STEP Reflection – Undergraduate Research, Gregory Nagy

  1.       My STEP Signature Project consisted of research on the plant Elaeocarpus japonicus, in which I extracted and separated chemicals found in the plant to see if any of the chemicals could work to fight cancer cells. This work was performed from May to July 2016 in the A. Douglas Kinghorn lab in Parks Hall as a part of the College of Pharmacy Summer Undergraduate Research Fellowship (SURF) Program. My day-to-day work included rotary evaporation, thin layer chromatography, column chromatography, liquid-liquid extraction, and collaboration with other lab groups to test our chemical fractions in bioassays.
  2.        My STEP Project was very valuable for my outlook on my professional career going forward. Without STEP, I may still have chosen to apply and participate in this research program, but STEP made it easier for me to participate. Going into the program, I had a strong feeling that I wanted to do research professionally. After the program, I know that I want to do research professionally, but I do not want to do the type of research that I conducted over the summer. I found that the work I was doing was important, but I thought that it was archaic in terms of the time that it would take to find new discoveries in the lab. I realized that what I really wanted to do was to use computer software to help expedite the drug discovery process. In my mind, the use of computer software, and the pairing of the computer modeling with real, ‘wet’ laboratory experiments, is the main thing that the pharmaceutical industry should be working on to churn out more drugs for society. I assumed that working with chemicals derived from natural products (fungi, animals, plants, bacteria) would be safer and easier to turn into official drug products. I had been taught in a spring 2016 Pharmacy class that natural products have some flexibility for being effective in the human body that synthetic products do not, known in the pharmacy world as ‘natural products can violate Lipinski’s Rule of 5’. I discovered over the summer that my inclination to favor natural products as the way of the future in medicine was overstated, and that I could accomplish more in my career working with computer software and synthetic pharmaceuticals than with natural products.

Through the STEP Project, I also understood that my goals for graduate school could not be accomplished at Ohio State, so I was able to broaden my horizons and plan to go out of state for graduate school, possibly to Seattle or San Francisco. This outlook has made me excited because I feel ready to take on such a large jump from my current experience as an undergraduate student. I also fostered a new sense of self-confidence and perseverance through the STEP Project. I learned the importance of not taking no for an answer, maintaining an enthusiasm and positive attitude about your work, and fighting for your cause/vision as I interacted with other people to collaborate on the research project. I was also able to interact with people from all over the world, because in the research lab there were students and faculty from Madagascar, India, and other foreign countries, so that allowed me to get exposure to different parts of the world, and appreciate the freedoms and opportunities that are present in the United States, which is partially why the international students and faculty are here in the United States.

  1.        In terms of shifting research perspectives, there were multiple events that led to my shift away from natural product research and toward computer-aided drug design (CADD). First, I realized that the work that I was doing in the lab wasn’t really going after our target disease: cancer. Yes, we were testing the fractions and samples from our plant against cancer cells, but we really weren’t aggressively trying to cure cancer. We would take the fraction and say, “Hmm, I wonder if this kills cancer?” It was a guessing game, a game of luck. We were at the mercy of the plant. If the plant decided to make some chemicals that humans discovered could kill cancer cells, then that was great. The problem was that the plant was still in control. The plant was the entity making the chemicals; humans could only get lucky in discovering the right chemicals in the plant to suppress cancerous tumors. In CADD, the humans are in charge of making the chemicals, so as a CADD researcher, I can go straight after the cancer cell and say, “I know that this drug I made can fight strongly against cancer.” In natural products research, the researcher goes up to the cancer cell and says, “A plant gave this to me. I’m not sure if it will kill you, but let’s give it a try.” I favor going straight after the solution to the problem, instead of relying on other entities to work hard, so I enjoy being in charge of the drug design process on the computer instead of relying on Mother Nature to grant humanity a medical cure.

