My third and final rotation

To put it simply, my third rotation was different.

Leaning toward joining my second rotation lab, I picked my third rotation advisor not because of the research focus but because the PI (primary investigator) was a new and enthusiastic professor. Seriously, this PI is one of the most passionate people I have met within the field of science. I had met them on my interview weekend and really enjoyed hearing their take on academia as a recent post doc. As they told me about their research I kept asking “You could apply that to cancer, right?” and they would say, “Yeah, but we’re doing it with muscular dystrophy in the heart” or “Yeah, but we’re looking at the liver.” The scientific area they looked at in the lab (RNA expression/splicing) was a secondary reason why I chose the lab for my last rotation.

I knew I didn’t want to look at the liver or the heart, but I thought I’d try just to see if it sparked my interest outside of cancer in general.

I solidified my decision for doing my third rotation in the lab before I began the second. Then as I began my second rotation, an opportunity to form a collaboration for a grant related to cancer arose and I suggested my third rotation advisor as a collaborator since the techniques used in that lab could be applied to our research. We together wrote our letter of intent for the grant and I began planning a project for me to do during my rotation.

Unlike most students who begin their rotations and are introduced to the lab’s work then given a project, I came in to the rotation declaring my project and was given a side project to get used to the techniques of the lab before applying them to my precious samples. I was given some papers related to the liver work that I was doing but other than my introduction, I never really had a conversation about what I could do with it as a thesis project. I found out at the end that they had that kind of discussion with other rotation students but because I was so set in my ways that there was no need to convince me to switch my interests from cancer and the immune system to the liver.

While I ended up not joining the lab, I had a great time getting to know everyone in the lab (though it was relatively new, there were a lot of undergrads to get to know in addition to the grad student and post doc). I will definitely miss them but I hope to continue to the collaborative project with the lab so I will still get to interact with them. Nonetheless, this rotation re-introduced me to techniques I hadn’t used for many years such as western blots (which I had done in biochemistry lab) and PCR (which I had done in my first undergrad research lab), which was nice to go back to (and made me sort of nostalgic about my first undergrad lab)! So overall, it was quite enjoyable.

I ultimately ended up joining my second rotation lab, but I am glad that I complemented the first chemistry-focused lab developing chemotherapeutic agents and the second immunology lab focused on developing immunotherapies for brain cancer with a lab focused on understanding the RNA expression and splicing changes in disease and development. I ultimately joined the immunology lab, but as I’m researching potential directions to go with my project, I am finding ways to include the three distinct labs in which I did my rotations.

Unlike many students who came in to the program knowing that they wanted to work in a particular area – be it microbiology or biochemistry – or a particular topic – such as non-coding RNA – I came in with a general purpose to have my work relate to cancer therapy. I rotated in both biochemistry and physiology labs that were in quite distinct areas of chemical synthesis and characterization of potential drugs, immunology, and RNA expression. My list of potential research advisors included PIs from all four departments in my specific graduate school. And I went to seminars for all departments as I found some related to my interests in every department.

While I may have a different way of deciding my thesis lab, being much more of a generalist, I think in the long run, it’ll do me well. It’ll help me be a more well-rounded researcher with a broader scope of the implications of my work and the methods available. It’ll also keep things exciting. Instead of being a specialist in a certain scientific level be it biochemistry, microbiology, physiology, etc., I hope to be a specialist in a disease. Pathology is so complex that I feel this is a good perspective to have for my ultimate goal. Throughout the fall, I have made great connections with professors and graduate students during my rotations from many different areas who I can go to for help throughout my journey, and I can’t wait to get started in my permanent lab!

Reflections from my second lab rotation

Each August, my MD/PhD program holds a retreat that includes inviting alumni back to speak to the current students. This year, the theme of one of the alumni’s talks was “serendipity.” Defined as a happy accident, serendipity was a great way for her to describe how she came to her current career as opportunities arose that were best for her but did not fit a conventional career path in medicine. This same term applies to much of my path. It was serendipitous for me to even find out about MD/PhD programs – discovering they existed while looking at grad programs just days before taking the GRE – and apply to my specific school – being encouraged by an e-mail to apply – and it has turned out to be the perfect program for me. And so, I’ve learned to embrace of such pleasant surprises by keeping myself open to change as best I can to see where life will take me.

