David Nhu Nguyen Ph.D.
Postdoctoral Fellow, Lewis Laboratory
Stanford Medical School
Reflections from the Fellowship Year
I am honored to be the first recipient of the Controlled Release Society’s Joseph R. Robinson Postdoctoral Fellowship, and I would like to share some insight into my experiences. Foremost, I am very grateful for the support in research and medical training that I have received as a direct benefit of this fellowship. I cannot continue to thank enough the CRS Fellowship Committee and benefactors of the CRS Foundation. My tenure has been fun and rewarding. More than just a year of training, the fellowship has connected me to many areas of research and mentorship that will serve me for the rest of my career. I was able to broaden my expertise and learn the conduct of basic biology and immunology research. I interacted daily with physician scientists. I was also able to support a year of medical training at Stanford University. Because of my year as the Robinson fellow, I have developed a more focused and sure trajectory for my future career and am looking forward with less trepidation and more confidence.
Investigating How a Novel Vaccine Adjuvant Activates Immune Responses
I joined the laboratory of David Lewis, M.D., who is a pediatric immunologist and focuses on neonatal T-cell development, early immune responses, and influenza vaccination. I worked on a project investigating how a novel vaccine adjuvant activates immune responses. Members of the Lewis lab had previously shown that immunization with commercially available preparations of influenza vaccine together with a cationic lipid plasmid DNA complex (CLDC) could activate both humoral and cell-mediated immune responses. However, there was much debate as to how this CLDC actually triggers greater immune responses than those with simple vaccination alone. Further, this nanoparticle complex had recently entered early phase I clinical trials, making these investigations all the more relevant and interesting.
In particular, I worked to discover the mechanism of interaction of this CLDC nanoparticle with innate immune receptors. I spent much time learning basic immunology techniques, many of which I had previously been exposed to, but working in the Lewis laboratory allowed me to develop a greater understanding of the fundamentals of these techniques. CLDC particles likely enhances vaccines through multiple mechanisms, including activation of the innate immune response. We hypothesized that the noncoding plasmid DNA in the CLDC was recognized by an intracellular receptor of DNA. Since there are multiple known and hypothesized distinct receptors of DNA, we began by showing that this CLDC does not appear to activate toll-like receptors (TLRs). A recently described pathway involves both DNA and an RNA intermediate in intracellular DNA recognition. We were able to show that, at least in part, CLDCs can trigger innate immune responses through this DNA/RNA pathway. I was able to characterize the magnitude of this response in both cultured cell lines and primary human immune cells. Currently, most of my research work has been put on hold since I have entered into the in-hospital clinical training part of my M.D. program. However, I plan to return to the laboratory this winter and spring to finish up these investigations, including in vivo investigations, and look forward to publishing my results.
As a Joseph Robinson fellow, I was able to choose any laboratory based purely on my interests and less on available funding. This allowed me to pick a laboratory in a field for which I have no formal training. During my time as a student and postdoc at MIT, I had worked extensively with developing novel materials for delivery of DNA vaccines, siRNAs, and immunostimulatory RNAs as vaccine adjuvants. I had much experience in the development of novel materials and the formulation and characterization of micro- and nanoparticles, and I also had some limited experience in characterizing innate and adaptive immune responses. Since Stanford is a world-leading expert in the field of immunology, I hoped to broaden my horizons and learn more about immunology from the perspectives of biological studies, medicine, and physiology. I believe that with a good grasp of the fundamental biology and physiology I will be more capable of engineering systems that take advantage of immune responses in my future career.
The practice of medicine and conducting laboratory-based research could readily be two careers on their own. Both require the dedication of extraordinary energy and philosophy. While both fields might antagonize each other with respect to time and resources, in the end, the goal is still the same—advancement of society by promoting health. I was able to find a lab with multiple members who are also physician scientists, splitting their time between clinical work and laboratory work. My year as the Robinson fellow exposed me to mentors and role models with career trajectories similar to my own. One of the most important aspects of career development is learning both from your own experiences and from the experiences of others. Working side-by-side with physician scientists, some established and some still in the process of establishing their careers, I have gained much insight as to how I may personally approach this daunting choice of career paths. I have come away with a greater understanding of how to align myself and my future medical training (residency and eventually fellowship) in such a manner that I will be well-situated to advance into the role as junior faculty. In short, I gained an appreciation for how to balance personal life, clinical duties, and research goals, and it is this experience that I will carry with me throughout my career as a physician scientist.
Even though my time as the Robinson fellow is up, I will continue to enjoy the benefits of this 1 year postdoc experience. Over the course of the coming 6 months, I will be applying to residency programs in internal medicine. Over 3 years of residency, and additional time in a subspecialty fellowship, I will undergo more intensive and focused medical training that will become the basis for my future practice in medicine. I currently plan to enter fellowship training in infectious diseases. It is during those years of medical fellowship training that I will have the opportunity to return to laboratory research and establish new lines of investigation.
Long term, I plan to merge my experiences in medicine with my background in nanoparticle technology and immunology. I have developed a unique set of training in materials engineering, drug delivery, immunology, and the practice of medicine. My future career will be dedicated to understanding nanotechnology in medicine and designing nanoparticle-based medicines for battling infection and controlling—activating, suppressing, or redirecting—immune responses. Our current knowledge of the safety, reliability, and function of nanoparticles in vivo is still limited in animal models and even more immature in clinical use. As the field progresses, I will gain expertise in how nanomedicines interact with the human body. Using this knowledge, I hope to engineer new systems for delivering vaccines, investigate new vaccine adjuvants, develop novel antimicrobials, and combat autoimmunity.
Finally, I strongly believe that no matter how successful I am as a clinician or productive I am as a scientist, my most influential role will likely be as a teacher. Like Prof. Robinson and all of my mentors, I am excited to share my cumulative experiences with future generations and look forward to embracing this role in the hospital, in the laboratory, in the classroom, or wherever else my career takes me.
The CRS Foundation’s Joseph R. Robinson Postdoctoral Fellowship was
presented to David Nhu Nguyen at the 36th Annual Meeting & Exposition of
the Controlled Release Society in Copenhagen, Denmark, July 2009.
The research was conducted in 2009 and 2010.
Many thanks to the CRS Foundation donors who made this fellowship possible.