My name is Kristin Barbour, and I am a rising senior Biology major at Villanova University. Throughout my undergraduate career, I have participated in research under the mentorship and guidance of Dr. Dennis Wykoff (PhD). Dr. Wykoff’s lab aims to identify and characterize the gene promoters and transcription factors involved in the thiamine (Vitamin B1) biosynthesis pathway of Candida glabrata, a pathogenic yeast species. Thiamine is an essential nutrient for C. glabrata and, thus, interfering with the thiamine biosynthesis pathway provides a promising mechanism for novel antifungal therapeutics. This summer, I have had the remarkable opportunity to work in the lab of Dr. Evan Snyder (MD, PhD, FAAP) at the Sanford Consortium for Regenerative Medicine in La Jolla, California, under the direct guidance of Dr. Cameron Pernia (PhD). The Snyder lab utilizes stem cells as a platform to model complex neurological diseases by identifying and characterizing disease-specific hallmarks to develop novel diagnostic techniques and drug targets.

Neurodegenerative and psychiatric diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and bipolar disorder (BD) inflict a significant physical, emotional, and economic burden on individuals suffering from these diseases as well as on society as a whole. AD alone is the sixth leading cause of death in the US and costs the country an estimated $172 billion annually in health care related fees. Additionally, BD, which is hypothesized to be a neurodegenerative disease and is associated with higher risks of PD and AD, is the sixth leading cause of disability worldwide. Despite the deleterious impact precipitated by these neurodegenerative diseases, there is currently a lack of accurate diagnostic techniques that can effectively identify and distinguish between neurological diseases.

Previous work in the Snyder Lab revealed that neurons derived from individuals with BD have unique Calcium (Ca+2) regulation which can be visualized using Ca+2 imaging. Working in conjunction with SRF, the Snyder lab utilized abnormal neuronal Ca+2 kinetics as a disease-specific hallmark to develop a machine learning program for diagnosing BD. Over the course of my time in the Snyder lab, I have been working to explain this Ca+2 dysregulation at the genomic level using Whole Genome Sequencing (WGS) from mature BD neurons. I am also using this genomic analysis to establish a potential disease-specific genetic profile for BD neurons which could be used in tandem with Ca+2 imaging to further enhance the accuracy of novel BD diagnostic techniques. Additionally, I am utilizing the WGS results to identify genetic overlap between BD and the genetic risk loci previously associated with AD and PD. Discerning specific genetic alterations shared between AD, PD, and BD would provide insight into the specific molecular machinery and mechanisms involved in neurological diseases as well as neurodegradation itself, thus identifying potential drug targets for future therapeutic development.