For those applying to MD/PhD programs, you will have to complement your MD personal statement with a MD/PhD statement and a research statement. The research statement has a 10,000 character limit and serves to strengthen your argument why you want to do research and why you would be a good researcher. As an example, here is my research personal statement:
I initially became interested in research as an alternative to becoming a pharmacist because I wanted to actively search for new information rather than simply apply what is known. My experience volunteering at the University of Minnesota Medical Center (UMMC) helped me gain an interest in contributing to health care, which led me to wanting to do research that would have an impact on human wellness and understanding of the human body. As a freshman in college, I had wanted to work on synthetically designing novel drugs so that I could use chemistry to help improve human health. Although I was planning to do strictly chemistry research, a guest speaker for my genetics freshman seminar said he had availability for undergraduates in his lab so I jumped on the opportunity. This was an important decision that caused my vision for my future research to involve a broader spectrum of science.
My first research lab experience was in Scott Fahrenkrug’s lab in the animal science department at the University of Minnesota, which incorporated quantitative genetics, functional genomics, and genetic engineering to design methods for specifically inducing homologous recombination to create mutations in DNA. This research was applied to the design of transgenic animals such as a pig model for cystic fibrosis and cows lacking the growth hormone inhibitor gene so that they would produce more muscle per animal to potentially produce more meat to supply the growing world population.
I was involved in the research by performing much of the manual lab work for the assistant professor and lab supervisor, Dan Carlson. I cloned plasmids and verified their identity by gel electrophoresis, isolated RNA from tissue samples, and grew cells, lysed them and analyzed their DNA by PCR. I was able to learn vast amounts about the process of research and how my work contributed despite my limited knowledge of genetics and biochemistry that made it difficult to completely understand the mechanism by which we were pursuing our goal. I eventually understood how everything was connected in the lab: I made plasmids that were designed by Dan who would then put them into pig or cow cells to express the sequence-specific homologous recombination-inducing restriction enzymes that were either zinc-finger nucleases or transcription activator-like endonucleases (TALENs). The cells modified by these restriction enzymes had the potential to be cloned into animals to determine the effectiveness of the mutations.
I volunteered in the lab for the summer after my freshman year of college and was hired as a lab technician for the remainder of my time in the lab. Working in this lab helped me appreciate biology from a chemist’s perspective almost to the point that I felt like more of a biologist than a chemist. This experience made me excited about my future biochemistry and genetics classes where I was finally able to understand the general mechanisms of the protocols performed in the lab. By having applied a wide range of protocols, I found it easier to learn the biochemical mechanisms behind the research. This also made me more interested in topics related to our work in genetic engineering such as the possibility of using siRNA or miRNA to selectively turn off or reduce translation of certain proteins that could be potential methods for selectively targeting cancer cells based on their mutations. I learned to value the biological techniques involved in the lab’s research even though I do not want to focus my research on genetic engineering of transgenic animals.
Because I want to more directly contribute my work to medical research and utilize my chemistry background, I sought another lab position that would give me an opportunity to begin preparing myself for such a career. Therefore, I joined Natalia Treyakova’s medicinal chemistry research group in the cancer research center at the University of Minnesota in my junior year of college. The primary goal of the lab is to understand the role of DNA adducts in carcinogenesis by using the tools of mass spectrometry, organic synthesis, biochemistry, molecular biology, and computational chemistry.
My experience in this lab has helped me grow as an independent researcher because I was able to quickly comprehend concepts due to my strong chemistry background and previous experience in a genetic engineering lab. This experience helped me quickly become more independent in the lab. It has also improved my ability to communicate my results to others and practice creativity by designing my own project, going to lab meetings, presenting my research, participating in journal club, writing reports for Professor Tretyakova, troubleshooting, and receiving feedback from the other lab members.
When I started in the lab, I was placed to work with Teshome Gherezghiher, a post-doctoral student, to help him with his work on cyclophosphamide, a prodrug of a DNA alkylating agent, nornitrogen mustard. I learned how to perform the fundamental techniques used in the lab such as high-performance liquid chromatography and mass spectrometry while I was beginning to optimize the synthesis of standards for biological analyses. These standards had already been described in the literature, but I worked for four months to alter the reaction conditions to increase the yield of the reaction. I also synthesized an additional standard from one of the products of the reaction that had not been synthesized in the lab before and was not well characterized.
Over time, I have begun to understand how my work has contributed to more advanced analytical techniques. These standards are used to not only quantify the adduct formation and repair in cell lines in vivo, but they are also being used to quantify adduct formation in leukocytes isolated from donated blood that are treated with the drug. This can potentially be used in an ex vivo test in the clinic. Developing such a test to quantify adduct formation will hopefully contribute to personalized dosing of the drug, which is important because it has been shown that the sensitivity of the drug varies; this is the case in Fanconi Anemia patients who require a much smaller dose than other cancer patients without the disease to have the same amount of adduct formation because there are more defects in their DNA repair mechanisms. Without proper dosing of the drug, higher sensitivity patients may experience more severe side effects.
In addition to contributing to Teshome’s work on cyclophosphamide, I took on a project from a previous graduate student in the lab, Xun Ming, to study the occurrence of protein-DNA cross-links induced by cisplatin and their potential to facilitate mutagenicity and cytotoxicity. To our knowledge, cisplatin has not been previously shown to form mutagenic DNA-protein adducts. In his thesis, Xun showed how he had studied a cisplatin cross-link between lysine and guanine; he was successful at synthesizing a standard and was able to observe the cross-link in cells treated with the drug. He also wanted to search for guanine-cysteine cross-links that he determined to exist. Although he tried to synthesize a novel standard for the guanine-cysteine adduct, he struggled with its stability. Since December 2011, I have been trying to optimize a multi-step synthesis and purification method for this molecule.
When I synthesize and purify the standard without degradation, I will be continuing my research to search for the cross-link in cancer cell lines. Xun had hypothesized the cysteine-guanine cross-links migrate to guanine-guanine cross-links though the rate is unknown. The migration is believed to only occur with cross-links involving cysteine, but the formation of the specific adduct has not been confirmed. Observing the stability of the conjugate in cells will help determine whether the DNA-protein conjugates could potentially have a mutagenic effect. Also, verifying the formation of such cross-links in cells could help explain the effectiveness of the drug in certain kinds of tumors such as sarcomas, lymphomas, and some carcinomas based on protein interactions.
My research experiences have motivated me to learn more about cancer and become passionate about understanding its mechanisms and improving its treatment. Cancer is an incredibly complex disease; every cancer involves different genetic mutations resulting in alterations in the expression and structure of proteins – these mutations even vary within individual tumors. I am optimistic about the possibility to take advantage of these modifications to create personalized medicines that selectively target cancer cells to more efficiently and effectively treat cancer.
I plan on utilizing my undergraduate research experiences to propel myself into more advanced cancer research emphasizing in pharmacology and medicinal chemistry to contribute to the development of more specific anticancer medicines. I am inspired by the development of medicines such as the breast cancer drug Herceptin that targets cells containing a large abundance of the Her2 receptor that is characteristic of some breast cancers. Herceptin uses an antibody and has improved the survival rate of patients with Her2+ breast cancer. There have been some great advancement recently in more personalized cancer treatment such as with the design of Herceptin and I want to be a part of the discovery of new drug targets and the design of novel anticancer drugs. Researching novel ways to personalize medicines will combine my interests in the biology fostered in the genetic engineering lab and the chemical aspects of my research in the medicinal chemistry lab to contribute to improving the treatment of cancer.
Featured image: Instagram | Hanna Erickson (@MDPhDToBe)
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