Charting New Horizons in Medicine: An Inspiring Conversation with … – Yale School of Medicine

Stephania Libreros, PhD, brings her expertise to Yale School of Medicine as a recently appointed assistant professor of pathology and a valued member of the Vascular Biology Therapeutics Program. In this engaging conversation with Kanika Jain, associate research scientist at the Yale Cardiovascular Research Center, Libreros discusses her remarkable journey and unwavering passion for science.

Stephania (S): Originally hailing from Colombia, I am a Latina who relocated to the United States at the age of 14, where I subsequently completed my higher education. I attained my bachelors degree in molecular and cellular biology from Florida Atlantic University, where I actively participated in their renowned marine biology program. For my honors thesis, I delved into the study of chemokines and cytokines in tumorigenesis/biogenesis in breast cancer.

My journey in the field of science began with a limited awareness of the opportunities available to me as a minority and with limited financial resources. I was fortunate to encounter remarkable mentors during my scientific voyage who nurtured my passion for medicine and biology. My PhD mentor, Dr. Vijaya Iragavarapu along with Dr. James Hartmann, helped me gain confidence to pursue a career in science and academia.

S: My long-term research interest revolves around elucidating the complex molecular, biochemical, and cellular mechanisms that control inflammation and its resolution in humans.

During my PhD research, my primary focus centered on tumor immunology. Specifically, I delved into the investigation of how inflammation amplifies tumor growth under pre-existing conditions.

A pivotal moment in my scientific journey occurred when I became a member of the Society of Leukocyte Biology and attended my first scientific meeting. It was there that I had the privilege of witnessing my postdoctoral mentor, Professor Charles N. Serhan, receive the prestigious Bonazinga Award from the society. His seminar left a lasting impression on me and sparked my curiosity to learn more about how the activation of host endogenous mechanisms can control unwarranted inflammation. I found myself particularly drawn to the study of mediators that the body produces, to regulate inflammation, promote resolution and tissue regeneration, which was a stark departure from my PhD work.

S: Sure! My postdoctoral fellowship from the Harvard School of Medicine, was primarily focused on the structural elucidation of novel lipid mediators involved in the resolution of inflammation. These remarkable molecules, termed as specialized pro-resolving mediators (SPMs) (i.e. Resolvins), are potent immunomodulators of inflammation that can accelerate and enhance the host restoration of tissue homeostasis after an insult. A remarkable aspect of these mediators was their shared isobaric characteristics, which captured my attention. I homed in on the precise double bond geometry and alcohol positions within each molecule.

These structural nuances are fundamental for their stereoselective actions on human leukocytes, governing critical functions such as the augmentation of macrophage phagocytosis and the efficient clearance of cellular debris. My research delved into understanding the stereo-selectivity of these molecules and how it may orchestrate the resolution of inflammation using single-cell technologies in both model systems and human cells.

S: There were several compelling factors that led me to choose Yale. Yale boasts a rich history of fundamental discoveries in immune, cardiovascular, vascular biology and fundamental biology. This legacy allowed me to envision growing a strong rigorous program at the very core of disease research, with a focus on improving our understanding of the drivers of inflammation, its resolution and the elucidation of circuits that control this process.

Moreover, Yale is home to world-renowned experts in inflammation and cardiovascular biology, creating a dynamic and collaborative environment that greatly excited me. Yale's investment in long-term questions aligns perfectly with my passion for unraveling biological discoveries over the long haul. The close-knit relationships within the research community at Yale truly make it an epicenter of cutting-edge science.

Additionally, I was deeply impressed by Yale's commitment to diversity, inclusion, and equality. I was fortunate to participate in Yales Initiative of the Intersection Fellows Symposium (ISFS) in 2021. Yale actively strives to create an inclusive environment, and for me, representation is a fundamental pillar of scientific discovery and advances in medical research. I want my trainees to feel welcome and empowered, knowing that they are part of a supportive, inclusive, and diverse academic community. Im thrilled to call YSM, the Department of Pathology and VBT my new academic home, where I make advances in biomedical discoveries, while training the future generations of scientists and physician scientists.

S: It was amazing! I feel that the ISFS is a great initiative for postdoctoral trainees, especially those from backgrounds that have historically been underrepresented in academia. The ISFS provided me with exceptional career development opportunities to connect with a welcoming, diverse community of scientists nationwide and to obtain mentorship from faculty such as Wendy V. Gilbert, PhD, professor of molecular biophysics and biochemistry at Yale School of Medicine and David Dominguez-Sola, MD, PhD, associate professor of pathology, molecular and cell-based medicine at Icahn School of Medicine at Mount Sinai. It also provided an excellent platform where I was able to highlight my research accomplishments, future research program and diversity and equality initiatives.

