Beyond the Paper: A Conversation with Dr. Paulo Ávila-Gómez, Dr. Yuto Shingai, and Dr. Sabyasachi Dash

Interviewed by Dr. Paige N. McKeon, September 23, 2024

During sepsis and systemic inflammation, the blood brain barrier and endothelium are affected, which can impair cognitive functions and accelerate dementia. However, the unknown precise contributions of the cerebral microvasculature to sepsis-induced cognitive decline and the lack of standardized animal models represent major roadblocks to treatment development for dementia and other neurodegenerative diseases. To address these gaps in knowledge, Ávila-Gómez, Shingai, Dash, and colleagues validated a mouse model that recapitulates characteristic pathophysiological events in sepsis-induced cognitive decline. They identified key molecular, neural, and functional cerebral microvasculature changes acutely following sepsis that contributed to neuroinflammation and persisted up to 1 month following recovery. The findings and experimental strategies used in this study will be useful for further exploration of the mechanisms underlying inflammation-associated cognitive impairment, and to identify and develop novel therapeutic targets for neurovascular and neurodegenerative diseases.

“Research can give you an apparently never-ending succession of obstacles and doubts with occasional eureka moments of joy. […] You make great memories during good times, but it is during the not-so-good times that you really learn.” — Paulo

Dr. Paulo Ávila-Gómez (left), Dr. Sabyasachi Dash (center), and Dr. Yuto Shingai (right)

You each worked in Dr. Teresa Sanchez's lab following prior lab experiences overseas. How were your respective transitions into this lab? What drew you to this lab and/or this line of research?

Paulo: During my PhD, I conducted research in stroke with a translational approach, studying the disease from both a clinical and preclinical point of view, and most of my research was focused on the direct effects of the disease. As I progressed into my thesis, I became increasingly interested in understanding the cellular and molecular mechanisms that were responsible for these changes and became determined to learn how to study these pathways.

One of the key events that enticed me the most was the damage to the blood brain barrier (BBB) and the endothelium following brain injury, as it was not only related to stroke but also to other neurological conditions such as Alzheimer’s disease. Dr. Sánchez’s lab was the perfect match for my interests, both in their research lines and work philosophy. During the interview process, I was able to present my thesis project to Dr. Sanchez’s lab and discuss ideas with all the lab members, which was both rewarding and exciting. Moreover, my PhD mentors were also very supportive of my decision to pursue postdoctoral training overseas, which further encouraged and reassured me in my decision.

Yuto: Originally, I was a Japanese neurosurgeon working primarily in clinical practice. As a specialist in surgical treatments for cerebrovascular disorders, the prevention of secondary brain injury caused by endothelial dysfunction is an important theme to address daily clinical needs. Our lab has deep expertise in various brain injuries and functional impairments caused by endothelial dysfunction and given the longstanding connection with my institution in Japan, I was accepted as a postdoctoral researcher. Although there were complexities in procedures due to studying abroad during the COVID-19 pandemic, with the support of the PI, I was able to smoothly transition into the lab.

Sabyasachi: I had come across a few studies on the role of sphingosine-1-phosphate receptors in the pathology of neurovascular diseases. Prior, my PhD thesis focused on studying the molecular effects of cocaine and its interplay with HIV in the dopaminergic circuit. I had developed a strong interest in the BBB space by then. Realizing that Dr. Sanchez’s lab studied various targets on the endothelial compartment of the BBB routinely, I was drawn into the lab. Also, Dr. Sanchez was inclusive and supportive, and ensured a smoother transition to her laboratory for my postdoctoral training.

What are your current positions? What are your career goals and how have your experiences shaped these goals?

