Md Phd Essay

5. Write an awesome personal statement! (2 & 3 can continue to be repeated throughout the process)

MD-PhD Programs: The Ultimate Guide (2023)

Everything you need to know about MD-PhD programs and how to get in, including example MD-PhD essays and complete lists of MD-PhD and MSTP programs by state

(Note: We recommend using this resource alongside our free, 102-page comprehensive guide to medical school applications, Get Into Medical School: 6 Practical Lessons to Stand Out and Earn Your White Coat.)

Part 1: Introduction

Part 2: An overview of MD-PhD programs

Part 3: How to apply to MD-PhD programs

Part 4: How to write MD-PhD essays (examples included)

Appendix A: Complete list of Medical Scientist Training Program (MSTP) institutions

Appendix B: Complete list of MD-PhD programs

Part 1: Introduction

If your career goals include both practicing medicine and diving deep into scientific research, you may have your eye on MD-PhD programs. You might also wonder if applying to MD-PhD programs differs from the traditional medical school admissions process.

The two processes are distinct in several different ways. Yet, while the majority of medical schools offer these dual-degree programs, the differences between MD and MD-PhD admissions are neither widely discussed nor well understood, largely because far fewer students apply to become “physician scientists.” In the 2022–2023 admissions cycle, there were 55,188 MD applicants vs. just 1,793 MD-PhD applicants—nearly 30 times fewer.

Because the number of MD-PhD applicants is comparatively small, there’s also simply less information available to help prospective applicants through the MD-PhD admissions process. That’s why we created this guide, which will answer the many questions that we commonly receive about MD-PhD applications.

We’ll provide information to help you decide whether these programs are right for you, strategies you can use should you choose to apply, discussions of the required MD-PhD essays (including examples), and complete lists of MD-PhD and MSTP programs so you can maximize your odds of getting in.

Part 2: An overview of MD-PhD programs

What are MD-PhD programs?

MD-PhD programs are joint (i.e., dual-degree) programs that allow you to receive medical training and develop expertise in a research area. Most MD-PhD students complete dissertation research in biomedical sciences like biochemistry, genetics, and neuroscience, to name just a few examples. However, some may specialize in other fields, including anthropology, public health, bioengineering, and bioethics.

What are Medical Scientist Training Programs (MSTP)?

MSTP programs are a subset of 50 MD-PhD programs that are funded by the National Institute of Health (NIH). While MSTP admissions are very competitive, these programs come with many benefits including full tuition coverage, a living expenses stipend, and professional development opportunities such as seminars, conferences, and mentorship. The MSTP initiative is meant to encourage the development of physician scientists to advance the medical field through research.

Many non-MSTP programs, however, will also provide some of these benefits, such as tuition remission and living stipends. Each program’s resources and offerings will differ.

How many MD-PhD programs are there?

As of February 2023, there are 116 MD-PhD programs in the United States and 24 in Canada. You can find the full list of current programs at the end of this guide, as well as on the AAMC website.

How long are MD-PhD programs?

MD-PhD programs are designed to be completed in 7 to 8 years. A minority of students complete the program in 6 or 10 years.

Here’s what the typical MD-PhD curriculum looks like:

• Years 1–2 will be spent mostly on completing medical school coursework.
• Years 3–6 will consist mostly of PhD research.
• Years 7–8 will be spent mostly completing clinical rotations.

Following the completion of your MD-PhD program, the majority of MD-PhD grads go on to match into medical residencies and fellowships—this means another 3–7 years of training, depending on what field you enter. As you can see, earning an MD-PhD is a substantial time commitment.

What are the benefits of having MD-PhD attached to your name?

Physician scientists are uniquely equipped to investigate diseases because of their extensive scientific and medical training. This type of work has the potential to impact the lives of millions of patients. While MD physicians can also pursue meaningful research, they typically don’t receive specialized training unless they seek it out.

On the other hand, MD-PhD graduates develop the necessary research skills during their graduate studies to eventually pursue independent research projects, run their own labs, and so on.

Moreover, in some circles, MD-PhD graduates enjoy additional prestige because they’re seen as research experts simply by virtue of going through such a rigorous program.