My interactions with one graduate student in particular, Annécie, were especially of value to me. Annécie helped me realize that the chemistry will happen in the body according to the inherent laws of chemistry, regardless of the source of the chemical. That is to say, chemicals from natural sources are not inherently good, and chemicals from synthetic sources are not inherently bad; the effect is based on the actual chemical makeup and reactions happening in the body. This allowed me to free my mind of the restrictive focus on natural products, and think about applying to graduate school to study the method that I think makes the most sense: designing drugs with computer programs. Annécie is from Madagascar, and we talked about the privileges awarded to United States citizens, including with regard to owning a United States passport. These discussions helped me better appreciate the ability to travel, and the American mindset that anything is possible when you put your mind to it. She also pushed me to look beyond Ohio State for graduate school. My dad did both his undergraduate and graduate studies at Ohio State, so it took me a while to realize that that is not reality for most students. I started to broaden my horizons. Finally, Annécie pushed me to look at research labs doing this sort of computational work, and also to enroll in a computational chemistry class for AU16 semester, to see whether or not I would like the material. I enrolled in the class, which I would most likely not have done if it were not for her, and in the first six weeks, I have already learned valuable perspectives that will help me in my applications for graduate school. Another graduate student, Nikki, encouraged me to talk with Dr. Chenglong Li of the College of Pharmacy about his work in CADD. I was able to talk with Dr. Li and receive some important perspectives on searching for a graduate school.

In terms of fighting for my vision and not taking no for an answer, I tried to stay positive about my work. Since I was working on the plant, and the success of my experiments was in the hands of the plant and whatever chemicals it decided to produce, I tried to think positively, and keep a positive mindset as I conducted the research. I would joke with the graduate students in the lab that I would talk sweetly to my plant so that it would reveal useful chemicals to me. I actually ended up getting a result by the end of the ten weeks from one of my fractions, with respect to its ability to dismantle the electric potential on either side of a mitochondrial membrane, that is very impressive, especially for a fraction so early in the isolation process. I’m not saying that my positive thinking made this result happen; I am just saying that it helps to have a positive attitude and keep fighting even in the face of knowing that you might not get a great result. I also made sure to fight for my vision by advocating for my fractions to be tested against cancer cells. There were issues with the fume hood that delayed the testing against the cells, and I had to advocate for my project and push to have my cells tested, or, at least I thought that I was standing up for myself. At times, the reality was that I didn’t understand the timeline of the tests, but other times I think that I did have to stand up for my project to make sure that the fractions were tested against cancer cells. This persistence will help me be a maverick when I (hopefully) own my own biotechnology company in the future.

  1.              My shift from focusing on natural products to looking at CADD for a professional career is very significant. First, because I will be working on computers, theoretically I will not have to own as much equipment to start my own company, which will make it easier for me to actually start my own company. This is very important to me because I do not like the idea of someone else controlling what I do at work. I want to have the freedom to go after the professional goals that I really want to pursue. Second, I think that CADD is the way of the future. I want to be on the cutting edge of innovation for the biotechnological world. In my opinion, the cutting edge is the most exciting place to be, and I get really enthused about going after brand new cures and treatments. I think that I have found a niche which, when maximized, can be the next boom in the healthcare world. Using computers not just to discover drugs, but to model human cells, tissues, organ systems, etc., can COMPLETELY change our healthcare system. The ideal vision is a healthcare system where a patient sends in a cheek swab to a company, the company runs the cheek swab through the computer, creates a virtual patient in the computer, identifies every problem that is wrong with the patient, and has either a gene therapy or a pharmaceutical to fix that problem. In my opinion, the only way that society gets to that utopian healthcare vision is by using computers and computer software as the keystone of the movement. I am so glad that I fixed on CADD and protein/cell modeling at this stage in my life, because it will truly play a major role in the next revolution of health care. Third, I think that working in the biotech industry, specifically the CADD and biochemical modeling niche, will allow me to live the lifestyle that I want, in terms of work schedule, standard of living, and philanthropic impact on my community and beyond.

Interacting with a diverse group of people allowed me to further explore the idea of privilege and understand my ethnic, racial, gender-specific, and socioeconomic place in society. As a future entrepreneur, I need to be relentless and scrappy as I fight for the good of my company, and the good of society. Navigating collaboration in the College of Pharmacy as my project progressed was a small stepping stone to being able to dominate the biotech scene in the future, and make a lasting, positive impact for society’s health.

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Figure 1.My Test Tubes after LH-20 Column Chromatography Separation

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Figure 2.Thin Layer Chromatography Result after Running Silica Column Chromatography

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