Brian Brown, Biochemistry and Molecular Biology
“Synthesis of a Novel Set of Flexible Expanded Nucleoside Reverse Transcriptase Inhibitors”
Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and other RNA viruses pose a great danger to human health on both an individual and global level. Several current treatment options on the market have been designed to inhibit the polymerases these viruses use for replication, such as HIV’s reverse transcriptase (RT). By inhibiting the replication of the virus, the viral lifecycle is halted. However, many of these drugs have begun to fail due to the viruses developing drug resistance. The type of resistance focused on here is the development of point mutations in the active site of these target polymerases. These mutations introduce steric and electronic hindrance, reducing the binding affinity, and subsequently the efficacy, of previously developed reverse transcriptase inhibitors. This allows the virus to overcome drug therapy and successfully transcribe its genome for viral replication. As a result, new compounds are desperately needed that can overcome resistance in viral polymerases with greater efficacy. It is our hypothesis that by combining the already known activity of previously established antivirals, such as 2’-methyl modified guanosine, with structural alterations found to be advantageous by our laboratory in the past we will be able to design, synthesize and characterize a series of nucleosides that will maintain activity against resistant viral strains.
When and how did you find out that you could do independent research or creative work as a UMBC undergraduate?
Luckily, I knew about the opportunities afforded to undergraduate students in research at UMBC even before I started as a freshman. The Meyerhoff program helped to really drive home the importance and the benefit of starting research at the undergraduate level.
How did you find a mentor and decide on a project? How did you know this was the project you wanted to do?
I looked to professors whose courses I had taken for possible lab positions. After taking Orgo I with Dr. Seley-Radtke in the Fall of my sophomore year,
I knew I wanted to get involved with organic chemistry research in some capacity. Fortunately, Dr. Seley-Radtke had an open position in the lab and was willing to bring me in halfway through my organic chemistry sequence. From there, the work has grown on me exponentially! Every research project will have you floating in the doldrums at some point or another; that's just the nature of science. But even when I'm met with challenges in Dr. Seley-Radtke's lab, I don't get discouraged or feel like giving up; instead, it just drives me to work even harder.
How much time will you put into this research/creative work?
It varies from week to week, since some parts of my project require more attention than others, but on average I plan to put in 10 to 12 hours per week during the academic year and upwards of 40 during breaks. I got a head start on my project over the Winter break, so that helped me to maximize my time doing meaningful research during the semester instead of just learning the ropes.
What academic background did you have before you started on this research?
Because I entered a drug design lab after only completing one course in organic chemistry, I felt like I was stepping into some pretty new territory. However, because the course I just took appealed to me so much, every time I was met in the lab with new, confusing information to digest, I treated (and continue to treat) it as a learning opportunity. Now that I have finished the introductory organic chemistry sequence, I am able to better understand some of the finer details behind my project, and as I take more courses, my confidence in my ability as a researcher ought to increase as well.
What is your advice to other students about getting involved in research?
Start looking now! Put down your remote, go to your department's website, and look through the faculty pages for a professor whose work grabs your attention. Focus not only on doing well academically, but also on making connections with professors. The opportunities afforded to me have mostly all come about as a result of networking. If someone can put a face to your name and remembers you as a strong student who is truly passionate about getting started in research, you are that much more likely to receive an offer from a professor to do undergraduate research.
What are your career goals?
As I am gaining more experience in both the classroom and the laboratory, I am starting to really narrow down and refine what I see myself doing professionally. At the present moment, I am interested in the interface between the synthesis of novel drugs to combat HIV, etc. and the efficacy of those drugs against viruses in the human body. This still leaves a huge range of potential careers spanning basic research and clinical research. With time, I hope to discover where I feel most comfortable in that continuum, but in the meantime, I am enjoying my time in Dr. Seley-Radtke's lab making sense of the raw chemistry behind the big picture.