What kind of residencies do MD-PhDs enter?

MD-PhD graduates have traditionally entered medical residencies in internal medicine, pediatrics, or pathology. While those are still the most common choices, the range of specialties chosen by MD-PhDs has widened. Other relatively popular specialties include psychiatry, general surgery, anesthesiology, neurological surgery, and neurology.

There are also a growing number of “research residency programs.” Specifically designed with physician scientists in mind, these programs integrate research into their clinical training, which often means that specialty training is shortened by a year.

No matter what residency you match into, MD-PhD grads are often considered desirable candidates for programs at top academic institutions due to their additional training.

What is the average MD-PhD salary and career?

The average physician scientist salary is currently $207,635. However, your salary will depend largely on whether you work in the public or private sector, and what medical specialty you choose.

One thing to keep in mind is that, although some programs are fully funded, MD-PhD programs take 3–4 years longer to complete than an MD program. Therefore, MD-PhD graduates will not begin earning a salary until several years after their MD counterparts.

Your typical career path as an MD-PhD graduate will be to become a faculty member in an academic medical center, such as a medical school or teaching hospital, where most of your time will be spent on research activities; other duties usually include teaching, administrative work, and clinical service. A large portion of your compensation will come in the form of research grants. Around 75% of MD-PhD grads follow this path.

Another sizable portion of physician scientists—around 16%—work as physicians in private practice.

These two career paths account for the vast majority of MD-PhD grads. Still, there are those who earn a comfortable living in the private sector working for pharmaceutical or biotech companies. Others work in governmental or nonprofit research organizations like the NIH and the Howard Hughes Medical Institute.

Part 3: How to apply to MD-PhD programs

How competitive are MD-PhD programs? Is it easier or harder to get into an MD-PhD vs. MD program?

The competitiveness of MD-PhD programs vs. MD programs depends on how you look at it.

• Comparing programs at the same school: At some highly competitive medical schools, less than 3% of applicants are admitted to the MD program, whereas about 10% of MD-PhD applicants get in due to a smaller applicant pool.
• Comparing overall acceptance rates: During the 2022–2023 application cycle, 709 out of 1,793 applicants (39.5%) matriculated into an MD-PhD program. This number is slightly lower than the overall admissions percentage to MD programs during the same cycle (41.2%).
• Comparing stats: In the most recent admissions cycle, the mean GPA and MCAT score for MD-PhD matriculants were 3.82 and 516.2. For MD matriculants, the mean GPA and MCAT score were 3.75 and 511.9.

Overall, it’s fair to state that MD-PhD admissions are more difficult than MD admissions. However, because MD-PhD programs so heavily emphasize your research track record, you may be more or less competitive for them depending on your stats and extracurricular profile.

Do MD-PhD programs require that I take the GRE in addition to the MCAT?

It depends on the specific medical school and PhD discipline you’re applying to conduct research in. Non-medical disciplines (e.g., sociology) are far more likely to ask for your GRE score in addition to your MCAT score. You should review application requirements months ahead of time to ensure you meet them.

How should I prepare differently to apply for MD-PhD programs?

The key differentiator between MD-PhD and MD programs is their research emphasis. If you’re considering applying to MD-PhD programs, make sure you will be able to demonstrate a longstanding commitment to research, preferably in one to three different labs. Moreover, aim to become an author on multiple publications to boost your admissions odds. Finally, make sure to develop strong rapport with your labs’ PIs so that you can secure strong recommendation letters when the time comes to apply.

With regard to coursework, the same ones that satisfy MD program requirements will satisfy MD-PhD programs’ requirements. In other words, you won’t need to take additional prerequisites to qualify for MD-PhD programs.

How many MD-PhD programs should I apply to?

It depends on several factors, including:

• Your stats and extracurricular background: The higher your stats and the stronger your extracurricular—especially research—background, the greater your overall odds.
• The competitiveness of your school list: The more selective the school, the lower your admissions odds there.
• The number of concurrent MD applications: The more schools you apply to overall, the greater your total admissions odds.

Can I apply to MD and MD-PhD programs at the same time?

