Jennifer Alexander-Brett, MD, PhD
Dr. Alexander-Brett is a physician-scientist in the Division of Pulmonary and Critical Care Medicine. She completed her undergraduate degree at the University of Nebraska-Lincoln and her MD-PhD and medical training here at WashU/BJC. Her current research focuses on the role of cytokine mediators and lung epithelial stem cells in the development of chronic airway diseases.
“To this day, it’s hard to even find the right words to explain what that was like. But we all know that this won’t be the last.”
COVID hit, and it was wild because as critical care physicians, they told us, ‘OK, here’s what’s going to happen. You’re going to leave your lab. You’re going to go in the ICU starting tomorrow.’ I opened the first COVID ICU unit on a night shift, two days before my birthday. The unit was ready to go and waiting. All the rooms were set up, all the isolation PPE was there. We opened the doors, turned on the lights and off we went. Everyone was terrified of getting COVID, frankly. At first, to limit the number of people exposed, it was just the ICU nurse and the attending physician in the room. There were no fellows, no residents, no ancillary services coming in; everyone else was virtual. With no trainees present, I did all the procedures. It was just me and the nurse in the room for each of those patients. And very quickly, we were filled. In the early months we worked grueling schedules to cover the patient volume. At the very beginning, it was just mild cases. And then the real ICU patients came, the ones that were in multi-organ failure. All of them. There are no words for what that was like because it was just complete mayhem all the time and super hard physically, super hard emotionally. As the unit leader, I had to keep everyone calm in this environment, and at the same time, be terrified that I was going to get it myself through intubations. It was like, ‘OK, I’m going to get COVID now’ all the time. It was this twilight zone we were in. Everything else was locked down and everyone was home. The world was quiet, and then you walk onto the unit. It was loud and hectic and a completely surreal experience. I think for anyone who goes into critical care, you think you’re ready for something like this, but you’re not. Sure, everyone is going to do whatever they’ve got to do; it’s the job. But it was something incredibly traumatizing for everyone who did it. Especially the nurses, we lost so many of them, great critical care nurses who left the field. You just didn’t know when it was going to end, and for many it got to be too much, and this is the new reality now.
I think we’ve learned lots of things, and there’s lots of things to learn still. In retrospect, it was really tough. It really was. But also, on the flip side of that, I feel like a changed person. Not just as a physician-scientist but also as a human being. There are things I care a lot less or a lot more than I did pre-COVID. I want to hope and think that it’s made me overall a better person. I live for the moment much more now. I did a lot of waiting before. But now, I just go for it. To this day, it’s hard to even find the right words to explain what that was like. But we all know that this won’t be the last.
“I very much appreciated his enjoyment of creativity and his inventive spirit.”
I was born in Nebraska, which is not a very exotic place. It has a very low population density, mostly consisting of families of farmers. My mom had thirteen siblings, but I only have two younger siblings. I grew up in a rural area and then moved to a smaller town. There isn’t much outside of Omaha in Nebraska, and corn is everywhere. My grandfather was a self-proclaimed inventor of things and gadgets. He was always tinkering with projects. There is one thing that he liked to do every year that I really enjoyed. He would take out irrigation pipes and create this giant Christmas tree scaffold in the yard, stringing it all up with lights. Then he would stick a hose up in the air and shower the scaffold with water until it froze over, turning it into this giant ice tree with lights. It was beautiful. I loved it. Those were the kind of weird projects he would do. He created fountains and all sorts of objects that he designed himself, which were just strange and off-the-wall stuff. I very much appreciated his enjoyment of creativity and his inventive spirit. I also love the outdoors, and he taught me a lot about foraging, finding things in the land and identifying edibles. I think between those two things, my interest in the natural world increased, and the desire to understand how things work and fix them just sort of caught on with me.
“The corn was wet from the dew, cutting and splashing water in our faces.”
