Dr.  Aleksandra Badura

Dr. Aleksandra Badura

 

Associate Professor, Erasmus MC, Netherlands
Postdoctoral Fellow Princeton University
PhD Erasmus MC, Netherlands

Dr. Aleksandra Badura’s interest in neuroscience took root during her undergraduate studies at the Jagiellonian University in Krakow, Poland. Initially set on pursuing a career in business psychology, her experience having vivid dreams led her to choose to study neuropsychology for her undergraduate thesis. Encouraged by her thesis advisor, she applied for and received a scholarship to study the neuroscience of sleep abroad in the Netherlands. With a leap of faith, Aleksandra embarked on her first flight and landed in a world of scientific wonder. In this research lab, Aleksandra placed EEG electrodes on rats and scored their sleep behavior while observing their brain activity. When she saw brain waves shifting in sync with behavior, she was captivated. Now, as an Associate Professor at the Department of Neuroscience at Erasmus University in Rotterdam, Netherlands, she leads an ambitious research program investigating the cerebellum’s role in neurodevelopmental disorders, particularly autism spectrum disorder (ASD). Her lab focuses on understanding how disruptions to cerebellar circuits during critical developmental windows can lead to lasting cognitive and social impairments.

Following her initial work with EEG, Aleksandra sought to transition from examining overall brain wave patterns to understanding the actions of single neurons during animal behavior. This led her to pursue a PhD in Neuroscience at Erasmus University in Rotterdam, joining Dr. Chris De Zeeuw's lab to study motor control in the cerebellum. Purkinje cells in the cerebellum help coordinate movement by balancing two types of signals: complex spikes driven by powerful direct synapses from climbing fibers, and simple spikes indirectly driven by mossy fiber pathways. Climbing fibers typically cross from one side of the brainstem to the opposite cerebellar hemisphere to form these synapses, while mossy fibers remain on the same side, relaying their distributed input through granule cells and their parallel fibers. Typically, complex and simple spikes display a reciprocal firing pattern—when the frequency of one increases, the other decreases. This reciprocity is crucial for motor learning and coordination, but at the time, how this reciprocity was accomplished was not understood. In her PhD, Aleksandra used a transgenic mouse line to rewire the cerebellum so that climbing fibers projected to the same hemisphere, instead of crossing over as usual. After rerouting these neurons, Aleksandra observed a disruption of the reciprocal firing pattern in the cerebellum and a profound ataxic phenotype of the mice. In essence, her work demonstrated that climbing fiber input is crucial for maintaining the precise spike timing needed for smooth movement. Aleksandra recalls being shocked when she first observed the disruption in the cerebellar firing patterns, running to her PI’s office exclaiming “you have to see this! It’s unbelievable!” Her groundbreaking findings were published in Neuron in 2013.

For her postdoc, Aleksandra sought out a research project with more translational relevance. Inspired by the clinical findings that cerebral damage in infants significantly increased the risk of autism, she joined Prof. Samuel Wang's lab at Princeton University and pursued a project of her own design. She set out to investigate how early-life perturbation of cerebellar circuits impact the development of social behavior and behavioral flexibility, particularly in the context of ASD. To precisely control interneurons in the molecular layer of the mouse cerebellar cortex during key stages of development, Aleksandra employed a chemogenetic tool called DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). By introducing DREADDs, she could activate or inhibit these interneurons, allowing for targeted disruption of cerebellar function. Using this tool in combination with two-photon imaging, Aleksandra found that selectively inhibiting the molecular layer interneurons in juveniles—during a critical period for the development of behaviors like social preference and flexible learning—led to lasting deficits in these abilities, providing insights into how early cerebellar dysfunction may contribute to ASD. These findings fundamentally changed how we understand the function of the cerebellum in cognitive and social development. 

After a couple of years in her first postdoc, Aleksandra received a Veni ZonMw postdoctoral grant, which prompted her to move to the Netherlands Institute for Neuroscience in Amsterdam for a second postdoctoral position. Here she continued studying the relationship between ASD and cerebellar function, while also remaining a Visiting Research Collaborator at Princeton Neuroscience Institute. Running long experiments and putting in 60+ hour long work weeks, Aleksandra was beginning to feel the effects of burnout. Balancing the work of two parallel postdocs in two different time zones and neglecting her mental health pushed her past her limits. Aleksandra approached her supervisor, tearfully telling him that she wanted to quit. He said to her, “I will consider it one of my biggest professional failures if you quit,” and asked what he could do to keep her there. Together they made a plan. Aleksandra took time off and three months later returned to the lab with the goal of conducting research in a more sustainable way. Bolstering herself with a healthier work/life balance and knowing that she had a supportive mentor in her corner helped Aleksandra cross the finish line and land a tenure track position in the Department of Neuroscience at Erasmus University.

Aleksandra’s transition to becoming a Principal Investigator was not without its challenges. She realized that the job is far more about conducting business than conducting science. “I thought I was ready,” she recalls. “Then [I started my] lab, and I was like—oh my god, I’m so not ready.” Overnight, Aleksandra became a manager, an accountant, an HR department, and a procurement officer, all while trying to establish her research program. Taking a leadership course assisted her in managing this steep learning curve. She also looked to her friends and fellow new female PIs for advice and support. As a result, her lab is now flourishing.

The Badura lab broadly studies the neural networks underlying behavioral flexibility. They aim to understand how cerebello-cortical brain activity influences adaptive behavior and how this circuitry underlies maladaptive repetitive behaviors, a common characteristic of ASD. By integrating in vivo electrophysiology, calcium imaging, virtual reality, and longitudinal behavior monitoring, Aleksandra’s lab seeks to uncover the neural mechanisms driving these behaviors in mouse models of ASD. She also has extensive collaborations with clinicians and societal partners to ensure that results of her studies can be useful in a clinical setting. Currently, they aim to understand how sex differences and genetic and environmental risk factors (such as early brain damage) influence cerebellar function in ASD. A second branch of the lab is exploring how primary immunodeficiency leads to risk for neurodevelopmental disorders and ASD. Ultimately, Aleksandra hopes to identify mechanisms that can be used as early diagnostic strategies for ASD.

Aleksandra is dedicated to fostering a lab environment built on teamwork and thoughtful mentorship. During her first postdoc, she experienced firsthand the power of collaborative science while working closely with PhD and undergraduate students. Aware that science moves rapidly and that the importance of individual studies may fade over time, she views her true legacy not in citations but in the people she mentors. Her mentees carry forward the skills, mindset, and lessons from her lab, shaping future discoveries even if they leave science. Reflecting on her journey—from being a psychology student in Poland to a leading neuroscientist in the Netherlands—Aleksandra has come to view science as a shared pursuit of discovery. Driven by curiosity, perseverance, and collaboration, she believes the most impactful breakthroughs stem from collective passion, rather than individual efforts, to push the boundaries of knowledge.

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

Listen to Margarida’s full interview with Aleksandra on December 12, 2024 below!

 
Dr. Malú Tansey

Dr. Malú Tansey