Leveraging single-cell multiomics to understand neurodegenerative disease risk
MSOB Room X303
Abstract: Broadly speaking, we aim to understand one question– why do some individuals develop disease while others remain resilient? As part of the Gladstone Institute of Neurological Disease, our research primarily focuses on Alzheimer’s and Parkinson’s diseases with collaborative projects on other neurological diseases such as traumatic brain injury and stroke. We are particularly interested in the noncoding genome and how noncoding genetic variation plays a role in complex disease. We combine large-scale single-cell data sets generated from postmortem human brain with machine learning paradigms for the prediction of variant-to-function biology. In addition to working towards a better understanding of the molecular and genetic underpinnings of neurodegenerative disease, the lab is also deeply engaged in the development of open-source analytical software for the analysis of single-cell data. This talk wi l span the ful breadth of our research platform, including discussion of a recent tool for single-cell clustering called CHOIR, and our unpublished work investigating the role of rare noncoding variants in disease.
Bio: Ryan started his scientific career at Princeton University where he graduated with a focus in Molecular Biology and Computer Science. Ryan's thesis work at Stanford University in the laboratory of Dr. Ravi Majeti centered on the genetic evolution of acute myeloid leukemia where he demonstrated that the earliest mutations that occur in acute myeloid leukemia affect genes that regulate the epigenome. Following this line of study, Ryan began his postdoctoral work in the laboratory of Dr. Howard Chang studying epigenetics in human disease. This work eventually led Ryan to a collaboration with Dr. Thomas Montine which refocused his interests to study neurological disease. Ryan joined the Gladstone Institute of Neurological Disease in July, 2020 to study the contributions of genetic and non-genetic factors to neurodegenerative diseases. Using computational biology, large-scale screens, and single-cel technologies, Ryan's laboratory probes the epigenome of cells derived from patients, with the aim to understand how it impacts disease risk and to develop novel avenues for therapeutic interventions.
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