Yes. Simply indicate on your AMCAS application application which schools you’d like to apply for as an MD candidate vs. an MD-PhD candidate. Most schools who reject you for their MD-PhD program will still consider you for their regular MD program.

What is the MD-PhD application timeline like?

It mimics the MD application timeline. Ideally, you’ll want to submit your primary application as soon as possible after AMCAS opens for submissions in late May/early June. You should then aim to pre-write your secondary essays so you can submit your supplemental applications within two weeks of receiving them, usually sometime in July. MD-PhD interviews typically take place between October and March, with most interview invitations sent out during that same period.

Do I face a disadvantage if I apply MD/PhD, get rejected, and essentially lose out on the early rolling admissions benefit?

In our experience, we have observed no such disadvantage. We have students who get into some MD/PhD programs, while others get deferred but are ultimately accepted into MD programs. Therefore, we encourage you to apply MD/PhD wherever you hope to attend such programs.

Part 4: How to write MD-PhD essays (examples included)

How does the MD-PhD application differ from the MD application?

You’ll have to submit two additional essays through AMCAS—on top of your personal statement and Work and Activities section—for MD-PhD consideration:

• The MD-PhD essay, which asks for your reasons for pursuing the dual-degree program
• The “significant research experience” essay, which asks for details about the scientific research you have conducted

Below, we’ll go over how to approach each MD-PhD essay, show you full-length examples, and discuss what makes them successful.

MD-PhD essay

In this essay, you’ll explain why you want to enter a dual-degree program. Your essay should thus focus on why you need to complete both an MD and a PhD, and why you wouldn’t be fulfilled by a career that didn’t include both research and clinical work.

To explain their reasons for applying, applicants sometimes write about how they love both research and medicine, and simply couldn’t decide which to focus on. A weakness of this approach is that these essays often end up describing research and medicine in isolation from each other, which highlights that the applicant hasn’t really thought through how they interact. This might inadvertently suggest to adcoms that you actually would be better off in a standalone MD or PhD program.

Instead of this, we suggest discussing how you can’t envision not having both in your life. In other words, focus on why the combination of research and medicine is important to you. How have you and how will you apply research to your clinical work and vice-versa? What does their integration offer you that a standalone program won’t? By showing how the two areas cross over and impact each other, you’ll be able to make the case that an MD-PhD program is right for you.

Here’s an example that discusses this successfully:

My clinical work and research during college seemed separate. As a longtime psychiatric emergency department (ED) volunteer, I worked firsthand with patients and families in medical and psychological crises. As a researcher, I initially organized patient files before creating and managing a new patient database for a project identifying risk factors for stroke and cerebrovascular disease in underserved and Latino populations. It wasn’t until my postgraduate years that I began to integrate my passion for mental health treatment with research.

After graduating from college, I accepted a research associate position in the Columbia University Department of Psychiatry, where I worked in Dr. Joan Stephenson’s autism assessment lab. I trained to reliably evaluate individuals suspected of having autism spectrum disorder (ASD) using behavioral observation and clinical interview methods to determine their eligibility for study participation. While my experiences in the Stephenson Lab were markedly different from working in the psychiatric ED, I realized that the importance of empathic care transcends the acuity of a patient’s condition. For instance, I distinctly remember a mother who feared that her 2-year-old son would receive an ASD diagnosis like his older brother, despite her and her husband praying for years that they would have one child with typical development before they were unable to have other children. When the lead psychologist confirmed their younger son’s ASD diagnosis, the mother broke down in tears. Before providing information on the boy’s prognosis and ASD treatment options, the psychologist and I spent the next 15 to 20 minutes validating the mother’s concerns. At that point, we figured the mother needed someone to tell her that her feelings were normal and that she wanted the best for her children. Doing so helped the mother be more receptive to our treatment recommendations.

My fascinations with mental health and cognitive psychology stem from believing that differences among human beings are not limited to the physical or social or mental aspects of development, but encompass their interaction. Reflecting on the challenges of living with Tourette Syndrome and coming from an immigrant family, I realize that the distinct combination of life events we experience, referred to simply as “environment,” is what truly makes each of us unique.

