What? – A detailed description of what you did during your STEP experience.
I chose to do undergraduate research as my STEP experience. I spent the summer in the lab of Dr. Gustavo Leone in the department of Molecular Virology, Immunology, and Medical Genetics in the OSU College of Medicine. I have been a member of this lab since February 2013, but this is the first time I have had my research funded and my experiences this summer has formed me into a better researcher and has shown me that I want to pursue research in my professional life.
Having been previously trained on basic molecular biology research techniques (mammalian cell culture, SDS-PAGE, qRT-PCR, microscopy, etc.), I came into the summer already working on a project. The focus of the lab is studying how PTEN (a tumor suppressor gene) stability in the tumor microenvironment influences tumor growth. We are looking at breast cancer etiology, specifically at fibroblasts as this cell type makes up a large portion of the tumor microenvironment (also called the stroma). Fibroblasts are spindle like cells that secrete components of the extracellular matrix (e.g. collagen) that allows cells to adhere and grow more efficiently as well as communicate. It had been previously discovered that fibroblasts are somehow changed morphologically to actually increase the amount of collagen produced and that this alteration in the ECM promotes the growth of cancer cells. The Leone lab has attributed at least some of this change to loss of the PTEN tumor suppressor in these fibroblasts. Going into the summer, we had already identified a list of about 50 genes that have been shown to destabilize or degrade PTEN protein in MCF10A cells (a normal mammary epithelial cell line) and we began testing these genes in fibroblasts using RNAi technology. RNAi is a relatively recent technology that disrupts the production of mRNA from DNA in a process called transcription. This effectively “knocks down” the gene of interest and we can then observe the physiological and biochemical changes that result from loss of this gene. This is how I started my summer–knocking down genes and running western blots and real-time PCRs to confirm the gene knockdown and observe any effects on PTEN levels.
The direction of my research actually changed during the summer to focus less on the fibroblasts and more on the epithelial cells (the cell type that lines the surface of organs throughout the body). This shift in focus occurred for a couple of reasons, partially because we had received more promising results in this area and partially because Dr. Leone wanted us to move forward with creating knockout mouse models and focus less on the cell culture aspect of our research. This is what I have been working on the majority of the summer. I became trained in working with mice and began perfecting my technique in genotyping and handling them. Currently we are breeding three different lines of mice to knockout three of the most promising genes that our research has uncovered. As far as we know, no other lab in the world has created full body knockout mice for the genes we are looking at (we will be the first). We have even discovered that one of the genes we are looking at creates a visible phenotype upon knockdown; the mice are approximately half the size of their litter-mates at all stages of life. We are still breeding all three lines to get the correct genotype, but we are making progress. We are simultaneously performing embryo studies to see if these knockout mice are even viable (sometimes loss of a gene important in fetal development results in termination of the pregnancy before birth). I am ecstatic at the results I have obtained this summer and am grateful to the STEP program for making this research possible.
So What? – A personal response to your STEP experience, including feelings, thoughts, judgments, and what you have learned about yourself and your assumptions from what you did and how you reacted.
Research is a required component of my major, but I would be in the lab even if it wasn’t. I have learned a lot about myself as a person by being in a research lab. After I graduate, I would ideally like to enter an MD/PhD program to be able to work in both clinical and academic settings. The research I am doing shows me how these two aspects of medicine are really married together. Clinics treat current patients while the academic research labs try to prevent future patients from developing. I would love to be able to spend half of my day on the floor in a hospital and spend the other half heading up a lab working on some of the conditions I see in the clinic.
There are some aspects about myself I discovered that I did not know going into the summer. First and foremost, I am willing to put in the time demanded by research. Many times over the summer I far exceeded the typical 40 hour work week, even coming in on Saturday’s for most of the summer to make sure all of our experiments got done. It has made me wonder whether or not that is the kind of life I would like to lead in the future, but for now, I wouldn’t want it any other way. Being in a lab has taught me to think critically and to question my own data in order to obtain appropriate and well thought out conclusions. The mentoring I have received from my PI has been superb and when I compare myself today to just a couple of years ago, it is astounding to see how much I have grown as a scientist.
Now What? – Discuss how the things you experienced and learned during your STEP experience will affect your academic, personal, and life goals moving forward.
The research I conducted this summer will be used as a jumping off point for the research I will conduct for the last two years of my undergraduate education at Ohio State. Participating in the STEP program and conducting research during my undergraduate career at Ohio State has confirmed for me my professional career goals and has sparked an interest in me conducting cancer research for the rest of my life. I thought I wanted to pursue a career as both a physician and a basic scientist, and conducting research and shadowing at the hospital has confirmed for me that this is life and career I want. Without funding from STEP, conducting research year round would have been very difficult for me. I am grateful to the program for providing this awesome opportunity for undergrads and I hope the program continues to promote success amongst OSU students.