I had a variety of jobs in Nebraska, and my least favorite job was probably detasseling corn. It was a horrible job. I had to wake up early in the morning and ride out to the fields on a bus. Cornfields surrounded me everywhere. There were rows of plants that they wanted to cross-pollinate to create a specific hybrid corn. My task was to remove the tassels from the top of the corn that they didn’t want to pollinate. Machines would do the first cut, but it was very inefficient. Around 10–20% of the tassels were left, and we were the second group that went through by hand to pull the remaining tassels. It was tough labor — the fields were irrigated in the morning, so they were muddy and sloppy. The corn was wet from the dew, cutting and splashing water in our faces. We wore raincoats or ponchos, and gloves, but they inevitably get soaked because all the corn was wet. By the end of the afternoon, it was very hot and dusty, with lots of pollen floating around because it was corn pollination season. It was miserable. We worked around 12 hour a day, engaging in serious agricultural labor. At the end of the month, we would receive a check for around $600. It was a common summer job for kids in Nebraska, and we started doing it around the age of 12 or 13. Now, looking back at that experience as an adult, I think it’s kind of crazy.
“My first venture into protein biochemistry involved studying the protein complex known as Rubisco, which is the most abundant protein on the planet.”
I attended the University of Nebraska, which was basically where everybody went. As a Nebraskan, it was very unusual at the time to go to college outside of Nebraska. You either went to the university or you didn’t, and those were the two tracks. I received a scholarship and pursued a double major in chemistry and biochemistry at the university. During my freshman year, I met a teaching assistant in the Department of Chemistry who introduced me to X-ray crystallography, and I’ve been in the lab ever since.
Initially, I worked on modified amino acids that had chiral recognition properties, enabling them to distinguish between different enantiomers of a drug. If one enantiomer of a drug was known to be more effective than the other, it would be important to separate them. However, this was challenging to achieve using standard chemical purification methods. The substances I was working on had the potential to be chiral discrimination purification matrices. My first venture into protein biochemistry involved studying the protein complex known as Rubisco, which is the most abundant protein on the planet. I had to purify the Rubisco protein from Chlamydomonas algae. We were studying mutants that could grow in the dark and had spontaneously acquired mutations to adapt to low light conditions. We would grow large flasks of Chlamydomonas, spin them down, and then use sucrose gradients to purify Rubisco. Subsequently, I would set up crystal trays and grow massive crystals of Rubisco. Most protein crystals are microscopic, but Rubisco crystals were visible to the naked eye. They needed to be large because you required enough representative copies to determine the structure, especially before the time of CryoEM.
Interestingly, as we were preparing to collect crystallographic data, I was going on interviews for MD-PhD programs. In those days, they didn’t cover your trip expenses. So, to save money, I combined my data collection trip to San Francisco with my interview at Stanford. After completing my interviews, I asked them to drop me off at the linear accelerator so I could collect the data I needed. It was a good trip all around. But then Stanford was kind of weird about the fact that I declined their offer to come to WashU instead.
“Grad school is a time when you’re free to do science, delve into it, and really enjoy yourself.”
I developed a strong interest in protein biochemistry, and it wasn’t until my last year of undergrad that I decided pursue medicine. It was a late decision, and part of it stemmed from a rebellious sentiment against all the people in my life who thought, ‘You’re doing so well in undergrad and of course, you’re going to go to medical school.’ In that sense, I was pushing back against everyone because I didn’t want to pursue a career path that everyone expected of me. I wanted to carve my own path and figure it out for myself. I did the science, and I did some volunteer work in an ER during my last year. With all the different jobs that I’ve had and learning to interact with people, I felt that human connection was important to me. I think of my job as a physician as an expression of my humanistic side, while my scientific pursuits are much more analytical. I enjoy being in both worlds, so I decided to pursue a MD-PhD. I think it’s interesting the way that folks arrive at the decision to do MD-PhD because it’s such a long path and a big commitment. I think that the process that people go through when they decide to take that route takes a fair amount of introspection and time, especially for someone in their 20s.
