Interview with Ann Stowe, who studies the neuroimmune mechanisms underlying stroke recovery at UT Southwestern
With PhD in Molecular & Integrative Physiology at the University of Kansas Medical Center, Ann Stowe embraced translational research by pursuing postdoctoral training in a one-year clinical trial at the Landon Center on Aging, at the University of Kansas Medical Center. She then moved to Washington University in St. Louis to continue postdoctoral training in neurophysiology. Stowe joined UT Southwestern in 2010, where she is currently Assistant Professor in the Neurology & Neurotherapeutics Department. Stowe is invested in Science communication and Policy.
What is a stroke and what led you to study it?
Stroke occurs when an area of the brain loses blood flow to it, which can happen either when a brain blood vessel gets clogged (i.e. ischemic stroke) or a blood vessel ruptures (i.e. hemorrhagic stroke). About 88% of strokes are ischemic, which is also the type of stroke we induce in the lab. The brain stops functioning without blood-derived oxygen and glucose delivery, creating an area of injury known as an ‘infarct’. Depending on where the infarct is located in the brain, the loss of function could manifest as a disability. This is most often why people go to the hospital, because they lose the ability to talk or move a side of the body. Unfortunately, this often remains a permanent disability. In fact, stroke is the leading cause of long-term adult disability in the United States. But there are also ‘silent strokes’ that are called that because the area of the brain that is injured doesn’t present as a loss of function.
Photo: Deprived of oxygen and other nutrients, the brain suffers damage as a result of the stroke.
To be honest, it was serendipity that led me to the field of stroke research. At KU Medical Center, Dr. Randy Nudo is a world-renowned researcher investigating the mechanisms of stroke recovery, particularly how the brain reorganizes to recover lost function, which is termed ‘functional plasticity’. I entered his lab without actually having a prior neuroscience class, but I was so interested in his work, he (thankfully) trusted that I could learn the basics! For my thesis work, I was particularly drawn to studying how other areas of the brain, outside of the infarct and thus uninjured, support plasticity and functional recovery. My lab to this day still investigates mechanisms that contribute to long-term plasticity after stroke. This is particularly relevant as the greatest recovery for stroke patients occurs over the first 3 months after stroke onset, though this can continue for years after the injury. Supporting long-term plasticity is critical for improving the quality of life for millions of people worldwide.
What events marked your scientific career? What lessons can you share from those events?
I would say there are a few key events in my training that have stayed with me over the years:
- My first journal club presentation: As mentioned previously, I entered the Nudo lab without a neuroscience background. I was therefore utterly panicked when asked to give my first journal club presentation about 3 months into joining the lab. I had previously studied leukocyte (i.e. white blood cells) interactions with blood vessels upon exposure to low oxygen, so my background was systemic inflammation. I therefore chose the Enlimomab trial (PMID: 11673584). This was a drug trial to block leukocytes from moving into the brain by not letting them stop in blood vessels, which is required for egress. Those stroke patients that received the drug had higher death rates, and for those that survived, worse recovery. While the paper cited several negative reasons for the failure, I wrote in addendum that perhaps leukocytes are required for recovery after stroke. This is still the defining focus of the lab: teasing out which immune responses in the brain are detrimental, and which responses are required to support plasticity and functional recovery after stroke.
- The move to Washington University in St. Louis: My undergraduate and graduate degrees, as well as my first postdoc, where all at the University of Kansas. So when it looked like I was staying at KU forever, my mentor Dr. Herb Geller (at NHLBI) asked me to discuss this career plan with a program officer at NINDS, which is the NIH institute funding stroke research. At this meeting I was told that no matter how good my science, if I never moved from Kansas I would always have an uphill battle to receive funding at the national level. This was really difficult to hear, especially as I had two kids and my husband, Matt, was faculty in KU’s School of Special Education. Fortunately, Matt understood the importance to my career, and we moved to St Louis for a second postdoc at Wash U in 2007. This was probably the single best thing I did for my scientific development, not only for the outstanding training in new techniques, but for the exposure to other great scientists that I continue to collaborate with today. The collective scientific community may be a softening to the concept of staying in one city or at one institution, which I think is good for those limited to a location, but I certainly understand now the logic and benefits of broadening scientific exposure.
