Guest Post: PhD life – chasing the highs

The purpose of this blog is to share personal accounts of MD/PhD training, and I’m excited to expand the perspectives presented here with the first ever guest post! This post is by Alex Yang, who I first connected with via Twitter a few years back (and is a fellow liver lover!)


PhD life – chasing the highs

Alex Yang

Disheveled. Exasperated. Desperate. I had failed to co-immunoprecipitate my two proteins of interest again. I had lost track how many times I’ve tried in the first two years of my PhD. For those of you that aren’t in basic science research, the amount of failure is immense. I would estimate 90% of all experiments are failures. A co-immunoprecipitation involves pulling down with an antibody for one protein and blotting for another protein to suggest a protein-protein interaction. Theoretically if the antibodies are working, the technique shouldn’t be hard. But I couldn’t get it work. And I didn’t think I could ever get it work. I started questioning why I even attempted a PhD and didn’t just be a “normal” doctor like all my other classmates. Before I go on, let’s go back to see how I decided to be a #doubledoc in the first place.

Everything that I’ve accomplished and will accomplish, I owe to my first-generation immigrant parents. My dad is a PhD, professor in Immunology and Microbiology. Smartest person I know to this day. My mom is a MD, family doctor with a very large successful clinic. Hardest working person I know to this day. This naturally made me interested in pursuing a MD/PhD as I am a combination of my parents both biologically and degree-wise. Science was always my favorite subject in school. I remember starting to learn basic lab techniques in middle school and continued in high school. When I found a MD/PhD mentor as an undergraduate that beautifully combined both degrees and encouraged me to do the same, the rest was history. I applied MD/PhD right out of college knowing the long road ahead. First two years of medical school flew by, and now I was in a basic science lab studying genetic mechanisms of non-alcoholic fatty liver disease (NAFLD).

Back to the co-immunoprecipitation. Although medical school was challenging it did not prepare me for the failure of graduate school. In medical school, I had passed all my exams by a large margin. Failing was never an option, but it’s almost a daily occurrence in graduate school. As much as I failed the co-immunoprecipitation, I knew I couldn’t give up. Although I had evidence in over-expression models in cell lines, we needed evidence with endogenous proteins in-vivo specifically in a mice model. I was discouraged, but the post-doc that I worked with suggested we need to purify the lipid droplets from the liver in order to concentrate the proteins. That would give us the best chance to successfully immunoprecipitate both proteins. It was an extra step (actually more like 20), but it was a new direction to try.

I knew the chances of success was slim, but that’s what we do as graduate students. We have to learn from our failures. Optimize. Repeat. And finally, we persevere. I grudgingly purified the lipid droplets and added the antibody. The next day I blotted. When I exposed the gel, a single beautiful band appeared showing my band indicating my protein of interest. Who knew one band (no not the Jonas Brothers type of band) could give so much joy? I was ecstatic and relieved. When my principle investigator saw the results, he could only smile. Knowing I just accomplished something that no one in the world has ever done thrilled me. For those undergraduates reading this and still trying to decide if graduate school is right for them, I implore you to re-evaluate your experience in lab. Are the highs of the 10% of success high enough to carry you through the 90% of failures? If not, maybe consider just a MD as a PhD is all about persevering through failure. As for me, I was on cloud nine. The pains of the failures were wiped away by the joy of success. I didn’t choose the PhD life. It had chosen me.


IMG_1397About Alex: I’m a 4th year MD/PhD student at Wayne State University studying genetic mechanisms of fatty liver disease. In my spare time I like to cook, exercise, play video games, and write. Check me out on twitter @MDPhDinProgress.

