ECU researcher receives $1.2 million brain research grant, career achievement honors

An East Carolina University researcher has earned a National Science Foundation Career Award for $1.2 million over five years to study synapse formation in brain development, which is vital to cognitive processes like learning and memory.

Dr. Karen Litwa, assistant professor in the Brody School of Medicine’s Department of Anatomy and Cell Biology, was awarded the grant for the project, which aims to address how synapses — the points of contact between neurons where information is passed from one neuron to the next — form in brain development and mediate the transfer of information in the brain.

The research techniques will allow “unrivaled experimental access to developing synapses,” according to Litwa’s project abstract.

“The brain supports complex cognitive processes, such as learning and memory,” Litwa said. “These complex processes require information transfer within the brain. Synapses mediate this information transfer, yet important details about the exact ways that synapses form in brain development are still unknown.”

Each year, close to 500 researchers are recognized for their potential to serve as “academic role models in research and education and to lead advances in the mission of their department or organization,” according to the NSF.

Litwa’s research has long focused on brain development and how it impacts health, including growing "mini-brains" to better understand neurological conditions like autism.

Litwa’s research has long focused on brain development and how it impacts health, including growing “mini-brains” to better understand neurological conditions like autism.

“Dr. Litwa joined this elite group and has shown that ECU’s investments in growing the university’s research portfolio are paying off, and we are thrilled that she has achieved this prestigious award,” said Dr. Sharon Paynter, ECU’s acting chief research and engagement officer. “This award is a signal of the high-quality research undertaken at ECU. It also evidences the return on our investments in recruiting innovative faculty and providing them with institutional research support once they are on campus. The NSF Career award will allow Dr. Litwa to engage and inspire students to continue their own journeys of discovery.”

Litwa’s research will focus on discovering what the requirements are for pre- and post-synaptic compartments to initially adhere and what determines whether that adherence persists and matures. According to the project abstract, “the set of experiments will test the hypothesis that post-synaptic dendritic filopodia (small, membranous protrusions found primarily on branching stretches of developing neurons) promote synapse formation in developing neural circuits.”

To test the hypotheses, neurons will be co-cultured in microfluidic systems to isolate the contributions of pre- and post-synaptic compartments to synapse formation. CRISPR interference — a technique that allows the repression of gene expression — will be used to alter the expression of specific molecules either separately or in combination and assess the resulting impact to synapse formation with confocal and STORM microscopy — the most widely used super-resolution microscopy technique for single-molecule imaging — according to the abstract.

Fluorescent biosensors will be used to perturb and monitor filopodia-mediated signaling events. Synapse formation will be observed in live neuron cultures and fixed brain tissues.

This research will also compare regional differences between synapse formation in the hippocampus and cortex.

Discovering the brain’s secrets

Litwa’s research has long focused on brain development and how it impacts health. Her previous studies have included growing human cortical spheroids, or “mini-brains,” to better understand neurological conditions like autism. Her work has earned her a reputation as a “brain builder.”

“Our lab has a long-standing interest in the developing brain. I consider myself a cellular construction worker because I am interested in how the brain builds connections between neurons,” Litwa said. “I use a variety of techniques to visualize and manipulate synapse building.”

Her latest endeavor builds on some of her lab’s previous discoveries.

“In this new project, we are researching the foundations of synapse building,” she said. “In spite of the critical importance of synapses for brain function, we still don’t know the precise mechanisms by which synapses form in the developing brain. I am hoping that my work will begin to fill in some of these gaps in our knowledge.”

The award has far-reaching implications for Litwa, including setting a strong foundation for other labs to build upon.

“Other research labs will also benefit from these insights,” she said. “In some of our other research, we address how genetic mutations and environmental factors alter the mechanisms of synapse formation in neurodevelopmental disorders.”

Litwa's project will include the development of a microscopy course for undergraduates to learn advanced techniques and to gain exposure to highly detailed imagery.

Litwa’s project will include the development of a microscopy course for undergraduates to learn advanced techniques and to gain exposure to highly detailed imagery.

