The overarching goal of research in the Oldham lab is to understand the molecular basis of cellular identity in the human brain. The human brain is an extraordinarily complex, heterogeneous structure, comprised of diverse cell types whose molecular and functional identities are poorly understood. Because gene expression lies at the root of cellular identity, much of our work is focused on understanding the organization of the human brain transcriptome. Our work is motivated by a simple but powerful idea: by analyzing the covariance structure of gene expression in the human brain, it is possible to isolate reproducible transcriptional signatures of distinct cell types and cellular processes in silico.
We are developing new ways of studying biological systems that combine standardized sampling strategies, multiomic data collection, and multivariate analytical methods. The engine of the lab is a custom computational pipeline for detecting patterns in omics datasets that is implemented in the R computing environment. Insights from computational analyses are used to generate hypotheses that are tested at the bench. Most of our work is focused on the analysis of human brain tissue and cells, but we also perform work in model systems when appropriate.