Before I even knew about WashU, I had the opportunity to meet some people from WashU’s biochemistry department at a crystallography conference. I just really clicked with them. When I came here for an interview, I found the place and the people to be wonderful. Initially, I thought I would work for Gabriel Waksman. I rotated with him and was expecting to join in his lab. My second rotation was with Dave Fremont. At that time, he had recently started a collaboration with Skip Virgin studying a funky viral protein called M3 that could bind chemokines. They didn’t know what this thing did. I was like, ‘This is cool, and I definitely want to study that.’ I learned how to make M3 and tried to get crystals of the protein with various chemokines. I had a hit during my rotation, and we were on our way to getting the structure by the end of my rotation. I pretty much have to join his lab now. We did the structure, and my first grad school paper was a Cell paper, which was fantastic. I continued working on M3 chemokine structures with Dave. I was his second student, and to this day, I’m still friends with his first grad student, Mikey. We all still call him “number one”. We were a tight-knit group that worked together, and we had a great time in grad school. Grad school is a time when you’re free to do science, delve into it, and really enjoy yourself. You have no hard responsibilities, and you don’t have to worry about grants or data management plans.
“When you start looking at things from a different perspective, you begin to discover new aspects that nobody saw before.”
There is something very exciting going on in each project in the lab that I’m super pumped about. I think we have the potential to make some really interesting and novel observations in chronic pulmonary diseases. We have an interest in extracellular vesicle biology, which is a relatively new field that not many people in pulmonary field are working on so far. Because we are looking at diseases from a new angle, we found a lot of fascinating things that are spinning off into new projects. Just learning about the cargos, proteins and microRNA harbored by these vesicles and their potential roles in disease is like exploring a new frontier. When you start looking at things from a different perspective, you begin to discover new aspects that nobody saw before. We’re experiencing a lot of that in the COPD, and we’ve been able to translate those findings to chronic lung transplant rejection as well. Currently, the area where we are having the most fun and experiencing the most success is the human system and using mouse models to validate our findings. The mouse is great for a lot of things because you have so much control. You don’t have much control over human data. But when you can get human specimens with the abundance that we do, you can start to ask really sophisticated questions and learn really cool things about human disease. At present, we are uncovering fascinating aspects of IL-33 regulation in terms of its expression, secretion, and their roles in the context of COPD and asthma. We’ve also got these EV-associated biomarkers that has the potential to help us diagnose lung transplant rejections earlier than we can see them physiologically. These are two fun areas that we’re going to have some cool projects come out.
“I just have a lot of gardens and it’s more than I should have because I don’t really have the time to do all this, but it brings me so much joy trying.”
I’m a crazy plant lady, so I have a huge garden. I have a great rose garden and a peach tree. My flowers are my joy, but maintaining the garden is a full-time job. In fact, just this weekend I was out there gardening. I have this thing where I’m very much against invasive species, and honeysuckle is big problem around here. So, I was busy whacking some honeysuckle this weekend when, unfortunately, I accidentally jabbed myself in the eye. I thought I got a corneal abrasion or possibly something worse. I was going to have an eye appointment, fearing the worst, but fortunately, I think my eyes are better. I think going through medical school can sometimes make you a bit of a hypochondriac, always considering the worst-case scenario. I just have a lot of gardens and it’s more than I should have because I don’t really have the time to do all this, but it brings me so much joy trying.
Our three kids are also actively involved in the garden. One of my daughters is always picking the flowers that we grow. We also do a lot of outdoor stuff together as a family. We love hiking, paddling, and kayaking. I’m also into birds, my oldest girl takes care of them. I have a collection of bird feeders outside as well as birds indoors, two little parakeets. We have lots of good times with our kids. One of the girls recently completed a science fair project and I’m incredibly proud of it. The project has a fascinating premise. You see, we have lots of deer that frequently come through our yard, just chasing after all the stuff I grow. So, my daughter wanted to find out what types of food the deer likes to eat. We set up little plates with different food in front of the wildlife camera so she can see what the deer eat. We discovered that they are not fond of lettuce and lemons, which is understandable, I suppose.
Interview conducted and edited by Jing Chen, WUStL MSTP GR3
Twitter @WUSTLImmuno
This is a part of the #HumansofWUSTLImmuno series featuring members of our community.