S: Emerging evidence indicates that chronic, unresolved inflammation is an important underlying cause of numerous complex conditions such autoimmunity, asthma, metabolic syndrome, vascular diseases, neurological disorders, chronic infections, and sepsis. Therefore, there is an urgent need to identify novel ways to activate resolution pathways when they failed.

My laboratory focuses on understanding the role of the bone marrow in hematopoietic niches and how hematopoietic stem cell and progenitors contribute to the resolution of inflammation. We explore the regulators that dictate inflammation from the bone marrow, examining how different diseases affect the balance. Our research aims to pinpoint the stage at which the resolution of inflammation fails and to introduce pathways or circuits that can correct this failure. We will investigate whether the balance in the bone marrow is consistent across different diseases and explore the potential for introducing mediators to activate host resolution mechanisms.

The most exciting aspect of my role is the opportunity to uncover novel mechanisms behind these processes and potentially develop interventions to control excessive inflammation at its source. By understanding how the bone marrow influences the immune response, we hope to improve our ability to manage inflammation effectively since the birth of the immune cells.

S: It's important to note that virtually every known human disease has an inflammatory component. Therefore, there is an urgent need to harness the natural host resolution circuits.

Many of these circuits and molecules, such as the Resolvins, are derived from essential fatty acids, underscoring the importance of a balanced diet in maintaining health. Im also interested in discovering new resolution circuits and determining whether each organ has its unique inflammation resolution process, depending on its cell turnover rate.

Our ultimate goal is to decipher the switches governing the inflammation resolution mechanisms and provide the necessary mediators to facilitate resolution, thus enhancing the immune system's ability to manage inflammation more effectively. We also want to elucidate how we can correct these mechanisms, when they fail and lead to chronic unresolved inflammation.

S: What gets me out of bed in the morning is the sheer excitement of conducting experiments and making discoveries. I learned from Prof. Serhan that every day is a new opportunity to make a discovery. I also look forward to engaging in conversations with my colleagues, exchanging ideas, and being part of the scientific community. I hope to convey my enthusiasm for experiments and the unknown to the trainees in my lab.

S:Pursuing a career in medicine can be highly competitive, so it's essential to think about unique questions that truly excite you. Passion and enthusiasm are key; embrace the challenges and persevere. Don't let anyone or any setbacks diminish your love for science. Surround yourself with individuals who match your energy, support and empower your growth.

Seek out mentors who can provide diverse perspectives, and don't hesitate to celebrate your accomplishments, both big and small. Maintain a positive attitude and remember that experimental failure is not a reflection of you but an opportunity to refine your questions and experiments. Every experiment brings with it an opportunity to learn something!

S: During my undergraduate years, I had the unique experience of working with dolphins. It was fascinating to discover that human and mouse antibodies cross-react with dolphins and dolphins can contract diseases very similar to those affecting humans.

In terms of my personal interests, I've always had a deep fascination with butterflies and was even considering becoming an entomologist at one stage. This interest in nature and the question of "why" sparked my curiosity. I was particularly captivated by the incredible diversity within the same species. Science was always a passion for me; I recall hunting for butterflies as a child and using a dissecting microscope to examine the intricate patterns on their wings.

S: My fascination with butterflies started when I began to meticulously document the intricate patterns, vibrant colors, and varying sizes of their wings. I found myself intrigued by a curious observation: why do butterflies possess two distinct sides to their wings, with both upper and bottom part adorned with opposite patterns and colors. It was a question that sparked my curiosity.

I later learned that butterflies utilize their wings as a form of communication. The upper side is to attract potential mates while the lower side (wings closed) provides a clever camouflage against potential predators. I have always been fascinated by the diversity of nature, even within a kind, whether it is a species, a class, molecules or biological cells. The ability to document and share these discoveries with fellow enthusiasts who find the medicine and scientific discovery as exhilarating as I do, excites me!

S: Outside of work, I find solace in activities like meditation and yoga, which not only contribute to my wellness but also align with my scientific thinking. I am a certified yoga instructor and am keenly interested in understanding how exercise and wellness can regulate our bodys immune system.

Additionally, I enjoy cooking and baking, drawing inspiration from my father, who was a chef, and replicating flavors as if I were conducting experiments in the kitchen. My love for butterflies persists, and I continue to collect them, marveling at the wonders of nature.

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Charting New Horizons in Medicine: An Inspiring Conversation with ... - Yale School of Medicine