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Steve McCarroll is an institute member of the Ó³»­´«Ã½ of MIT and Harvard, and director of genomic neurobiology for the Ó³»­´«Ã½â€™s Stanley Center for Psychiatric Research. He is also Dorothy and Milton Flier Professor of Biomedical Science and Genetics in Harvard Medical School’s Department of Genetics and Blavatnik Institute, and a Howard Hughes Medical Institute (HHMI) investigator.

McCarroll and the scientists in his lab use genetics, molecular biology, and invent new laboratory and computational approaches, to reveal the ways in which genomes vary from person to person and the precise ways that genetic variation leads to human disease. By inventing and applying new approaches to study the brain, his research team is uncovering the key molecular and cellular events in the development of Huntington's disease, schizophrenia, and other brain illnesses. The aspiration is that such discoveries will lead to new, innovative therapies.

McCarroll’s human genome research revealed that human genomes commonly vary at large scales, exhibiting deletion, duplication, inversion, and other rearrangements of long genomic segments. His lab members developed widely used approaches for identifying and characterizing such variation in people’s genomes, and used them to discover the contribution of the complement component (C4) genes to schizophrenia. They also discovered the phenomenon of clonal hematopoiesis, a common pre-cancerous condition of the human blood.

McCarroll’s lab also developed a technology (called droplet-based single-cell RNA-seq, or Drop-Seq) that made it possible to analyze gene expression in tens of thousands of individual cells at once. The technology is widely used in biology today and has enabled the creation of human cell atlases. Scientists in the lab are using the approach to understand brain function and brain disorders in terms of the behavior of specific kinds of cells.

By combining human genetics with these new biological tools, McCarroll’s lab is working to discover how genetic risk factors give rise to key molecular and cellular events in the development of schizophrenia and bipolar disorder. Their work combines genome-wide data, collected from tens of thousands of patients, with focused molecular biological experiments in neurons and brains. McCarroll and his group seek to understand how human biology changes under the influence of these genetic variants – what genes and proteins are affected and in what populations of cells, and how the molecular biology of these cells is affected as a consequence.

Recently, his team made a discovery that fundamentally reshaped the scientific understanding of Huntington’s disease. The team discovered a surprising mechanism by which the inherited genetic mutation (a DNA repeat) known to cause the fatal neurodegenerative disorder leads to the death of brain cells. They demonstrated that this DNA repeat is actually innocuous in the form in which it is inherited from parents, but slowly expands in certain brain cells throughout a person's life – and becomes toxic only when it has become extremely long. This insight is already having an enormous impact, opening the door to entirely new therapeutic strategies – including potential ways to delay or even prevent the disease – that are now the focus of efforts in many pharmaceutical and biotechnology companies. The possibility that similar dynamics underlie many other DNA-repeat disorders is a current focus of work in the lab.

McCarroll’s research draws upon his training in molecular neuroscience and human genetics. He earned his Ph.D. in neuroscience at the University of California, San Francisco in the lab of Cori Bargmann. He completed his postdoctoral fellowship in the lab of David Altshuler (formerly of the Ó³»­´«Ã½, Harvard, and MIT) studying human genome variation and the genetic basis of common disease.