Steven McCarroll, PhD, is the Dorothy and Milton Flier Associate Professor of Biomedical Sciences and Genetics at Harvard Medical School.
McCarroll's training has been broadly interdisciplinary with mentorship in many fields of science. He studied mathematics and economics as an undergraduate at Stanford University, doing research on industrial organization. McCarroll began working in molecular neuroscience with Dr. Cori Bargmann in 1997 and received his PhD in neuroscience from UC San Francisco for that work in 2004. He trained as a postdoctoral fellow in human genetics and genomics with Dr. David Altshuler, where his work revealed how genes and genomic segments commonly vary in copy number from person to person. He started his own lab at Harvard Medical School in 2009.
McCarroll and the scientists in his lab have developed many novel ways to use genomes and genome sequences to understand human biology and the molecular basis of disease. His lab has uncovered surprising ways in which genes and alelles shape risk of human diseases – from schizophrenia to cardiovascular illness to cancer.
Many of the discoveries from McCarroll's lab have involved unexpected insights arising from their new ways of analyzing genome sequences. For example, while studying DNA derived from people's blood samples, his lab discovered a common pre-cancerous state in which blood stem cells have acquired somatic mutations and then clonally expanded, creating a reservoir of pre-cancerous cells that greatly increases risk of developing cancer later in life. His lab also discovered that the human genome replicates (copies itself) in ways that vary from person to person and are shaped by inherited genetic variation.
McCarroll's lab developed technology (called "Drop-seq") that makes it possible to analyze how thousands of individual cells in complex tissues are using their genomes. Even before publishing the technology in Cell, they wrote detailed online protocols for doing Drop-seq experiments and analyzing the resulting data. Their protocols have been downloaded some 40,000 times and are being implemented in labs around the world to discover how genes shape the biology of organs and cellular systems.
Today McCarroll's most intense area of focus is to use genetics and genomics to reveal the biological basis of mental illness, in order to create a strong scientific foundation for developing next-generation therapies. In addition to serving as Director of Genetics for the Broad Institute's Stanley Center for Psychiatric Research, his laboratory at HMS is working to identify the biological mechanisms by which genes and alleles shape brain illnesses. Last year his lab made a major discovery, published in Nature, that the human genome's largest influence on risk of schizophrenia arises from alleles of the complement component 4 (C4) gene that shape the developmental process of cortical maturation and synaptic pruning that occurs during adolescence. The discovery, which the director of NIMH called "a crucial turning point in the fight against mental illness", received a national research award.