My name is Blaine Weiss, and I am a graduate student in the department of pharmacology and nutritional sciences in the lab of Christopher Norris, PhD. Our group studies the role of astrocyte reactivity in contributing to the progression of Alzheimer’s disease.
My family moved to Lexington from Tampa in 2003 and quickly fell in love with the natural beauty of Kentucky. I graduated from Tates Creek High School before beginning my undergraduate education at UK. I began my career at Sanders-Brown in 2015 and was hired as a technician upon graduation. I was encouraged by Dr. Norris to enter the graduate program in 2021. Over the past nine years, I contributed to several studies around the center, and have had an incredibly rewarding start to my career.
My inspiration to pursue medical science began with my parents, who lost their parents to Parkinson's and Alzheimer's disease. This motivation grew further when I started working as a technician, where I was inspired by the innovative dementia research at Sanders-Brown. Growing up, I was fascinated with building models and mechanical toys and wanted to learn how things work. In the center, Dr. Norris fostered my curiosity by allowing me to participate in the assembly of lab equipment, and helped me develop technical skills to prepare me for future endeavors in scientific research. At the beginning of my graduate work, he challenged me further to develop new techniques that could address specific questions surrounding brain function.
Our recent work focuses on how cerebral amyloid impacts astrocyte and cerebrovascular function. Astrocytes play an essential role in synaptic function, brain metabolism, cerebral blood flow, and blood-brain barrier integrity—all of which are compromised in Alzheimer's disease. However, the exact mechanisms behind these impairments have been an ongoing question in the field. In the lab, we use Two-Photon microscopy to observe these functions from awake mice in real-time. To analyze the relationships between astrocyte activity and brain function, I developed several software packages that analyze video and raw signal data, for feature and pattern recognition, spatial statistics, and data visualization.
Since beginning in my graduate program, I have had the privilege of presenting this work at 10 regional and international conferences. In July, I was awarded the Alzheimer’s Association International Conference Fellowship Award to present my project results in Philadelphia. More recently, I was honored with an Outstanding Poster Award at the 2024 Markesbery Symposium, where I shared the latest findings of our study.
This work contributes an in-depth characterization of the signaling activity from astrocytes in intact, awake animals, and reveals changes in the relationships between them, neuronal activity, and regulation of cerebral blood flow in Alzheimer’s like disease states. Our findings describe an overall weakening of astrocyte physiology, from diminished signal strength to a disconnection of their networks. Notably, the study also highlights the mechanistic role of astrocyte signaling in neurovascular coupling and reveals a complete uncoupling of astrocyte signals from stimulation-induced vasoreactivity in the presence of moderate amyloid accumulation. These insights have been invaluable for understanding functional astrocyte reactivity, but many questions remain.
Our ongoing and future experiments aim to directly target astrocyte activity to rescue these functional impairments. This includes restoring protective glutamate transporters to reduce excitotoxicity, regulating metabolism, re-establishing calcium homeostasis, and protecting vascular integrity and function. I’m excited to continue this work, hopeful that we will advance knowledge about brain health that will support the development of future therapies. I’m grateful for the support I’ve received at Sanders-Brown, and look forward to what lies ahead!