Time Balance as a MD/PhD Student

Q (from ask.fm): As a MD/PhD student, do you have any time for yourself? For family and friends? To just take a break? I would like to do a MD/PhD program, but I want to enjoy my 20s…

A: Of course you have time! I fully want to enjoy my 20’s as well so even if I don’t feel like I have time, I MAKE time to enjoy it. When you’re in the graduate portion of your PhD, your free time is really based on how much your PI will push you (or how much you push yourself). It is an important consideration when you pick a lab. If the PI is understanding and aware that people are not robots who just work 24 hours a day to produce data, then you should be granted the time that you need. In fact, I’ve had PI’s tell me to go home because I’m in lab too late or I’m there on a weekend!

I actually just read a blog post today about this culture of pushing scientists too far (in response to a sad situation), and a particular quote from it stood out to me:

“The best (and more importantly, happiest) scientists I know are people who are interested in many things, who approach all aspects of their lives with engagement, purpose and openness.”

There seems to be a cultural shift away from pushing students too hard, which makes me glad. Obviously, we want to be successful and have a lot expected of us (which only increases as we progress through our careers), but we have to appreciate our own limits as well.

As someone who enjoys writing for fun, watching sports games, enjoying my weekend nights out with friends, going home to see family and friends (which requires an eight hour drive one way for me right now), playing musical instruments, and many more leisurely activities, I believe that doing so makes me better at what I do by keeping me happy and healthy. I believe that everyone can make time to have a life if they work hard enough to do so. Not only that, I also believe that they all SHOULD. It may take a little work to figure out how to balance everything, but it can be done and it is definitely worth it. As long as you find a program and an advisor that understands that you need to have a life outside of school, you will have the time that you need.

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.

Picking a thesis lab is a lot like dating

The lab where you do your graduate school thesis work is where you will be spending about 5 years of your life (or longer depending on your project, sometimes shorter). Whether you do it faster or slower, it is still many, many years of your life. Even more, this experience will be essential to prepare you for your career and so where you do your thesis really has implications for the rest of your life. It does not necessarily define it, but it sure is a lot better to get into a lab where you will be able to get the most out of the experience so that you can be productive and well-prepared to hit the ground running in your career.

Basically, it’s a pretty big decision. Just as big of a decision as picking a significant other, only you’re on a time frame. In my program, we are required to rotate in labs to get a better feel of them, sort of like casually dating a few people before picking someone to go steady with. Each rotation lasts five weeks. At the end of these 15 weeks, we must then go to a professor and join their lab. Let’s just say, I now understand truly why people say that they’re dating grad school and it’s not just about the time commitment.

Say you see a cute looking guy/gal at a party or in class or somewhere in public…

During our orientation, we had three days where faculty gave talks about their research so that we could figure out whose research interested us. We were just an audience for the professor; they had no idea who any of us were or who out of us were interested in their lab just as you would never know someone was checking you out (unless they’re pretty obvious about it).

…and you find out their name, so naturally, you look them up on Facebook…

Schools generally list their faculty on their websites so you can look them up and read a snippet about their research. Additionally, they often list their notable papers that you can then find online and read more about their research. This gives you background information on their work and helps you figure out if you’re truly interested in their research topic. Depending on how much information they have online, you can find out other things like what kind of awards they’ve received, the size of their lab, and the kind of journals where they tend to publish.

…you think you like what you see and so you decide to make a move…

Not all professors require it (they often mentioned it in their talks), but it is a good idea to send an e-mail to those professors you would like to rotate with to introduce yourself, explain that you’re interested in their work and why you are interested (which is where doing background research about their work can come in handy), and possibly argue why you would be a good addition to their lab. If you would like to be so forward, you can then ask if they would like to meet and discuss the possibility of rotating in their lab and what projects are available for rotation students. It’s kind of like asking someone on a date.

…Wow, they said yes! Now you actually have to go on that date…

So the professor said they would love to meet with you, cool! You meet them in their office (usually) and they try to get to know a little more about you – what your previous research experience has been, what you want your future research to be, why you want to be in their lab (often more in depth about the things you wrote in your e-mail). Then they tell you about their research (which can get lengthy as professors LOVE to talk about their work… I usually set aside an hour or so when I meet with a professor). Perhaps you both really like each other after these discussions and it progresses to actually rotating in their lab, then you get on the topic of rotation projects. Yay!

