Dr. Vanessa Coelho-Santos
Junior Group Leader Coimbra Institute for Biomedical Imaging and Translational Research
Postdoctoral Fellow Seattle Children's Research Institute
PhD in Ageing and Chronic Disease University of Coimbra, Portugal
Growing up in a small village in Portugal, Dr. Vanessa Coelho-Santos did not have access to scientific role models. Instead, she came to know and appreciate science through books. Then, through a high school program—Ciência Viva—she had an opportunity to do a summer internship in a science lab. Vanessa was hooked, and since then she has been driven by a passion for learning and discovery. Today, Vanessa is a La Caixa Junior Leader at Coimbra Institute for Biomedical Imaging and Translational Research, where she studies neurogliovascular development.
During the Ciência Viva internship, Vanessa worked in a hospital, in a small lab that was trying to understand the genetic underpinnings of cancer. She helped perform PCRs on cancer patients’ blood samples as well as blood samples from their relatives. Using this information, Vanessa constructed genealogical trees to determine how certain cancer-related mutations were transmitted through families. While she was not particularly passionate about cancer or genetics, this experience left her with a clear conclusion: she loved working in a research lab.
Keeping her newfound interest in mind, Vanessa majored in biotechnology at the Polytechnic Institute of Coimbra. While she knew that she was interested in science, she was not yet sure which topics most excited her. She chose the biotechnology major because it was the broadest and thus would give her exposure to many different facets of science. During her undergraduate studies, she worked in Dr. Cláudia Nunes dos Santos’ lab studying how plant-derived antioxidants can be protective in cellular models of neurodegeneration. This was Vanessa’s first exposure to neuroscience, and she felt driven to learn more about the brain. She applied to the Cellular and Molecular Biology master’s program at University of Coimbra, hoping to specialize in neuroscience.
The transition into the master’s program was more difficult than Vanessa had imagined. Rather than taking several semester-long classes as in university, the master’s program involved taking a new class each month, which felt like barely enough time to learn the material. Despite being overwhelmed and battling the creeping sensation of imposter syndrome, Vanessa pushed through, learning to balance the coursework with her lab work. She had joined the lab of Dr. Ana Paula Silva who focused on the neuroinflammatory effects of drugs—both drugs of abuse and legally prescribed medications. Vanessa’s master’s project focused on how methamphetamine affects microglia, the brain’s innate immune cells. She found that low concentrations of two pro-inflammatory cytokines—TNFalpha and IL-6—are protective against methamphetamine-induced cell death in a microglial cell line.
After obtaining her master’s, Vanessa received a fellowship that allowed her to remain in the same lab to continue her research. She switched from studying microglia to studying brain vasculature, and it was love at first experiment. Vanessa was immediately entranced by the importance and power of the blood-brain barrier, the series of properties unique to brain vasculature that allow them to tightly control what can move from the bloodstream into the brain. She realized that it was the vasculature—which sits at the interface between the brain and the periphery—that determines the microenvironment of the brain. After a year and a half of fellowship, Vanessa decided to do a PhD in order to dive further into studying the brain’s blood vessels. Staying on in the same lab, she began a project focused on understanding the effects of a commonly prescribed ADHD drug, methylphenidate (better known as Ritalin or Concerta). Using a rat model of ADHD, Vanessa found that the drug had a more deleterious effect on the blood-brain barrier of control rats compared to Spontaneously Hypertensive rats (the ADHD model), leading to increased neuroinflammation in the control group. In contrast, in the Spontaneously Hypertensive rats, at the right dose, methylphenidate improved behavior and neuroinflammation. Her discovery underscores the importance of correctly diagnosing children before prescribing medication.
As she was wrapping up her PhD, Vanessa received a Luso-American Foundation Fellowship that allowed her to do a 6-month internship in a lab in the U.S. During her graduate work, Vanessa had had the opportunity to perfect many techniques, including cell culture, primary culture, animal behavior, and work with human brain and blood samples. To expand her skillset, she wanted to learn 2-photon microscopy, to watch vascular cells and blood flow in real time. She researched which labs were working in this space and began emailing PIs. Some did not respond at all, while others were wary of the short time span that her fellowship provided. But one PI said yes, so she packed her bags and moved to Charleston, South Carolina to work with Dr. Andy Shih. Although she did not feel particularly at home in Charleston and struggled to navigate the city without a car, the lab itself was a perfect fit. After just one month, Andy asked if she would like to come back to his lab for a postdoc after finishing her PhD. She enthusiastically accepted the offer.
After receiving her PhD back in Portugal, Vanessa again traveled to the U.S., this time to Seattle where the Shih lab had recently moved. She remembers meeting with Andy at the beginning of her postdoc. He asked, “What is your dream project?” It felt like the most wonderfully important question she had ever been asked. She told him that she wanted to study the neonatal development of neurovasculature using 2-photon microscopy. There was no real precedent for this, so Andy told her he could teach her the technique on adult mice, but then it would be up to her to adapt the technology for studying pups. Vanessa rose to the challenge, learning tricks for working with young animals and 3D printing lots of new, miniaturized equipment. She hopes that this new technique, now published, will enable herself and others to learn more about neurodevelopment, and particularly about the development of the neurovasculature and its associated cells.
From the first day of her postdoc, Vanessa was sure that she wanted to lead her own lab someday. Inevitably, she sometimes questioned whether she was capable of achieving this goal, but the goal itself remained constant. As she worked towards adapting 2-photon microscopy for neonatal brains, she asked Andy if she could start a couple side projects through which she could mentor technicians. She enjoyed and felt empowered by this mentorship, becoming even more confident that she was on the right career path. As she was nearing the end of her project in the Shih lab, Vanessa began applying to fellowships that would allow her to start her own group back in Portugal. After receiving the La Caixa Postdoctoral Junior Leader fellowship, she began her journey as an independent researcher at Coimbra Institute for Biomedical Imaging and Translational Research.
In her lab, Vanessa wants to use the tools she developed in Seattle as well as other imaging technologies to interrogate the cellular and molecular events that govern the formation of the neurogliovascular unit during neonatal development, and how disease or injury might affect this process. She is particularly interested in neurovascular coupling, the processes that lead to increased local blood flow following neuronal activity. Surely, witnessing Vanessa’s passion for neurovasculature, her future trainees will also fall in love with the brain’s blood vessels and the power they hold for controlling what happens inside the brain.
Listen to Margarida’s full interview with Vanessa on March 8th, 2023 below!