Today marks the three-month mark of me living in Illinois. It’s crazy to realize that a quarter of a year ago I was making the move excited to start my new life in a new state as an MD/PhD student. Now, it feels like home. In that time, I’ve made many new friends who are grad students like myself, I’ve learned to live on my own, and I’ve adjusted to the responsibilities of being a graduate student. It has been a major change from my comfortable undergrad life in Minnesota where I had family nearby, roommates, and plenty of extracurricular activities to keep me preoccupied.

As I’ve gone through my lab rotations, my research interests have also shifted in a somewhat serendipitous manner. In undergrad, I imagined my research to contribute to improving chemotherapy by developing more targeted small molecules as potential drugs. I rotated first in the one lab that was related to this and that I was interested in before coming to here, and it turned out to not be all of what I wanted in a lab. Fortunately, I found a lab that had not been listed as taking graduate students in the spring when I visited for my interview but was related to cancer therapy – immunotherapy for brain tumors, specifically – and so I took a chance and contacted the PI. It turned out that they were going to be taking rotation students, so I met with them before the school year began and we hit it off! They were actually going to a neuro-oncology symposium at Minnesota, my beloved alma mater, at the end of the first rotation and wanted to have me come with but I had already set up my first rotation so we agreed that I would do my second rotation in the lab and not go to the symposium.

When I met with the PI again near the end of the first rotation, we confirmed that we were going to do whatever we could to be matched in the process of assigning labs. I was going to list the lab as my top choice and they were also going to request me as a student. The next day, we also figured out a way to get me to the symposium in Minnesota by asking my first rotation advisor if it would be alright if I took the last couple days of my rotation to go. They agreed and so I left on the Wednesday night before the symposium and drove 4 hours to Madison where I stayed with one of my best friends who just started a PhD program there. I left the next morning at 4:45 am and made it to Minnesota at 9, just a little late to the symposium but better rested than if I had woken up early enough to be on time for the 7:30 symposium registration.

Being able to go to this symposium was possibly the best opportunity that I’ve had so far in grad school. I learned a lot about neuro-oncology and met many big names in the field. Most importantly, it inspired me as there is a cohort of researchers at Minnesota ranging from basic research to animal and human clinical research devoted to developing immunotherapies for brain tumors who all spoke at the symposium. My knowledge of immunology – and immunotherapy specifically – was limited since I had only superficially been exposed to the topic in my physiology and health psychology classes in undergrad, but I left that symposium really believing that triggering the immune system to attack cancer cells had the potential to be a much more effective mode of therapy than the slash, burn, and poison techniques that are currently used (surgery, radiation, and chemotherapy). It was also a great opportunity because it was homecoming so I was able to stay for the weekend, see many of my good friends, and go to the homecoming festivities for the first time as an alumna.

With my former roommate at the homecoming football game!
With my former roommate at the homecoming football game!

As I said in my previous post, “The first rotation is the hardest,” the structure of a lab rotation can vary drastically depending on the lab. While my first lab had me working on a project of my own, my second lab had me essentially just observing. This lab is small with just a graduate student, three undergraduate students, and the PI, so there was less experimental work to observe. This gave me free time during the 5 weeks to research the literature and gain a more in depth understanding of immunotherapy and begin to formulate ideas of my own to pursue.

While there was less lab work to observe, when there was something to observe it was something I had never seen before. As a chemistry major working in a medicinal chemistry lab in undergrad, my work primarily involved analytical chemistry with a little bit of tissue culture. On the other hand, this lab primarily does work with mice and so the first time I had ever worked with mice I ended up doing a little brain surgery to inject cancer cells into their brains, which they were going to live with for a week when we would collect some of their organs for immunohistochemistry. I had never been a fan of dissections (topic of a future post), but I actually enjoyed doing surgeries on mice.

So you may be wondering what interests me so much about the immune system. Well, the immune system is the body’s defense against foreign antigens and so it can be activated to attack bacteria, etc. that are recognized as non-self. Human cells can also be recognized as non-self and can be attacked such as when a person receives an organ donation from a non-compatible donor and the body rejects the organ. To control the immune system and prevent it from attacking the body’s own cells, there are also immune cells that suppress the immune response toward an antigen. Since cancer cells arise from an endogenous (self) cell, they can be missed by the immune system even though they have altered expression of proteins that could distinguish them from normal healthy cells. Additionally, cancers tend to emit signals that promote immune suppression and thus prevent their destruction. I’m hopeful that better understanding this cancer-induced immunosuppression and finding a way of inhibiting it will be able to improve immunotherapies.