Since there are so many students in my class and our interests may overlap, just because there is mutual interest between student and professor doesn’t mean that you’ll get to rotate with them. We list our top six preferences for professors and a committee then goes through to optimize our placement so that everyone gets the highest choice possible – say six people list one person as their first choice but that person is only taking one student at a time, five of those people will not be getting their
top choice. If a professor REALLY likes you, they can increase your chances by giving input to the committee that they’d really like to have you as a student.

…You understand that the person may be putting on an act, so you try to find out more about them from people that know them…

Grad students are likely to tell you the honest truth about the lab. They understand what you are going through having gone through it themselves and so they generally are willing to tell you straight up what is good and bad about the lab. Maybe the professor seems really nice when you meet them but has been known to actually scream at his students (true story, glad I found that out before I put him as one of my top choices). Obviously he’s not going to tell you that he does that but the grad students definitely will.

…as you’re not in a steady/exclusive relationship yet, you can go ahead and flirt with other people and you take full advantage of the opportunity…

No matter how much you want to join a particular lab, it is in your best interest to talk to many professors to really find your best fit. Whether their lab becomes one of the three where you rotate or not, they can still be a good connection for possibly being on your thesis committee (a group of professors that oversee your progress and ultimately decide when you can graduate with a PhD), teaching a class that you TA for, or teaching a class that you actually take. You may feel like a player, but it’s okay because the professors are likely talking to more students than they’ll be taking into their lab too.

…the stars align and you start regularly dating a person…

The committee takes the list of six preferences from each student and works their magic to satisfy the students and professors to the best of their abilities (a HUGE challenge). Voila! For the next five weeks you will be in a certain professor’s lab.

…you keep the fire alive in the relationship…

Nothing is set in stone yet, so you need to continually show that you would be a good addition to the lab – a good mate. As a rotation student (and later as a permanent member of a lab), it is important to show interest in the work. The professor/grad students may give you papers to read and discuss with them. You can even go beyond that and find more papers related to those given to you. You also do lab work and try to be as productive as possible. You work long hours to show your dedication. You just generally try to act as a student who will be a good contributor to the professor’s research goals (and if you’re genuinely interested in the lab, all of this just comes naturally!)

…you get to know their friends and hang out with them…

It’s always important to be able to get along with your significant other’s friends and of course have their approval. In grad school, this is important too. You try to get to know the graduate students that are already in the lab to see if you’d get along as coworkers. The social dynamics of the lab can sometimes make or break your experience. These people can potentially help you adjust to the lab and learn the methods related to your work, and potentially collaborate with you on your projects.

…finally, you decide to get serious and become exclusive – you have your match!

After three rotations in different labs, you approach the professor you want to advise you on your thesis work and ask to join their lab. Assuming that they haven’t already had others approach them and so there are still positions available, they may say yes and you then have your thesis lab! Sometimes others get to the professor first and they fill the available spots in their lab so you’re out of luck there. You then approach your second choice. If all three of your rotations are either incompatible with your personality/research interests/work ethic, you may not get into any of your rotation labs. There is an option to do an extra rotation during winter break, but this is a last resort. Ultimately, the program will do its best to get you matched to a lab.

Say the person you ended up with isn’t the best (maybe you didn’t find out everything you should have before making a decision). There is still an option to break it off and go steady with someone else.

I have heard a few cases where students joined a thesis lab and a few months later joined a different lab (even a case where this happened a few years into the thesis.) It’s not optimal as it sets you back but it can be done. In fact it’s better to start over after a little while than be in misery for your whole thesis or risk not being able to complete it.

This is what myself and the rest of my peers are going through this fall. We are currently awaiting the placement for our second rotation. Starting on December 9, we will be able to officially join a lab (happy birthday to me!)