My life and research experiences have collectively taught me how conditions aren’t merely something you study in a lab out of curiosity, but rather how they dramatically impact patient life and outlook. Moreover, these experiences helped me realize my desire to become a physician scientist and pursue translational research to directly improves peoples’ lives on a larger scale.

Why does this essay work?

• This applicant does an excellent job of explaining how he came to realize that his passions for clinical work and psychiatric research, once separate, actually complement and benefit each other. For example, he discusses an experience in which empathy, which is typically thought of a trait of physicians rather than researchers, came into play while working as a research assistant.
• He also writes about how research doesn’t exist in isolation in a lab or purely for the pursuit of knowledge but, rather, has a real-life impact on people’s lives. By incorporating specific examples, including his own experiences of living with Tourette Syndrome, he convincingly makes the case that he has a firsthand understanding of the practical importance of research.
• The essay ends with the applicant’s goals for his career. In your own essay, you might go one step further than this applicant did by providing greater specificity—for instance, if you have a particular research interest you hope to pursue, mention it. That said, it’s not necessary to know yet exactly what problem or topic you hope to research so long as you can mention a broad field of interest, as this applicant did.

Significant research experience essay

Your significant research experience essay is where you’ll provide details about your notable research experiences. This includes:

• Durations of your research experiences
• Your mentors’ names and affiliations
• What you investigated
• Your project contributions

In writing about their research projects, applicants are sometimes unsure of how technical or detailed their descriptions should be. You don’t want to include so much jargon that your essay reads like a scientific manuscript submission, but it’s okay to include technical details so long as they’re at a level that any scientist will be able to understand.

While describing your experience is your main goal in this essay, you might also take on the secondary goal of communicating what kind of student and researcher you’ll be. Remember that adcoms are looking for candidates who will be able to handle the strenuous challenges of an MD-PhD program. So, this essay can also be a space to convey personal qualities like resolve, problem-solving, initiative, leadership, and the ability to absorb lessons and grow.

Here are a few different ways that you can incorporate personal qualities into your significant research essay:

• Write about what you learned from specific research experiences and how you’ll apply those lessons going forward.
• Describe not only your successes, but also your failures and what they taught you.
• If you played a leadership role in some of your research experiences, make sure to highlight that you weren’t simply taking directions from someone else.

Let’s take a look at an example:

I have had X significant research experiences:

1. Professor Sean Guo, MD/PhD, Columbia University Department of Psychiatry, March 2016 – August 2018

The Guo Lab investigates the development of child psychiatric conditions through imaging genetics. My project focuses on conducting cross-modal imaging genetics analyses between genes in the catecholamine system, including ADRA2A, 5-HTTLPR, DAT1, and DRD4, and functional and connectivity imaging data to unravel the genetic bases of neural networks underlying response inhibition (RI) in children. Alongside Dr. Guo, I found that youth with greater levels of impulsivity and inattentiveness, based on standardized behavioral rating scales, displayed greater latency on a computerized RI task. Moreover, impulsive and inattentive traits, as well as performance on the RI task, was negatively associated with functional anisotropy (FA) and functional coupling between the presupplementary motor area (preSMA), interior frontal cortex (IFC),and subthalamic nucleus. Atypical connectivity and functional coupling among these brain areas were observed to be fixed and nonprogressive regardless of age. Furthermore, we found a positive association between the blood-oxygen-level-dependent signal (BOLD) and FA in the preSMA, right IFC, STN, and occipital lobe.

Identifying genetic effects on neural function and connectivity related to RI have helped us begin elucidating neural pathways of inhibitory control. This project is translational by virtue of its integration of previously unexplored genotypes and behavioral data with functional and white matter connectivity. Our next step is to apply these early causal models of RI to develop targeted interventions. This is particularly relevant given that RI deficits are associated with numerous conditions of clinical, public health, and economic significance, including substance disorders, addiction, and obesity.

I co-authored these findings in two manuscripts published in [Journal] and [Journal]. I also co-designed and presented a poster at the [Year, Conference]. Moreover, my colleagues and I plan to submit a paper to [Journal] in the coming weeks. If accepted, this would be my third first-authored publication.