You may also be wondering what interests me about brain tumors. Well, one in four cancers that spread throughout the body ends up metastasizing to the brain (about 170,000 will be diagnosed in a year) and the prognosis for these patients is generally poor. For those diagnosed with brain metastases, their life expectancy is usually less than 2 years. Brain cancers are also more difficult to treat because the blood-brain barrier is limiting for delivery of therapies. Therefore, there is an extra challenge in developing therapies, and I am always up for a challenge. 😉 This can be overcome by surgery, which is non-ideal to repeat because it exposes the brain, increases the likelihood of infection, and may not completely remove all cancer cells. As an alternative, immune cells can cross the blood-brain barrier easily, which makes immunotherapy a viable option for treating these tumors.

Though I didn’t need to have a project of my own during my rotation, I was itching to have something to sort of call my own. I finally got my own project started at the end of the rotation that I’m continuing to my third and last rotation in a lab that looks at alterations in RNA splicing during development. I plan to use the RNA analytical techniques of that lab on samples from my second lab. In fact, soon after I began my second rotation, I established a collaboration between the two labs! Therefore whichever one I join, I can work with both PIs because I like both of them as well as their labs.

Just 29 days until I can officially join a lab. Until then, I will need to decide which of these two labs I will be the best for me. Regardless, I should be able to do the science that I want to do, so now it’s just picking my primary lab and advisor.

The first rotation is the hardest

They say your first lab rotation in graduate school is the hardest – you’re adjusting from undergraduate to graduate student, you’re adjusting to potentially a new school and a new state, you’re adjusting to new people, and you’re adjusting to new research and a new lab. Nonetheless, this is a universal experience: every graduate student in the program before you and all of your peers have gone through the same thing or are currently going through it with you. Depending on the lab that you’re assigned, this experience may slightly vary. Some labs will have you work nearly independently; others will have you follow around a graduate student in the lab.

Though it may be difficult, it is also one of the best times of graduate school because there is less pressure on your productivity while you work on research that is likely not related to your future thesis as you may not even chose that lab as your thesis lab. The emphasis of this time is much more to get to know the lab, the professor, the area of research, and figure out if this is a place that you would like to spend the next five or so years of your life working. If you’ve read my previous post “Picking a thesis lab is a lot like dating,” you hopefully understand how picking a thesis lab pulls at your emotions just like dating. Let’s just say my first rotation came with a rollercoaster of emotions.

From the time that I first looked into research at this school, there was one lab that stood out from the rest in appealing to my research interests. I read some of the recent work of the lab and met with one of the graduate students during my interview weekend since the PI (primary investigator, or professor) was out of town. Over the summer, I looked more into their papers and sent an e-mail to the PI to introduce myself as an incoming MD/PhD student, give a background on my research experience, and explain how the lab’s research fits with my research interests. I asked if they would be willing and able to take a rotation student from my program this fall and if they’d like to meet once I moved to campus.

The PI agreed on meeting and so soon after I made my move, we met to discuss the potential of me rotating in the lab. There was some concern regarding my position as an MD/PhD student because of previous experiences with MD/PhD students trying to rush through their PhD to get to their clinical years. I reassured them that I was there to get a full PhD, that on the spectrum of PhD to MD, I was much more on the PhD side having planned to go that route alone for most of undergrad. Nonetheless, I was warned that PhDs tend to take a little longer in the lab though the publications are often stronger than others. This time frame is perceived to be detracting to MD/PhD students as our education is already so long.

As one goal of the lab is to identify small molecules that have an anticancer effect, my desire to become an oncologist seemed to appeal to the PI. We felt that the first rotation would be best for me to be in the lab since during the second, they’d be getting chemistry students joining the lab (these students don’t rotate, they just have to get to know PIs by going to lab meetings and whatnot then officially join a lab at the end of October). Our rotation assignments are ultimately decided by a committee to best fit everyone’s interests, so the PI helped make sure that we were matched by requesting me as a student in addition to me listing the lab as my first choice.

The lab assignments were released and we were matched! Before I had received my official assignment from our program, the PI had already found out and contacted me late on that Friday afternoon. Within 20 minutes of receiving their e-mail, I was at their office to discuss what I would be doing during my rotation and I spent the weekend reading papers to prepare. I was very excited to get started in the lab!

