Boston University School of Medicine, Center for Regenerative Medicine, Boston, MA
The Center for Regenerative Medicine (CReM), a department of the Boston University (BU) School of Medicine, is a collaborative unit composed of seven labs. This summer, I worked under Dr. Angie Serrano, conducting an independent bioinformatic analysis research project to study Kabuki Syndrome I (KSI), a rare congenital syndrome caused by pathogenic variants in the histone methyltransferase KMT2D. KSI patients present neurodevelopmental disorders often accompanied by microcephaly.
Previously, our lab conducted snATACseq, which identified open chromatin regions matching the VAV1 oncogene in KMT2D-/- hiPSC cells. The goal of my independent summer project was to assess the implications of VAV1 during neurogenesis and to determine whether the Vav GEF signaling pathway was altered in KMT2D-/- hiPSC-derived brain organoids.
With no previous experience in bioinformatics, I learned how to interpret and write code in R to conduct scRNAseq. I used Seurat, DESeq and GSEA packages in R Studio to examine Vav signaling in one-month-old cortical brain organoids. Little is known about how VAV1 relates to neurogenesis, so I proposed a completely new Vav signaling pathway to explain this relationship. I’ll be presenting my project at the BU Evans Day research conference this fall.
My scRNAseq analysis revealed that while VAV1 is not directly expressed in one-month-old cortical organoids, its downstream genes show expression patterns indicative of oligodendrocyte prematuration in KMT2D-/- organoids, a finding that has never been established before.
Beyond learning how to manage the immense responsibility of designing and conducting an independent research project about the previously unexplored link between VAV1 and KSI, I was immersed in a dynamic community of researchers, medical students and physicians. I had the opportunity to talk to people at every stage of the pathway to becoming a doctor. I worked alongside MD and MD/Ph.D. students, who inspired me to start a scientific journal club for this coming school year. I talked to medical residents on the bus I took to and from the lab, who described their experiences in patient care. I attended weekly meetings with my PI and other researchers in my lab, and I had the opportunity to talk to the chief of neurosurgery at the Boston Medical Center. Since age 12, I have aspired to become a neurosurgeon, and meeting with these professionals further confirmed my interest in neurosurgery and neuroscience. It often seems as though there is only one pathway to becoming a doctor; however, each of these students and professionals took a different path. That lesson was perhaps one of the most important I learned this summer, as it can be easy to get caught up in the pressure to rush into a career without appreciating the journey it takes to get there.
This summer, I was able to experience what it felt like to contribute something meaningful to scientific research, and I had the opportunity to work alongside highly respected researchers and doctors. I would like to express my gratitude for the ’68 Center and the BU CReM for supporting me throughout this transformative experience.