Dr. Cláudia Almeida

Principal Investigator NOVA Medical School, Lisbon, Portugal

Postdoctoral Fellow Institut Curie, Paris, France

PhD in Neuroscience Weill Cornell Medical College, New York

Inspired by Marie Curie’s biography, Dr. Cláudia Almeida wanted to be a scientist from a young age. This aspiration was driven in part by her desire to “run away from a boring life.” She was fascinated by the idea of scientific discovery and saw it as a powerful way to infuse her life with interest and purpose. Knowing that Cláudia wanted to become a scientist, her father—a medical doctor—suggested she study the brain because “that is the part of the body we know the least about,” and thus is the most ripe for discovery. Today, Cláudia is helping to unravel some of these mysteries about the brain as a Principal Investigator at NOVA Medical School in Lisbon, Portugal. Her lab studies how neuronal trafficking contributes to synapse loss in the brain in normal aging and in Alzheimer’s disease.

With her father’s words in mind, after earning her undergraduate degree in biochemistry, Cláudia began to seek opportunities in neuroscience. She entered a new neuroscience master’s program at the University of Lisbon, where courses covered material ranging from cellular and molecular mechanisms to clinical neuropsychology. Cláudia loved thinking about the connections between the patients’ behavior and the underlying cell biology. For the research aspect of her degree, she worked in a lab doing electrophysiology in rat hippocampal slices. Specifically, she discovered that adenosine—a nucleotide known to modulate cardiac rhythms—could play a neuroprotective role against oxidative stress, a situation in which reactive oxygen species accumulate faster than the body can get rid of them. When her PI suggested that she publish her results, Cláudia was surprised and thrilled. She was proud that she had produced something that others in the field might want to read.  

While she liked electrophysiology, Cláudia knew that for her next scientific adventure, she wanted to dive deeper into cellular function at a smaller scale. With limited options to stay in Portugal to pursue cellular neuroscience, and with an eagerness to experience life abroad, Cláudia applied for and received a national fellowship that would allow her to do PhD research anywhere in the world. She chose to work in a relatively new lab led by Dr. Gunnar Gouras at Weill Cornell Medical College in New York. While she had also considered more established labs, she clicked with Gunnar and was drawn to one of the big questions his lab was trying to answer: how do the pathological hallmarks of Alzheimer’s disease (AD) affect the brain at a molecular level?

AD is characterized by an accumulation of two proteins, one of which is beta-amyloid (Aβ). Aβ can misfold and aggregate into extracellular “plaques” thought to interrupt neuronal communication. However, the Gouras lab had also noticed Aβ inside neurons in plaque-less brain regions in brains from AD patients, animal models of AD, and even in healthy mice and rats. Interestingly, the Aβ was often inside endosomes, organelles involved in trafficking proteins and lipids to different subcellular components. Why was it there? How was this affecting the neurons? Cláudia noticed that whenever she saw Aβ inside neurons, their synapse morphology did not look right. She discovered that when she cultured these Aβ-burdened neurons for 19 days, they underwent synapse loss, and clearing the Aβ did not reverse this loss. However, when she looked at an earlier timepoint to pinpoint the cause of synapse loss, she found that, after 12 days in culture, postsynaptic cells had fewer glutamate receptors. Glutamate receptors allow neurons to respond to signals from other neurons, and a change in their number thus reflects a change in neurons’ responsivity. Remarkably, at this earlier stage, blocking Aβ was able to reverse the pathology and prevent synapse loss. Ultimately, Cláudia discovered that Aβ accumulation inside neurons was disrupting the trafficking, recycling, and degradation of synaptic proteins. 

While Cláudia was nearing the end of her PhD, her husband was searching for faculty positions. He accepted a job in Paris, so when it was time for Cláudia to apply for a postdoc, she focused her search in Paris. She chose to work with Dr. Evelyne Coudrier, a PI within the greater cellular biology lab of Dr. Daniel Louvard at Institut Curie. While joining this lab meant stepping away from neuroscience, Cláudia took this opportunity to further explore her interest in cellular mechanisms, with the goal of ultimately using this knowledge to study neurons in her future lab. The Coudrier lab was studying the role of myosin in endosomes. Myosin is responsible for connecting the actin cytoskeleton to endosomes and exerting force to deform the membrane, a process necessary for certain endosomal functions. Cláudia set out to determine how endosomes might be altered in cells without myosin 1b. For six months she searched desperately for an endosomal phenotype in cells lacking myosin 1b, to no avail. However, in her imaging, she noticed the Golgi (a different organelle) in the cells lacking myosin 1b often looked strangely compact. With her imposter syndrome in full swing, Cláudia half convinced herself that she was imagining it. She brought in her husband for a second opinion. After looking at the images, her husband, a cellular biologist himself, shouted, “You have a phenotype!” Her PI agreed, and Cláudia left the endosome behind to focus on the Golgi. She ultimately discovered a previously unknown role for myosin in the trans-Golgi network: myosin is required for Golgi membrane deformation before proteins can leave the Golgi towards their final destination. These findings allowed her to publish the big paper she felt she needed for securing an independent position. 

Cláudia, always bent on studying the questions she found most interesting, felt that being a PI would be the best way to continue asking and answering these scientific questions. However, the faculty job search was a challenging time. Having given birth to her second son 10 days after finishing her postdoc, Cláudia found it difficult to switch off “mom mode” and concentrate on formulating a plan for her independent lab. She pushed through, however, and applied to several opportunities, focusing on Paris and Portugal. In the case of the latter, Cláudia harbored an idealistic idea of returning to Portugal and using the education and training she had obtained abroad to promote scientific progress back home. After visiting various institutions, Cláudia felt that the NOVA Medical School in Lisbon was a particularly great fit. She applied for two grants, one from the Portuguese government and one from the European Commission, to fund her salary and her lab. But as time dragged on with no promising options and silence on the grant front, Cláudia decided to apply to industry jobs and other opportunities. She landed a position as project manager with the International Rare Diseases Research Consortium at Inserm (the French equivalent of the NIH). She was excited about the work and the prospect of learning something new. Then, two months into her new job, she heard that she had received both grants. And that was that. Cláudia moved to Portugal to start her lab at NOVA. 

In her new lab, Cláudia has combined her interest in AD, her expertise in cellular biology, and new human genetics data to create a research program on how aging and genetic risk factors contribute to synaptic dysfunction in AD. The lab has discovered that some genetic risk factors for AD in fact disrupt endosomal trafficking in neurons, increasing the production of Aβ in endosomes. Their work suggests that the driving pathology in AD might be dysfunction of the endosomal and lysosomal trafficking systems, a paradigm shift in the way that the field thinks about the disease. While leading this research was second nature to Cláudia, managing a team was something she had to learn. At first, she tried teaching her trainees how she works, but in the end came to realize it was more effective to teach them how to figure out how they work best. Cláudia has found this evolution particularly rewarding, and she has found further gratification in teaching undergrads and master’s students. She loves having the opportunity to change how young students think about science and research. Undoubtedly, many of these students will come away with Cláudia’s unbridled excitement for scientific discovery.

Find out more about Cláudia and her lab’s research here.

Listen to Margarida’s full interview with Cláudia on November 5, 2022 below!