Written and Interviewed By: Mericien Venzon

This blog series will go ‘Behind the Paper’ for one of JRNLclub’s most outstanding recent uploads. Our intention is to highlight the often overlooked human element of the impactful science that our videos showcase and help younger trainees see parts of themselves in the scientists they admire.

Dr. Jennifer Jenks, a MD/PhD candidate at Duke University, sat down with JRNLclub ambassador Mericien Venzon to talk about her recently published PhD work and the impact of having women physician-scientist mentors in her early career. In her Science Translational Medicine publication, Antibody binding to native cytomegalovirus glycoprotein B predicts efficacy of the gB/MF59 vaccine in humans (JRNLclub video), Dr. Jenks and colleagues highlight the importance of the native, cell-associated gB conformation in future CMV vaccine design.

Your study was phenomenal and it has important implications on vaccine development. The differences were particularly striking between adolescent and postpartum groups. Did you encounter any specific challenges during the study and if so, how did you work through those?

I think some of the challenges that I encountered were actually due to my initial inexperience in this kind of translational research project. This type of study involves complex statistical analyses and modeling, and a lot of that had to be planned upfront, even before we had collected any data. I worked with a statistician to develop a stepwise process for how we should analyze the data, and while writing up this plan, I was still learning the actual wet lab techniques. I was learning a lot as I went.

I overcame this challenge by working with my many mentors. I had Sallie [Permar], my PI, who brought the basic science expertise and experience with epidemiological studies, and our statistician Dr. Cliburn Chan. He's also co-senior author on the paper and he oversaw all of our statistical analyses and the blinding. I think the three of us together were able to set the study up such that once we had a plan in place, the study execution actually went fairly smoothly. Now that I've had some experience with this type of translational work, I better appreciate how some other similar studies, like case-control studies, are designed.

What about the findings of your study excite you the most?

I think the implications for vaccine design are really interesting. One of the major challenges for developing a CMV vaccine is that once CMV enters a host, it can establish a lifelong infection that can’t be cleared, and this virus can be transmitted, for example from a mom to developing fetus, or can reactivate in an immunocompromised patient. Also, once someone is infected with CMV, they can still be reinfected with a second strain, so even natural infection doesn’t induce immunity. So, you can imagine that developing vaccines that can prevent infections, or at least disease, is really challenging. We essentially have to make vaccines that are “better” than natural immunity.

I thought that this aspect of this kind of vaccine work for CMV is really interesting. What our paper was trying to get at is how there might be some specific immune responses that we would want to enhance with a vaccine. Our study looked at sera from previous participants in a partially effective clinical trial of a candidate CMV vaccine and found a “signature” antibody response associated with protection. This sera antibody binding response might be one way of assessing a candidate vaccine in pre-clinical animal studies or even during the course of a trial before the final primary outcomes are measured. I think it's interesting to ask these questions in this particular field.

More broadly, how did you first get interested in science and medicine?

I was interested in science and medicine pretty early on. As a high school student, I knew that I was interested in working with people, and I really loved the idea of taking care of people for a career. I got involved in research early on in anticipation of hopefully going to medical school. I was a freshman in college when I reached out to an allergist/immunologist named Kari Nadeau, and she was doing work on food allergy and autoimmune disease. I worked with her for six years, studying regulatory T cells in primary immunodeficiencies and allergies. From that experience, I learned so much about immunology in general, and I just thought it was such a cool way to learn about the body. The immune system really does go everywhere. It interacts with itself and interacts with the outside. I knew that I wanted to do something in that field long-term as part of my career. That's how I ended up doing an MD/PhD. During my research career, I've also developed an interest in host-pathogen immunity, which is how I ended up in microbiology and studying virology.

Who inspires you?

I feel like I've been really lucky to have worked for the some of the people who I admire most in science. I chose to work with my PI Sallie Permar for my graduate studies because I'm interested in her science, and also because I think that she is a mentor to me in a lot of ways. She’s a physician-scientist who still does clinical work in pediatrics and yet is able to manage a lot of diverse, interesting research projects. She also makes time for her mentees. I’ve also gotten to uniquely see her career grow, rising up the stages as faculty. I think that it's really wonderful to see female PI’s in leadership and to be able to see these transitions as a trainee.

In addition to your mentors, what other sources of support have you had as a woman in science?

Actually, a lot of my lab environments have been very female empowered. I’ve worked for two female PI’s, both of whom are physician-scientists, and the majority of the scientists in each lab were female researchers. I’ve felt really well supported as a woman in science. I also think seeing all of these different early career scientists learning and beginning to establish their independence as investigators has been wonderful.

The journey of a physician-scientist is a long one. What would you tell your younger self?

I would say to my relatively-past self to make friends along the way who are going to be along the journey with you. My MSTP colleagues have been some of my greatest sources of support because we all started medical school at the same time, we're all on track with each other, and we have all experienced the same kind of struggles. Having close friends, especially ones that understand what the process is like, is really important.