Michael Oldham, PhD

Asst Professor in Residence
M_NeuSrg-General
+1 415 502-5498

The overarching goal of research in the Oldham lab is to understand the molecular basis of cellular identity in the human brain in health and disease, with a particular emphasis on glioma.  In pursuit of this goal we are developing new ways of studying biological systems that combine standardized sampling strategies, multiomic data collection, and multivariate analytical methods. 

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 gene coexpression relationships over thousands of heterogeneous tissue samples, it is possible to isolate reproducible transcriptional signatures of distinct cell types and cellular processes in silico.

The engine of the lab is an in-house 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.

Projects in the lab are organized around studies of glioma and other brain cancers, normal human brain, and developing human brain:

1) Understanding the most predictable transcriptional consequences of recurrent mutations that cause glioma (in particular, low-grade glioma) to identify novel therapeutic targets;

2) Developing quantitative definitions of cell types in the neurotypical adult human brain based on integrative gene coexpression analysis;

3) Determining the molecular characteristics of neural stem cells and their progeny in the developing human brain and how these compare with other species and the adult human brain.

Participation in these projects generally ensures that lab members are fluent (or develop fluency) in computational and experimental research strategies.

Primary Thematic Area: 
Neurobiology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Decoding the molecular basis of cellular identity in the human brain

Websites

Featured Publications: 

Transcriptional architecture of the human brain.

Nature neuroscience

Kelley KW, Oldham MC

Radial glia require PDGFD-PDGFRß signalling in human but not mouse neocortex.

Nature

Lui JH, Nowakowski TJ, Pollen AA, Javaherian A, Kriegstein AR, Oldham MC

Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions.

Glia

Molofsky AV, Glasgow SM, Chaboub LS, Tsai HH, Murnen AT, Kelley KW, Fancy SP, Yuen TJ, Madireddy L, Baranzini S, Deneen B, Rowitch DH, Oldham MC

Functional organization of the transcriptome in human brain.

Nature neuroscience

Oldham MC, Konopka G, Iwamoto K, Langfelder P, Kato T, Horvath S, Geschwind DH