We got in touch with Lisa Wagar, a recent graduate of our department, to see what she’s up to now, and to get some feedback on her graduate experience. As always, our alumnus has some interesting stories to tell and important life lessons to share.
When did you graduate from the Department of Immunology and what’s next?
I defended in August, and less than a week ago packed up everything I own into two suitcases and headed for a postdoc at Stanford. My goal has always been to pursue research, and I think I had a relatively good PhD experience – I was encouraged to continue down this route despite the usual research setbacks.
I would say that you have transitioned well into your postdoctoral fellowship, was it difficult finding a position and what influenced your decision?
All the PIs who I talked to about finding a postdoc position mentioned that it sort of happened “by chance”, something that never seems to happen to me. Then Mark Davis came to give an Easton Seminar quite a while ago, and his attitude towards pursuing human immunology really resonated with me. It was nice to hear from someone else who thought this was a major part of the immunology field that needed development. I contacted him around December last year, and he invited me to give a talk. The rest is (ongoing) history!
Is California as amazing as it is in my dreams?
First impressions here: it’s warm. People are nice. The science is hardcore.
What was your research focus? How did you decide on a laboratory?
My focus was on T cell immunity to influenza in humans. That included looking at seasonal vaccine responses, pandemic H1N1 vaccine responses, and the persistence of memory post-infection with flu. I’ve spent the last 5 years in Tania Watts’s lab (and I didn’t rotate initially). When I first met with Tania, she was clearly very enthusiastic about science, an absolutely crucial characteristic for a good PI! She was able to offer me a project in infectious diseases and human immunity, which were the two main things I was interested in pursuing
For those that may not be familiar with your work, can you introduce us to your studies?
Flu is a bit of an unusual pathogen, because although it’s an acute infection, it’s very good at mutating and re-infecting over the course of a person’s lifetime. As you can imagine, this can result in some interesting immune characteristics. The elderly are particularly susceptible to influenza infections and are also poorly protected by the seasonal vaccine. Therefore, we examined some of the phenotypes of flu-responsive T cells, and found that older people have T cells with some signs of “exhaustion” or “senescence” in their flu subset. When the markers were more prevalent, the subjects were more likely to respond poorly to the vaccine. Overall, we think that this could be a readout of immune health in older people. We found in a study of donors from a pandemic H1N1 infection and vaccination cohort that in general, T cell responses to flu are boosted only very transiently, and that by the time flu season rolls around again, your memory cell-mediated immunity is likely back to baseline. All of this has some interesting implications for vaccination, and some of these ideas have been passed off to other labmates and are currently being followed up!
What influenced your research choices and direction?
I had to go where the data was taking me. I struggled big-time trying to get some assays to work in the first couple years of my PhD, but it just wasn’t happening. We had to regroup and decide what else we could examine with the samples we had. Eventually I developed/optimized my own assays and got those working for me!
Can you comment on the current state of flu research?
It’s been a super hot topic lately. Between H5N1 (bird flu) and H1N1 (pandemic 2009), it’s become a very relevant pathogen to study recently. There are a few things that make it a difficult topic of study. First, infections are largely limited to the lung, while sampling in humans is almost universally peripheral blood. This lets you get a general readout of what’s going on, but you can never really know what’s happening at the site of infection. Second, the repetitive nature of the infection can make data interpretation difficult – are responses different in people who have been exposed 5 times? 10 times? What strains were they infected by? How many flu vaccinations did they have in that time? This can make a disconnect between humoral and cellular immunity. The worst thing, in my opinion, is that people are not routinely tested for flu infection when they have “influenza-like illness”, fever, malaise, aches, etc. It’s all very non-specific, which makes it difficult to pin down people who have recently had flu infections.
What are some of the difficulties you encountered during your studies and how did you overcome them?
Acquiring samples was by far the most difficult part of my PhD experience. Although many of you wonderful folks provided me with healthy donor blood samples, as I mentioned before, it’s hard to catch subjects who have recently been exposed to flu virus. Vaccination cohorts are easier to come by, but it is typically clinicians who are collecting the samples. You’ve got to work with what you can get, and ask some relevant questions based on the donors and timepoints available!
Did you encounter any roadblocks when trying to publish human work?
I think a lot of scientists and reviewers tend to brush off the results from human studies because the data is so spread out, but that’s real life! Certainly it is messier, and makes it more difficult to draw finite conclusions, but isn’t it still worth pursuing? I’m still learning how to provide the most compelling evidence with as many controls as possible. Reviewers are also used to asking for more experiments when they have questions about manuscripts – a lot of the time, this is just not feasible. You collect 3 or 4 tubes from your study participants, and that’s it. That’s all you’re going to get at that timepoint. The study I’m about to embark upon, they’re collecting about 1 mL of blood.
Don’t get me wrong, mice are amazing tools for immunology research. There are so many things we’ve learned from knockouts and transgenics that you could never really do in humans. I just think it’s a little sad that so many scientists propose these interesting experiments that *could* be tried out on human samples as well, but it never goes there; you can do basic research on human cells too. It seems that there is huge money available for clinical translation studies, but this is missing out on human basic research prospects, and it’s really a shame.
What was your worst and best day/week/ year?
Worst: going crazy trying to figure out for months why my plasmids were disappearing (bacteria fine, plates fine, minipreps fine, NO BANDS!). It was the water. The filtered water. Best: pulling together my work on cellular immunity in aging donors, and finding correlations with exhaustion!
What helped get you persevere in your studies?
Trying to remember that this is just a part of research. We all put huge expectations on ourselves, but sometimes science moves at its own pace. That and just because I want something to be true, or correlated, or sensical, doesn’t mean it works in nature!
What advice would you give to first-year students or a younger version of yourself?
Think about what you want to do (career-wise) now, not 4 years down the line when you’re less than a year from graduating. You can change your mind, but give yourself time to reflect on the options.
If you could change one thing about the Department of Immunology, what would you change? What would you keep the same?
I wish someone had told me my options way earlier, but I can see the dept is working on that now. I do love the way the courses are run – the focus is more on learning than studying/writing assignments. I was shocked to hear that some of my friends in grad school at other schools and programs are still taking courses in their 4th and 5th years!
Star Trek or Star Wars?
Star Wars. Mumbling to myself while analyzing with Flowjo, ‘these are not the cells you are looking for’.
Yuriy Baglaenko
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