Through this project, I learned a number of neuroimaging research techniques, including recruiting, consenting, and imagine study participants, processing functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data, conducting statistical analyses, and writing manuscripts for peer-reviewed journals. It was extremely gratifying not only to learn these new skills, but also to take greater ownership over a project than I have in the past. This experience helped me to better understand what goes into a study from start to finish and has prepared me for future leadership.

(Note: The applicant goes on to include additional significant research experience entries using the format above.)

Let’s analyze what’s working in this essay:

• The applicant provides provides all the relevant details about a specific research experience. Note that it’s not always necessary to go into this level of detail—given that you can use up to 10,000 characters, how much detail to include will often depend on how many significant research experiences you want to convey. This excerpt uses about 2,800 characters, meaning that the applicant has room to add 2–3 more experiences at this level of detail.
• He uses an entry format, which is a great strategy to provide clarity and structure to your essay. If you wish, you can also discuss your experiences in narrative form.
• He concludes the entry by talking about what he learned both in terms of specific skills but also in terms of lessons that he will apply to future work. This helps adcoms get a glimpse of the human behind the accomplishments.

Final thoughts

For the aspiring physician scientist, MD-PhD programs will provide the training you need to integrate research and clinical work. The MD-PhD admissions process is challenging and differs from that of traditional medical school admissions. In addition to completing medical school prerequisites and earning excellent grades and MCAT scores, you’ll want to ensure that your research experience is robust going into application season. Then, plan to devote significant time to your required application materials, including the two MD-PhD supplementary essays, in order to have the very best chances of acceptance.

Tag: Personal Statement

Writing your personal statement? Here’s what you need to do:

3. Reflect on how the information you read may help you write your statement

4. Repeat 2 & 3 until truly inspired to write

5. Write an awesome personal statement! (2 & 3 can continue to be repeated throughout the process)

AMCAS M.D. Personal Statement

When applying to medical school, whether you’re applying to MD or MD/PhD, you will have to write a personal statement regarding your reasons for pursuing a career in medicine. This statement, with a limit of 5,300 characters, is a great opportunity to let your passion shine through and complement your GPA, MCAT score, and extracurriculars to convince admission committees that you would be an excellent addition to their program. As an example, here’s my MD personal statement:

Lying beneath the linear accelerator, I put myself in a patient’s position. I was eager to understand what it felt like to have cancer, to familiarize myself with the fear, worry, and pain of the life-threatening disease and its dangerous treatment. As I looked up at the machine, I wondered what it would feel like to have radiation directed at my body. Did it hurt? Did it not? Despite these insecurities, I was reassured, had I been a patient, that I would have the doctors’ undivided attention and vast medical knowledge helping me through the therapy. I had seen these doctors in action earlier when I looked in on a patient being prepped for this treatment, and I admired the bond that the doctors had formed with the patient based on trust and understanding to ensure them that they are in good hands. It is experiences like this one in radiation oncology that continue to attract me to becoming a physician.

As a girl who knew little of medical science at the time, I was nonetheless captivated by the complexity of medicine and aspired to be more involved in the healthcare community. I became a volunteer and immersed myself in various areas around the hospital, learning to appreciate all of the workers who make both a direct and indirect impact on patients’ lives. As a volunteer, my favorite phrase to tell patients has been “if you need anything, just let me know.” I pride myself in being able to ensure them that I will do everything I can to help meet their needs though it was not until I met a 97-year-old patient in a nursing unit that I realized the full depth of that phrase. Alone and recovering from surgery, he needed someone to talk to more than anything, and his face lit up as I told him that I would be happy to sit with him. While we talked, I learned that his wife had recently died, that they never had children because they could not afford it, and that he was restricted to living the rest of his life between the nursing home and the hospital. Empathizing with his struggles and his loneliness, I helped him feel connected to another person to reduce these emotional pains. I then understood that the phrase could provide even more comfort to a patient than the physical relief I had initially intended.

