colleague, Laszlo Halazs, and I successfully implemented our high-dimensional data integration pipeline into our workflow. It took us months of rigorous testing, coding, debugging and troubleshooting to find the right parameters and bioinformatic tools that could overcome the technical constraints of the technology. Ultimately, our efforts bore fruit, enabling us to enhance our data set’s resolution and uncover the immune cell landscape of acute injury and DMD-associated pathology. I cannot stress enough the significance of Laszlo Halasz’s bioinformatic expertise in driving this project forward.
What are your plans over the next year or so?
In the short term, I intend to publish the research findings presented here, wrap up other ongoing projects and submit applications for development grants that will facilitate my transition toward independence. As a recent recipient of my U.S. permanent resident card, I am looking forward to advancing on the academic ladder, and I am optimistic about the prospect of seeking faculty positions in the next year. My ultimate goal is to establish my own laboratory, advance the field of tissue repair and regenerative inflammation, and continue making significant contributions to the scientific community.
Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?
Practicing archery is a passion of mine. I have competed at an international level with the Cyprus national Olympic recurve team, and archery serves as my primary leisure activity outside of the laboratory to maintain my mental and physical well-being. Archery allows me to hone my focus, clear my mind and remain committed to achieving my future objectives.