- My first R01: Well that was a glorious day! This had been my fourth attempt at the R01, so I was a little worried it would never happened. As I looked back on the first R01 submission, I laugh because I proposed to make 4 genetic mouse lines, a technique for which I had no experience. Absolutely no experience. This was a very novice mistake, and looking back I wish that I had sought out an experienced colleague (or three) to look over the grant and tell me that no one would ever fund me for generating mouse lines. I think in general I am often loathe to bother people with reading over papers and grants, but there are plenty of colleagues who would be happy to help if I just asked… a lesson that is much more beneficial if learned early in one’s career.
What led you to UT Southwestern and what do you like most of being here?
While I was at Wash U, I was awarded a Fellowship from the Hope Center for Neurological Disorders, with Dr. Mark Goldberg as director. After a couple years at Wash U, my husband decided to look for a job in St. Louis and became the Director of Operations for the Hope Center. About 6 months into the job, Mark accepted the Chair of Neurology position hear at UTSW, and recruited both Matt and myself to the department. It was an amazing opportunity that was only possible because of the move to Wash U. I started my own lab as a faculty member of Neurology, which has been truly beneficial in developing the clinical aspects of my lab investigating neuroinflammation during brain injury. I think the collaborations I have with other UTSW faculty is what I have enjoyed most about being at this institution. I now have grants that span multiple diseases, both clinical and preclinical, with friends/colleagues in many departments on campus.
What do you most like doing in the lab?
Designing experiments. If I could get a job just designing other peoples’ experiments all day, I would take it in a heartbeat! We are getting ready to submit an R01 this summer, and in doing so I make this a lab event. As I have already learned, multiple inputs into the experimental design are critical for a successful grant. Therefore, for this R01 submission the lab has had multiple meetings this spring ironing out the specific aims, discussing what preliminary data are needed, and in general honing the hypotheses presented and the experiments needed to test them. I think this is a great learning tool for my graduate students and postdocs, as they begin to understand that science is not a silo, but requires the integration of multiple techniques, disciplines, and even opinions in order to succeed.
Photo: identifying ischemic brain stroke
What challenges do scientists face at the moment?
I hate to sound trite, but funding is probably the biggest challenge for current scientists, as well as future scientists. It is difficult to encourage graduate students to choose a life of academic research when they see the faculty around them struggling to get grant funding. I fear that in this environment we are losing a lot of great scientists because of the uncertainty of career success. Which blends into my personal greatest challenge… time management. I did not get my first R01 funded until I had published my first paper on the role of B cells in stroke recovery (the focus of the grant). Publications are critical for grant funding, as they demonstrate to grant reviewers my ability to generate successful, peer-reviewed science. But it is difficult, I think particularly for early faculty, to balance conducting experiments, writing papers, and writing grants, all while maintaining healthy aspects in other areas of life. Unfortunately this is not a problem unique to science; everyone needs to establish right work-life balance.
What can scientists do to educate the community on the value of science and the need for support?
Well, I had a two-year old when I entered grad school, so most of my scientific career has included trips to local grade school and high schools to talk about careers in science. I think this is one of the best ways to generate a love for science in kids and a better understanding of the importance of science in improving the quality of our lives. This is particularly important for educating people about the benefits of animal research. More recently, I was awarded an Early Career Advocacy fellowship from the American Physiological Society. This was an outstanding opportunity to be trained in advocacy on Capitol Hill, as I went to Congressman to predominantly advocate for increases science funding. I think it is great for scientists to understand the impact of federally funded research on economics at the local, state, and national level, and what means are at our disposal to gather more popular support for scientific research.