Paulo: I am currently in my second year as a postdoctoral associate in Dr. Sánchez’s lab at Weill Cornell Medicine. My career goal is to be able to conduct research on neurovascular diseases and healthy aging. I was born and raised in Galicia, a region in the northwest of Spain with an older population and a large incidence of neurovascular diseases. This situation is one of the motivators that pushed me to pursue a PhD focused on ischemic stroke and neurological diseases. During my PhD, I had the opportunity to learn animal models of different neurological diseases and to conduct clinical research with a translational approach. Now, during my postdoctoral training, my objective is to expand my understanding of the mechanisms behind neurovascular injury and neuroinflammation, and to contribute to the development of additional therapeutic options for these patients.

Yuto: Currently, I work as a neurosurgeon at a university hospital in Japan. My career goal is not only to refine my surgical skills and perform many surgeries as a specialist in cerebrovascular disorders but also to become a surgeon-scientist who can remain in academia, identify research themes that address clinical needs, and develop studies to solve those problems. In this regard, the basic research I conducted in the lab was an invaluable experience, helping me to assess what molecular biological approaches are necessary to meet clinical needs. However, through my basic research experience in the Sanchez lab, I also realized that it is quite challenging to pursue molecular biology research at an international level while simultaneously working as a clinical surgeon. That said, the greatest advantage of being a surgeon is the access to patient samples and the ability to continuously identify clinical needs. My goal is to build good connections and collaborations with basic scientists to achieve meaningful results.

Sabyasachi: I am a Senior scientist at the rare disease unit of AstraZeneca. I aim to contribute towards successful drug discovery campaigns that will produce live saving drugs for rare disease patients.

Being at Weill Cornell Medicine and in the Tri-Institutional network (Weill Cornell, Sloan Kettering Cancer Center and Rockefeller University) in Manhattan is a blessing that several trainees don’t realize. As a postdoctoral researcher in a cut-throat environment, one needs to strategize and build a framework to grow in their career. I was fortunate to have several mentors within Tri-I with whom I consulted regarding the same. Dr. Sanchez gave me the opportunity to lead two drug discovery programs in collaboration with big-pharma industry partners, where I obtained the first-hand experience to learn about how industry thinks and what sort of strategy is used to initiate a successful therapeutic campaign. This helped me immensely by not only giving me productive training, but also by developing and strengthening the skills necessary for an industry transition.

In terms of research experiences, I ensured that I was fully focused and understood my research plans to the best. I also put in efforts to strengthen my scientific communication through short pitches (elevator pitch, 10 min talks etc.) to be able to communicate in simple and complex ways depending on the audience.

“I believe that nothing you work hard on is ever wasted—it all becomes part of your strength. Therefore, while keeping the image of the person you aspire to be, setting a close goal of doing your best in your current situation is important.” — Yuto

“Be motivated and driven. Identify the purpose of your training and the goal.” — Sabyasachi

What advice do you have for young research investigators, both in the lab and as they try to figure out their futures?

Paulo: Research can give you an apparently never-ending succession of obstacles and doubts with occasional eureka moments of joy. To me, the biggest game-changer has been learning how to navigate through the ups and downs, to cherish and celebrate exciting discoveries, and especially to stay tenacious and flexible during hurdles and roadblocks. You make great memories during good times, but it is during the not-so-good times that you really learn. My advice both in and out of the lab would be to advocate for yourself, try and fail often, and enjoy the process.

Yuto: In this paper, I focused on endothelial dysfunction and brain impairment related to sepsis, which is somewhat distant from my original specialization. However, I believe that working with a shared purpose alongside the PI and other postdoctoral researchers to focus on a specific research area not only deepens insights within that field, but also broadens perspectives in other areas. Having the attitude of focusing on what is in front of you and deepening your understanding is crucial for ultimately achieving a lot. I believe that nothing you work hard on is ever wasted—it all becomes part of your strength. Therefore, while keeping the image of the person you aspire to be, setting a close goal of doing your best in your current situation is important.

Sabyasachi: Be motivated and driven. Identify the purpose of your training and the goal. Set the goal and then assess whether your efforts are positioning you to achieve your goal. If not, then don’t delay – go back to the drawing board, and re-strategize. Make sure to communicate clearly about your career goals with your PhD or postdoc advisor. Take actions based on what you like and what you want to accomplish.