Ambitiously, I desire to further serve patients’ needs by using my interest in research to complement my work in the clinic. Being a scientifically curious and innovative individual, I am optimistic about the opportunities for the advancement of knowledge regarding the chemical, biological, and physiological interactions that comprise human life, and I want to be on the cutting edge of such discovery. I have already begun to be involved in such medically relevant research in medicinal chemistry so that I can study how carcinogens chemically react with biological molecules to have a mutagenic effect. As an interdisciplinary scientist, I have learned to combine multiple angles on a situation such as that of a chemist and a biologist to more completely understand it, which can help me translate scientific information to clinically relevant techniques. This is also an ability I hope to emulate as a doctor to recognize and address the intricacies of medical ailments from their scientific basis and systemic effects to their psychological and social impacts on the lives of patients and their families.

As I have explored careers in medicine, pharmacy, and science, I have become passionate about cancer, and I want to combine my intellectual interest, ambition, and compassion to do everything that I can for patients as an oncologist. Other than its challenging conceptual complexity and opportunity for expansion, I am attracted to this specialty because of the longevity of the disease’s effects that enable formation of strong doctor-patient relationships as I have seen in my volunteer work in an oncology intravenous infusion suite. My most touching observation was when I helped a woman on her last day of a round of chemotherapy by taking her picture with various nurses and doctors that were a major part of her treatment. I admire that these medical professionals have made such an influence on her life that she wants to commemorate it in photographic memory. As she left, she did not say goodbye but instead said see you next time; it is determined patients like her who inspire me to be more involved in oncology and its research to see that I do everything that I can to help them win their fight against cancer. Although I desire the lasting connection to patients, I would much rather see them healthy than having to return for multiple rounds of treatment.

Valuing knowledge, I have placed myself in positions to try to better empathize with patients’ experiences and to appreciate the role of doctors and other medical professionals in their care. Through such learning experiences, I have become passionate about understanding and treating cancer, and I am determined to be more involved in the complex health care system by bridging the gap between science and medicine to best serve those afflicted with the disease. I take pride in my ability as an interdisciplinary scientist and I believe that I can use that skill to complement my work as an oncologist so that I can combat cancer as a true physician-scientist.

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AMCAS M.D./Ph.D. 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 MD/PhD statement has a 3,600 character limit and serves to strengthen your argument why you want to do both MD and PhD. As an example, here is my MD/PhD personal statement:

As an undergraduate, I have begun to experience the complementarity of medicine and scientific research. I now understand that clinical work as a physician requires not only application of the scientific principles learned throughout college and medical school, but also requires compassion and an interest in the personal side of health care. For me, this interest was reignited by my experience in research where I learned more about the effects of cancer and had first hand experience in the search for a better understanding of the disease. From learning about the devastating effects of the disease and the efforts that doctors and researchers are putting forth to improve treatment of it, I was inspired to resume volunteering at the hospital, doing anything I could to be more involved.

My research inspires me to pursue medicine, and now, my experience in the hospital motivates my efforts in the lab. In my current research, I have found that at first, I easily became discouraged when, after seven months of trying multiple methods for synthesizing a single molecule, another attempt fails. Before I began to volunteer in the intravenous infusion suite, I reacted to such difficulties with near resentment of my work, at times, and continued to try just to reach the end goal set for me. Now that I have returned to the clinic as a volunteer, I have found new motivation in some of my more straining times in the lab. At the end of a long workweek, while infusing my sample only to find that the product degraded or was not formed at all, I remember my morning in the clinic and the patients that I met. I regain my optimism and drive much faster, as I remember that I am not only doing this for myself or for the scientific knowledge, but for them.

Through my learning experiences in the lab and the clinic, I have become passionate about cancer and want the next eight years to prepare me for spending the rest of my life devoted to doing as much as I can to help improve the lives of those affected. Clinical and lab work now seem to be individually inadequate options for my ambition. Rather, with the training of an MD/PhD program, I hope to bridge the gap between these two areas of interest to become an academic oncologist to more broadly contribute to the fight against cancer. I look forward to making discoveries in the lab and being able to apply them in the clinic. I also want to amplify my training and experience to help teach a new generation of doctors and researchers to not only be able to excel at their own areas of focus, but to gain an understanding of a broader range of experiences and ways of thought. I believe in the ability to utilize the complementarity of these roles to maintain my motivation and compassion, to contribute novel and useful knowledge, to influence future generations, and to ultimately make the greatest impact toward making the lives of patients and their families better.

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)