My assignment began that Monday and I started it by going to 8 am lab meeting before my 8:30 class. I briefly talked to the 5th year graduate student who was supposed to be my mentor and the PI introduced me to the lab. Being that it is a large lab, I didn’t really get to know many other students’ names but at least they got mine.

Following class, I met up with the graduate student and began my safety training. Most of the lab was in one building but three of us were in another a few blocks away so I didn’t really get a chance to meet many others in the lab. There was an older MD/PhD student in the lab who I had talked with over the weekend at our retreat who warned me that social cliques were strong in the lab, so I had to be extra careful to be on everyone’s good side. I was also warned that there was a hint of dislike toward MD/PhD students or at least biochemistry students as everyone but the one MD/PhD student were chemistry grad students. Being separated from most of the lab made it difficult for me to get to know others and work on getting on their good side.

At my first subgroup meeting on the second day of my rotation, I met with my PI, a collaborating vet, my mentor grad student, a post doc, and another grad student who were all working on a similar research topic. There we learned that the post doc had got a new job and would be leaving in the next month. To help with his work, my rotation project was then changed to complement his work in which he synthesized potential prodrugs – so much for spending my weekend reading papers to prepare for my rotation.

This shift in my rotation project took me away from biology to a much more analytical chemistry perspective. In fact, it was similar to my research in undergrad. My mentor graduate student gave me some papers to read about the topic and after that I went to the post doc mostly for help instead of the graduate student. I was okay with this because I was having a difficult time getting to know the student and I was becoming frustrated with having a mentor who did not seem too happy about having to help me. I know that its very important to know and get along with your fellow students but you just get to a point where it’s hard to continue to try. In fact, that was one of the most challenging parts of my rotation. They were a 5th year student and had their thesis to focus on so it’s understandable that they were less receptive to helping a new student who wouldn’t be helping progress their thesis, but it still didn’t make my experience better.

Though it was a large lab, I was incredibly surprised by the amount of attention I received from the PI. I was frequently given papers that they thought were interesting and would be valuable for me to read, and then we would meet and discuss them to make sure I understood their value and talk about how they applied to our ultimate goal. It was through this that I was led in the direction of a possible area of work for my thesis and so by the end of my rotation, I knew what would best benefit the lab and myself as a potential research project. I liked the way this was done so that I wasn’t just told “this is what I would want you to do” but more that I was directed toward that area of research, ultimately coming to it from my own experience in reading papers. I had many friends who did not have much interaction with their PI during their rotation, so I felt fortunate to be able to speak with mine regularly.

As I said, my rotation came with a rollercoaster of emotions. Some of the high points were actually getting assigned to the lab which was of high interest by many students, successfully optimizing an HPLC method for my analysis, and impressing the PI by not only reading the papers they gave me to read but finding others and bringing up what I read in those when we discussed the papers. Nonetheless, with the highs came the lows. As I previously mentioned, I was frustrated with not getting to know many students and having the ones who were supposed to mentor me not being too receptive. In time, I was able to meet more students and had some invite me to lunch but the set-up of the lab made it difficult as it was many small rooms instead of a big open lab so everyone was separated. Another low point was hearing from another MD/PhD first year who was interested in the lab that the PI had told them that they decided their lab didn’t fit with our MD/PhD program. After talking to other people in the group, I was reassured that they wouldn’t be showing interest in me if they thought that being MD/PhD actually would be detrimental my success in their lab.

Ultimately, I left the lab after my five-week rotation with a good impression. I could see myself being highly successful in the lab, so now the real dilemma comes from deciding whether I could be more successful in this lab or one of the other two that I will be rotating in. I told the PI I would be in touch in the following weeks as I begin to experience a new lab because my interest in joining the lab may affect how many new chemistry grad students they take. Whether or not I decide that a large lab full of chemists is the best place for me, I do really like this PI and this research, and I would love to form a collaboration if I choose a different lab so that we can still work together. 🙂

Getting research experience as an undergraduate/post-bacc student

Research is essential to advance our knowledge of the human body and to develop improved ways of treating diseases. Without the innovation of researchers, we still may be doing things like putting leeches on people to heal them of their illnesses or cutting holes in people’s heads to release “evil spirits” that were believed to be the cause of their ailments. To show your devotion to the medical field as a premed, you can get involved in research so that you can get a better understanding of how it is done and a better appreciation of the hard work that goes into the knowledge doctors use to diagnose and treat their patients.

