PiN Faculty Member - Steven McCarroll, PhD

Steven McCarroll, PhD

Professor of Genetics

Harvard Medical School
NRB 260
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-7794
Fax: 617-432-6306
Visit my lab page here.

We are interested in understanding how human genome variation influences the molecular biology of neurons, microglia, and other cell populations in the brain, on its way to shaping brain phenotypes such as schizophrenia and bipolar disorder. In human populations, rare and common genetic variations affect the cell-type-specific expression patterns and precise protein sequences of almost all human genes. This reservoir of natural genetic variation offers a powerful tool for discovering genetic influences on the molecular biology of neurons and other cells, and for learning about the pathogenesis of neuropsychiatric illness and other human diseases. We are using human genetics and genomics to begin to ascertain molecular influences on these neuropsychiatric disorders, then developing experimental systems to understand how these genetic perturbations affect the molecular biology of neurons and other cells. Our approaches include the following.

Human genetics. Scientists in the lab have developed many molecular tools and statistical approaches for better ascertaining human genome variation and relating it to genetically complex phenotypes. We use human genetics to find genes and alleles that shape people's risk for schizophrenia and bipolar disorder. We analyze genomic DNA from large cohorts of patients with schizophrenia and bipolar disorder, to discover rare and common genetic variation that shapes risk of disease in human populations. Such studies are providing early insight into the molecular components of these disorders, strongly implicating synaptic dysfunction in their etiology.

Single-cell expression. We have been developing technology with which we can simultaneously analyze the transcriptomes (global RNA expression patterns) of thousands of individual cells. We are beginning to use this approach to study brain regions at the levels of (i) all of the cell types that are present; and (ii) the biological states that those cells assume under a variety of conditions. Our goals include to develop systematic, inductive ways – informed by genomescale data – to classify all of the cells that are present in brain regions and neuronal circuits; and to better understand human pathological samples and mouse models of human disease. We hope in this way to more deeply learn from the genetic perturbations that our genetic studies have implicated in schizophrenia and bipolar disorder: in what cell populations do these genetic perturbations act, and how do they alter the biological states of these cells?

Genomic study of the interactions between neurons and microglia. We study the ways in which neurons and microglia interact with one another, using coculture systems that we perturb and analyze at genetic, genomic, and other levels.

Our goal is to identify the key molecular events in the development of schizophrenia and bipolar disorder, and the relationship of these events to normal brain
function and development.

Last Update: 9/16/2020


For a complete listing of publications click here.



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