She is also humbled by the Career Award from the NSF, seeing it as a nod to the contributions and future discoveries her work could provide in the field.

“It means that my colleagues at the national level recognize the value of my research and teaching,” she said. “At a personal level, I get to continue to do what I love. I also get to expand my research program to include more individuals at different levels of scientific training.”

Testing scientific boundaries

Litwa’s own educational experiences angled her perspective of opportunity and discovery and caused her to question the limits of possibility.

“I am a first-generation college graduate,” she said. “I have always been curious, creative and a lover of detail. I found my passion for science when I realized that I could have a career asking questions and finding ways to answer them.”

During a summer undergraduate research experience at the University of Pittsburgh, Litwa became fascinated with the beauty and simplicity of the single cell eukaryote, baker’s yeast.

“When I realized how little we understood about yeast, it gave me a better appreciation for how many mysteries were yet to be explored in biology and motivated me to pursue a career in scientific research,” she said. “I have been fortunate to continue to explore biological mysteries since my first research experience with yeast. I am also extremely grateful for the amazing scientists who have shared this research journey with me.”

It was Litwa’s Ph.D. studies at Emory University that led to her love of the brain. She began to study synapses and continued that exploration in postdoctoral research at the University of Virginia. There, she developed her own research using “mini-brains” and investigated new ideas and technologies through which she and her lab could contribute new knowledge and material.

“As a first-generation college graduate and woman in science, I believe that education is key to introducing diverse individuals to science. Without amazing educators and mentors, I would not have been exposed to academic research and taught the skills necessary to be a successful researcher,” Litwa said.

She hopes her instructional style leads other young scientists beyond the beaten path.

“Through my educational activities, such as the microscopy course, I hope to share my passion for research with a future generation of scientists. Students in my microscopy class are actually conducting research that contributes to our understanding of synapse building in brain development,” she said. “And even if my teaching doesn’t spark a passion for research in them, I hope that it will at least give them an appreciation for the importance of biological research and equip them with skills that advance their careers. Since microscopy allows them to view the beauty of neurons, I hope it sparks both wonder and a desire for continued exploration.”

‘Citizen of the university’

Litwa can build on that sentiment through the NSF grant, which includes educational components that could open doors to the world of science for students from kindergarten to graduate-level work.

The project will include the development of a microscopy course for undergraduates to learn advanced techniques and to gain exposure to highly detailed imagery that yields both scientific and aesthetic benefits. The images will be publicly displayed in the community, laying the groundwork for art as a medium to teach schoolchildren about scientific concepts.

“This project will cultivate student and community science appreciation and interest, while also equipping a future generation of scientists with the knowledge and technical skills to tackle difficult biological questions,” Litwa said.

High school, undergraduate and graduate students will also engage in a variety of scientific disciplines, from neuroscience to stem cell biology, she added.

“By integrating this research with scientific outreach and educational activities, this project will also increase research opportunities for high school, undergraduate and graduate students,” according to the project abstract.

With the potential for the project to impact researchers and learners at many levels, Litwa said having the opportunity to embark on the new research at ECU is another facet of a rich campus experience. Litwa holds adjunct appointments in the Thomas Harriot College of Arts and Sciences’ departments of biology and psychology. She also is a part of a female faculty group on campus that supports her research and career development, as well as vice president of the Brody Women Faculty Committee; president of the Eastern Carolina Chapter of the Society for Neuroscience; co-chair of the Laser Technologies Application Group and faculty member of the Eastern Carolina Diabetes and Obesity Institute.

I consider myself a citizen of the university,” she said, adding that each of her ECU affiliations has contributed vital collaborations, expertise and feedback that have influenced her work and findings over the years.

“I am extremely grateful to the support that I have received and continue to receive from ECU for my research efforts. When I came to ECU, I received generous financial support to start my research program,” Litwa said. “I have also benefitted immensely from the scientific community across the ECU campus. This funded grant is evidence of the amazing research community at ECU.”