April Pruitt, 5th Year PhD Student at the Yale School of Medicine

Exploring the Genetics of Autism: April Pruitt's Journey in Neuroscience Research

WRITTEN by Myla Toliver

EDITED BY Ariana Martinez

Behind every devoted scientist is a story of incredible persistence, passion, and burning curiosity. April Pruitt, a fifth-year PhD student at the Yale School of Medicine is no exception. Growing up, April described herself as curious both inside and outside the classroom. She recalled how she valued learning especially in religious contexts. She has always been heavily involved in the Catholic church–devoting herself to lifelong learning of her religion. April described her faith as the part of her identity she takes the most pride in. Her love for learning doesn’t end there. April has trained in various styles of dance, including ballet, jazz, modern, lyrical, and contemporary. She has even continued her dance into her adult and graduate student life, where she has often performed in the Yale Dance Works group. April emphasized the importance of still pursuing other interests while getting her doctorate. She has also developed a strong passion for music and singing, frequently participating in her church choir. April also enjoys visiting museums so much that she was motivated to serve as an assistant curator for the neuroscience exhibit Mind Over Matter at the Peabody Museum, another example of her exceptional passion for learning. April's journey into sciences began in the fourth grade, when her youthful curiosity, paired with her desire to copy the scientific endeavors of her older siblings, inspired her to compete in her school's science fairs. These early learning experiences built the foundation for her later curiosities.

April's first formal research experience began during her undergraduate years at the University of Louisiana at Lafayette in preparation to complete her pre-medical requirements. She majored in biology with minors in chemistry and psychology, a combination not dissimilar to neuroscience. Her first lab experience was in a phytoplankton ecology lab under the mentorship of Dr. Beth Stauffer, where she studied how dinoflagellates, tiny organisms in estuaries, recover from drastic changes in salinity, quite literally "testing out the waters" of advanced research. This involved fieldwork in the Gulf of Mexico and lab analysis of seawater samples to understand these organisms' resilience to environmental changes. While the study wasn't focused on medical sciences, it gave April invaluable exposure to research practices. In a summer undergraduate research program at Stanford University, April worked in a stem cell lab studying a copy number variant (16p11.2) linked to autism. This mutation, which results in the deletion of 29 genes, is associated with an enlarged brain and intellectual disability in children. Her work involved growing patient-derived stem cells and neural progenitor cells to study proliferation rates at different stages of development. April's connection to a high school teacher who had two sons with varying conditions of autism further motivated her interest in her studies. Because autism is a complex disorder, each individual exhibits traits different from the next, which makes the research of its mechanisms both challenging and rewarding. This combination of meaningful research and a deep personal connection to autism further redirected April to a career devoted to science.

"The only things you need to be a scientist are curiosity, creativity, and resilience; everything else you can learn."

Her research focuses on understanding the genetic and molecular mechanisms of autism spectrum disorder (ASD) through genomics. She strives to discover what specific genes are associated with ASD and what their influence is on the brain. Her approach includes disrupting genes (mainly through loss-of-function mutations) and examining the effects on gene expression, molecular pathways, and protein interactions. She also investigates neural activity, focusing on how neurons communicate and how these processes are affected by ASD-related genes. A key aspect of her research involves exploring how these ASD-related genes impact synaptic signaling and ion channel function in the brain. The ultimate goal is to identify converging molecular mechanisms across the more than 200 genes associated with ASD despite the complexity of their interactions, which vary based on context (such as brain activity and gene expression).

April also works in drug screening to find treatments that may one day reduce some of the symptoms of ASD like hypersensitivity and sleep problems. Her lab tests a variety of drugs to assess their potential to reverse dysregulated pathways and improve brain function, ultimately aiming to enhance the quality of life for individuals with ASD. In addition, April explores sex differences in ASD, which is more commonly diagnosed in males. Her work examines the role of estrogen in early brain development, testing whether this hormone could act as a protective factor that might help explain the sex bias in ASD. She hypothesizes that females require a more significant genetic burden to develop ASD and that estrogen might help mitigate some of the developmental disruptions caused by genetic mutations associated with the disorder.

When asked what advice she would provide aspiring scientists, April emphasized the importance of investing time in learning about the hard sciences and the humanities or social sciences. She believes that an interdisciplinary thought process, combined with empathy and an understanding of the human condition, skills that are often gained with exposure to a humanities education, can enhance scientific research. These skills help scientists relate to people and ensure that science is accessible and understandable to individuals who are not specialists in this field.  April emphasized the value of creativity and curiosity in graduate school. She explained that while undergraduate education often focuses on absorbing and memorizing knowledge, earning a PhD requires transitioning to making new discoveries. When I asked April if she had any advice for undergraduates interested in PhD or doctorate programs April explained the importance of exploring a diverse range of interests. Finally, she recommends students explore diverse subjects to discover their true interests and motivations, as passion for the subject is crucial for perseverance in graduate school. April Pruitt is a true example of an investigator and changemaker.