So how do you actually go about getting involved in a research laboratory? If you go to a large research university like I did, it’s a little easier. You find professors that you’d be interested in working with from the university’s website and contact them asking if they’d be interested in taking on an undergraduate student. Your advisor will also be a good resource to contact for help with this. Expect to at least start off volunteering as putting money into an inexperienced undergraduate isn’t the most logical for someone working hard to maintain grants to fund their lab. Depending on the professor (also called the PI or primary investigator of the lab) they may ask you to take a directed research course to verify that you’ll spend enough time in the lab or they’ll at least expect you to be in the lab for a certain amount of time each week. Often, you’ll be paired with a graduate student or postdoctoral student who will be your mentor. You may just assist the student or once you’re more experienced you will get your own project that they will simply advise you about. If you don’t go to a large research university, you can still contact professors at your nearest university to see if they would be able to take you in their lab.

Also, keep your eyes and ears peeled for professors saying that they are looking for undergraduates for their labs. This is how I managed to land both of my research positions in undergrad. I found out about the first lab I worked in because the professor was a guest lecturer in my freshman genetics course. He began his presentation with talking about the importance of research for undergraduates and said that if any of us wanted experience, his lab was always willing to take more undergraduates. I emailed him the next day and he told me to come in and talk to his lab manager whenever I was ready to start work. I found out about the second lab I worked in from an email the professor had forwarded to the chemistry majors by our advisor that said she was looking for undergraduates. As this lab was in a more convenient location and was much closer to what I wanted to do, I jumped on the opportunity. Nonetheless, if you pick a lab this way, you may not be working on something that you would want to go into (like for me, genetic engineering of livestock, which I helped with in the first lab).

Another option is to apply for a Research Experiences for Undergraduates program, REU for short. These are summer research programs that let you to go to another school for 10 or so weeks to get full time research experience. The best part is that you get paid for it! To find more about these, search for “Research Experiences for Undergraduates” on your favorite university’s website or simply google it to find schools that are offering such programs. They are  highly prestigious programs that are highly competitive, so it is suggested that you apply to quite a few of them!

If you’ve graduated from college, there are still opportunities to get research experience without pursuing an advanced degree. One incredible opportunity that I wish I had known about before I applied to med school is the Post-baccalaureate Intramural Research Training Award (IRTA) offered by the NIH. This program is for college graduates who received their bachelor’s degrees less than two years prior to the date they begin the program who intend to apply to graduate or professional school during their tenure in the program. Essentially, the program consists of working in a primary investigator’s lab at one of the National Institutes of Health facilities. It has rolling admissions with just 10% or so admission rate, but it is a fabulous opportunity to try for! I applied in the late early spring of my senior year in case I didn’t get into medical school and had a PI contact me about working in his lab just a few weeks later. Unfortunately (or fortunately), I had been accepted to an MD/PhD program at that point, so such a backup plan was not needed. There’s a general application on the site, but it will help to contact PIs that you’re interested in working with to help you get into the program!

Surely there’s other places to get research experience such as individual study or at a hospital. When in doubt, your advisor is your best friend and can surely help you land a great research experience!


Featured image: Hanna Erickson

When I Synthesize My Molecule

When I synthesize my standard molecule in a reaction consisting of a drug, guanine, and cysteine for biological analysis in my lab, I see it not just as organic chemistry but also as a reaction in the body. It is a simplified biological system. The cysteine is part of a large protein and the DNA is part of an even larger chromosome. The drug has already been infused into the blood stream, distributed throughout the body while associating and dissociating with various biomolecules, absorbed into the cells, and has now entered the nucleus of a cancer cell. When the reaction occurs inside the cell as it is occurring on my lab bench, it will create a lesion to the DNA so bulky that it could stop DNA replication requiring either repair or apoptosis of the cell (ideally) thus killing the cancer cell.

It is so much more than understanding organic chemistry and performing a chemical reaction. It is looking at a specific part of that drug’s effect on the body and seeking to understand it on a molecular level. Yes, the drug is effective at treating certain cancers, but it is also useful to know why the drug is so capable. If we look to further understanding the chemical interactions that occur, perhaps we can be able to design future generation drugs from this drug to improve the efficacy and specificity of treatment to better eradicate cancer.

But we wouldn’t understand it if we didn’t have chemistry.

AMCAS Research Personal Statement

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)