You were co-first authors on this publication. Would you like to talk about your experiences collaborating and what made it so successful?

Paulo: The experience has been very rewarding. I joined the lab in April 2023, and Yuto was the person whom I worked the closest with, as he was the one who taught me about the animal models of sepsis and the behavior tests. It has always been very easy to coordinate and work in tandem with him, either conducting experiments, discussing data, or drafting the manuscript.

Even though I did not have the chance to work with Saby in person, he generated critical data for the project before I joined the lab, wrote very detailed protocols and always had very nice feedback and insight for the draft, which was extremely helpful for completing the paper. Overall, I think everyone made significant contributions to the paper and were supportive to each other in order to address the gaps in our research.

Yuto: Because we each came from different backgrounds, we each had our areas of expertise. This allowed us to progress in our respective fields of strength and then integrate the results. By sharing our findings with each other, we were able to achieve many outcomes in a short period, and being closely involved with the other two's research deepened my own knowledge. I believe we were able to fully utilize the benefits of working collaboratively.

Sabyasachi: We cared about robust and reproducible results. We were fine with our collaboration as I had already transitioned from my postdoctoral position to my current role in late 2022. I presented a major chunk of this published study at the 2022 KEYSTONE Neurodegeneration and Neuroinflammation summit, where I had received promising feedback and attention from the audience. 

“Because we each came from different backgrounds, we each had our areas of expertise. This allowed us to progress in our respective fields of strength and then integrate the results.” — Yuto

“Science without hurdles is...not fun. There were several technical and mental hurdles. [...] We just made sure that we all worked as one unit, and we did.” — Sabyasachi

What were the hurdles you faced in this research and how did you address them?

Paulo: Although I was familiar with neuroinflammation, I had never worked in the sepsis field or conducted research in a mechanistic fashion. Moreover, it was my first-time learning behavior tests and conducting several techniques and procedures that had been optimized in our lab, such as the isolation of cerebral microvessels. I think the key to overcoming hurdles was communication, openly discussing experimental approaches, data, and results in the lab, and supporting each other during the process.

Yuto: The behavioral assessments were not stable at first, and many trials were needed. By adjusting the experiment times and standardizing the management methods of the mice before and after the behavioral evaluations, we were able to obtain stable results. However, I believe this was the most challenging part of the process.

Sabyasachi: Science without hurdles is...not fun. There were several technical and mental hurdles – be it optimizing and repeating the experiments in batches, which was strenuous, or ensuring that the animals acclimatized well prior to behavioral studies. We just made sure that we all worked as one unit, and we did.

How was your experience with the eNeuro review process? How did it compare to other publication experiences you each have had?

Paulo: The review process was great. Reviewing times can sometimes get long, which was not the case with eNeuro. The referees’ comments helped us improve our manuscript and the feedback from the journal in terms of timing and genuine interest in our research was great, and helped ease the submission process. Overall, the experience with the journal has been excellent.

Yuto: Compared to others, I found the review process to be clear and smooth.

Sabyasachi: eNeuro is a great journal. I personally love the studies that are published in eNeuro and the review process. In fact, one of my publications from PhD thesis was also published in eNeuro.

Learn more about the Sanchez lab.

Read the full article:

Molecular and Functional Alterations in the Cerebral Microvasculature in an Optimized Mouse Model of Sepsis-Associated Cognitive Dysfunction
Paulo Ávila-Gómez, Yuto Shingai, Sabyasachi Dash, Catherine Liu, Keri Callegari, Heidi Meyer, Anne Khodarkovskaya, Daiki Aburakawa, Hiroki Uchida, Giuseppe Faraco, Lidia Garcia-Bonilla, Josef Anrather, Francis S. Lee, Costantino Iadecola, and Teresa Sanchez