Michael Lodato

Michael Lodato is an Assistant Professor in the Department of Molecular, Cell, and Cancer Biology at the University of Massachusetts Medical School. Mike’s lab focuses on how neuronal somatic mutations generate genetic mosaicism in the human brain. As a Massachusetts Institute of Technology graduate student in the laboratory of Rudolf Jaenisch, he studied transcriptional regulation in embryonic stem cells and neural progenitor cells. Mike then began a postdoctoral fellowship in Christopher A. Walsh’s lab at Boston Children’s Hospital, Harvard Medical School, and the Howard Hughes Medical Institute. As a postdoctoral fellow, he and his collaborators performed the first-ever analysis of somatic single-nucleotide variants (SNVs) in single human neurons. They showed that developmental somatic mutations could be used as a natural lineage barcodes of neural development, allowing single-cell lineage tracing in the human brain for the first time. Next, Mike and his colleagues innovated novel bioinformatic tools to more precisely measure somatic mutation rates in single-cell, whole-genome (scWGS) data. These new tools allowed them to show that somatic mutations increase in human neurons during life, in support of until then unproven hypotheses regarding the mechanism of aging that date back to the 1950s. Mutation accumulation rates and signatures varied across brain regions, and in diseased brains as compared to controls, suggesting specific damage and repair pathways that regulate somatic mutation in the human brain. Currently, Mike is interested in how somatic mutation might play a role in the cell death associated with late-onset neurodegenerative diseases.