The first Monday of each month, the Knight Initiative for Brain Resilience will host monthly seminars to bring together awardees, affiliated professors and students for a series of 'lab meeting' styled talks. Two speakers will discuss their brain resilience research, experiences in the field, and answer questions about their work.
To support our researchers' participation in this open science ‘lab-meeting style’ exchange of ideas, these seminars are not streamed/recorded and are only open to members of the Stanford community.
Jacob Simon, Stanford University
A novel toolset for understanding neuromodulation
As a postdoctoral scholar, I am working to better understand the role of neuromodulation in brain function. A major challenge in studying neuromodulation is the high degree of multiplexing as many genomes, including both fruit flies and humans, encode hundreds of orthogonal modulators and receptors. To address this subject, I take advantage of the relatively well-studied fruit fly visual system, where we have access to connectomic, gene expression, and functional data for many cell types. Despite the dense expression of neuromodulator receptors, relatively little is known about the role of neuromodulation in vision. I am developing a novel toolset, constitutively-active engineered phosphodiesterases, to perturb key intracellular signaling pathways downstream of neuromodulator receptors in order to better understand their function in vivo. After validating this tool in the fruit fly visual system, I hope to extend this approach to better understand sleep. Despite the dramatic effects of sleep disruption on brain function, relatively little is known about either the physiological functions of sleep or how the sleep state is regulated. Answers to these questions will ultimately lead to new approaches for improving sleep quality and brain resilience.
Joe Winer, Stanford University
Effects of ⍺-synuclein pathology in normal aging and Alzheimer’s disease
Parkinson’s disease and dementia with Lewy bodies, neurodegenerative syndromes collectively referred to as Lewy body disease, are pathologically characterized by the intraneuronal aggregation of misfolded α-synuclein. ⍺-synuclein is also commonly observed in the context of Alzheimer’s disease and is estimated to be present in around 10% of asymptomatic older individuals. By leveraging the recently developed CSF ⍺-synuclein seed amplification assay, we determined ⍺-synuclein status in over 400 Stanford research participants across the aging and neurodegenerative disease spectrum. Our work investigates the frequency of ⍺-synuclein biomarker positivity in ⍺-synuclein positive clinically unimpaired individuals, as well as associations with demographics, other biomarkers, cognitive performance, and clinical outcomes. Our research has implications for understanding the biological and clinical progression of Lewy body disease, as well as early disease detection for clinical trials.