Research Department: Neurology and Neurotherapeutics Graduation Date: May 2019
Abstract: Stroke is the third leading cause of death and disability in the United States, affecting 795,000 Americans each year. Currently, the only efficacious, FDA-approved treatment for stroke is Tissue Plasminogen Activator (tPA), which is only used to remove (“bust”) an existing clot within the first 4.5 hours after the onset of stroke. While tPA helps prevent further damage, there is no therapeutic to help facilitate repair and recovery. A promising area for developing a therapeutic revolves around understanding and regulating immune cell activity in the brain following stroke. After a stroke, the immune system is activated, which leads to an influx of immune cells into the brain through the blood-brain barrier, exerting both pro-inflammatory and anti-inflammatory effects. Of the cells that migrate into the brain, B-cells are a specific subtype of lymphocytes that have been shown to be neuroprotective, as seen in work done previously in the Stowe lab. These neuroprotective B-cells have been shown to endogenously produce neurotrophins and pass through the blood-brain barrier. Because neurotrophins are proteins that induce survival, development, and plasticity in neurons, the use of neurotrophins has been shown to help with post-stroke recovery. Here we focus on assessing the effects of the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) when combined with the neuroprotective nature of B-cells. As seen in previous clinical trials, intravenously-administered BDNF is ineffective due to its extremely short half-life (on the scale of minutes) and its inability to cross the blood-brain barrier. Here we propose that B-cells that are genetically modified to overproduce BDNF may work as a suitable source to continually produce BDNF to help with neuronal recovery after stroke and potentially serve as a means to deliver BDNF directly into the brain when injected intravenously.
What does research mean to you? As cliché as it sounds, research offers the opportunity to seek out answers to the most pressing problems facing society today. However, the most fantastic aspect of research is that it speaks to everyone differently. From talking to others involved in research, I have realized that everyone has their own motivations for getting involved in research. Some people get into research with the mindset of potentially helping millions of individuals. Others enjoy the challenge and discovery that research offers. Many people fall in-between or even pursue their own unique goals and aspirations. Despite one’s motivations, I realized that research is supposed to be fun. Research is an opportunity to have limitless enjoyment while you tackle the leading problems at the forefront of your respective fields. It feeds my curiosity, helps me grow, and even drives me crazy from time to time. However, at the end of the day, research has always been an enjoyable experience that keeps me coming back for more (even on the weekends!)
Tell us about your journey. One of the most appealing aspects of college that spoke to me was the ability to get involved in research. In high school, I always felt like everything I was doing was limited to this small bubble. Coming to college and having the opportunity to pursue research, I felt like the chance to get involved in something bigger than myself and make a significant impact on the world. Anyone reading this will probably think of me as naïve at the time, and I have to agree! Although it may seem like a far-off dream, that bright-eyed enthusiasm inspired me to talk to my NATS professor and get my first position as a research assistant in Dr. Christa McIntyre’s lab freshman year. Granted, as I gained more experience and matured I tempered my enthusiasm; however, I made sure never to lose that initial spark. That enthusiasm kept me going forward, as I later moved to Dr. Mario Romero-Ortega’s lab in my sophomore year and then into the Green Fellowship.
Deciding to apply to the Green Fellowship was no easy decision. As a five-month internship away from classes and my journey to pursue medicine, the idea of participating in the Green Fellowship did give me pause at first. However, I felt like I had to answer the question about whether an M.D./ Ph.D. was the right path for me. Ever since I joined my first lab in college and fostered my interest in research, I have always tussled with the idea of pursuing an M.D./ Ph.D. The more I went back and forth on applying to the program the more I realized that this Fellowship provided a once-in-a-lifetime chance to put my question to the test. What better way to find the answer to whether research is right for you than working as a full-time research assistant for 40 hours a week, without the worrying about academics!
Looking back, I have no regrets in deciding to pursue the Green Fellowship. Although I have decided that I do not want to pursue a Ph.D. or M.D./Ph.D., the experiences I have had and the incredible individuals I have helped me grow into a better professional. Although I am not pursuing a Ph.D. or an M.D./ Ph.D., this fellowship has helped me realize that I do sincerely enjoy research. If possible, I plan to seek out more research opportunities in the future.
Advice for Future Green Fellows
Fellowship, I would suggest creating your 4-year plan ahead of time. If you have an especially strict major (e.g., Biomedical Engineering), it can be hard to take an entire semester off for research without careful planning. Take the time to talk to your advisor about your interest in the program and plan to have a free spring semester. In the end, if you decide not to pursue the Green Fellowship, you have the opportunity to use that semester to study abroad or take exciting classes on campus!
If you are like me when I applied and are not sure about whether this research internship is the best path for you, my number one suggestion would be to talk to a professor, advisor, or even trusted friend. Be sure to ask them to play Devil’s Advocate and challenge your goals/aspirations/way of thinking. I took the time to talk to two of my most trusted professors before I decided to apply. When I had to verbalize what I was feeling and debate the pros and cons of participating in the program, I gained clarity on the situation and ultimately decide to pursue this opportunity. Be careful! This fellowship is a five-month commitment to working full-time in a research lab, so be sure that you are choosing to pursue this opportunity for the right reasons.
When in the program the only advice I can give is to be ready to have your socks rocked off (in a good way)! Transitioning from the life of a student to a full-time researcher can be jarring at first, so give yourself some breathing room and understand that no one expects you to have all the answers on day one. As you go through the program, I believe that all of my fellow Fellows (yes, I did that on purpose) and I can say that failure is something you cannot avoid. When I was going through this program, this was the hardest pill for me to swallow. In all honesty, this piece of advice is hard to completely comprehend until you are actually in the program. When you find yourself in this position, don’t be disheartened! I promise that you are not alone.
At the end of the day keep an open mind, seek out new opportunities, and have fun! The Green Fellowship is a once-in-a-lifetime opportunity so don’t forget to enjoy yourself. If you ever feel like research is starting to become a chore, take the time to reflect as to why you are feeling that way and talk to someone about it. If you have any questions, feel free to reach out ([email protected]). I wish you all the best going forward!