To summarize the work of my CURF fellowship, the inception of my research project began with the observation that the proteins TERT and STAT5 physically and functionally interact to increase the expression of pro-calcification genes in Calcific Aortic Valve Disease (CAVD). This insight revealed a novel pathway by which calcification develops in valvular disease and the potential for a new druggable treatment target. Our group hypothesized that the disruption of this binding interaction could attenuate calcification in cells of the aortic valve. Broadly, my task was to use standard molecular biology cloning techniques to engineer two plasmids that could be used to detect when TERT and STAT5 bind within cardiac tissue. Additionally, by detecting TERT-STAT5 binding, this tool offers a platform to test the efficacy of drugs designed to inhibit the TERT-STAT5 complex.
When I first discussed this project with my mentor, I was thrilled to embark on an assignment that seemed so straightforward. At face value, the steps involved seemed manageable and well-adjusted to the information I have learned in my undergraduate STEM courses. Additionally, by offering the promise of drug screening and development, I could envision a direct throughline between my work at the bench and patients in clinical settings, a translational prospect that excited me greatly. However, over the course of the CURF, I have realized that the research process is much more iterative than I could have imagined. While the overarching premise seemed linear at first glance, I could not expect the many moments in which I had to rethink my strategy, techniques, and design of the plasmids I was engineering. Although I was initially frustrated, I found that troubleshooting my failures helped me understand my project with a depth I would not have been able to attain otherwise. As I slowly made progress, I gained confidence in my abilities to design well controlled experiments and predict errors along the way. In my opinion, these soft skills are what truly advance your comprehension of the scientific method and that which improve your aptitude as a researcher.
Now that my time as a CURF fellow is drawing to an end, I feel honored to have discussed my experiences on the Honors College blog. I hope that these writings can help students who may be interested in embarking on their first research venture. Until I graduate next spring, I will remain in the St. Hilaire lab and continue studying TERT and STAT5 within CAVD. Working on this project has deepened my appreciation for the pathophysiology of valvular calcification and I hope to end my time having completed the construction of these plasmids. With regard to my graduate education, I have shifted my focus slightly since my first CURF post. Following graduation, I plan to immediately enroll in the MS in Clinical Exercise Physiology degree within the School of Education at Pitt. After that year, I will apply to MD/MPH combined degree programs to concurrently study medicine and public health.
As a pre-medical student with interests in fitness, prophylactic medicine, longevity science, and cardiology, I hope to forge a career that marries effective clinical care with the knowledge and skillset to apply interdisciplinary solutions that prevent cardiovascular disease at a population level. Exercise is perhaps our most potent "drug" for lifespan and evading the onset of chronic disorders. Unfortunately, many of us lack the guidance, resources, or literacy to design an exercise program for longevity. Obtaining my master's in clinical exercise physiology offers the education necessary to apply exercise in the prevention and management of chronic illness in clinical settings. I believe this program will make me a more informed practitioner and well-equipped to engage with an interdisciplinary cardiac team of physician assistants, nurses, and exercise physiologists as a future physician. Regarding the MPH degree, I am excited to gather a robust knowledge of epidemiology, environmental health, health policy, and biostatistics. Along with my clinical duties, I aspire to blend my degrees in public health and clinical exercise physiology to research, design, and implement exercise-related interventions that reduce the incidence and prevalence of chronic cardiovascular diseases.
With regard to scholarly endeavors, I plan to pivot to clinical and public health related research during my gap year. As I discussed in my second CURF blog post, the health sciences offer a wide variety of research opportunities. While I have thoroughly enjoyed basic science research up to this point, I am eager to try my hand in other modalities. At the time of this writing, I am interested in the socioeconomic determinants of health and how they dictate patterns of cardiovascular disease and patient outcomes following treatment, particularly in disadvantaged communities. As heart disease is the leading cause of mortality in the United States, I am restless to understand the factors that perpetuate poor cardiac health despite the well documented influence of physical inactivity, poor nutrition, and other lifestyle factors. That said, basic science research will always be close to my heart, and I would like to continue studying the mechanisms of cardiovascular disorders in medical school.
As you can see from this image, the overall sequence of steps in my project may look simple and linear. However, like any research process, it is important to continuously vet each decision, experiment, and result. Sometimes, your project can be cyclical, where you return to the beginning to rethink your design or strategy. Working through this exercise changed my expectations of my project and my perception of the research process overall.
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