Investigator:
Michael Lodato, PhD
Name of Institution:
University of Massachusetts Chan Medical School, Worcester, MA
Project Title:
Single-cell whole genome sequencing analysis of DNA damage and somatic mutation in the human Parkinson’s disease brain
Investigator Bio:
Dr. Lodato is an Assistant Professor in the Department of Molecular, Cell, and Cancer Biology at the University of Massachusetts Chan Medical School. The Lodato lab studies the rates, causes, and consequences of somatic mutations in the human brain during aging and disease. Dr. Lodato received his PhD from the Massachusetts Institute of Technology in Cambridge, MA, where he worked on the transcriptional regulation of stem cells in the laboratory of Dr. Rudolf Jaenisch. Dr. Lodato began his studies of somatic mutations in the human brain in 2013 during his postdoctoral fellowship in the laboratory of Dr. Christopher A. Walsh at Boston Children’s Hospital and Harvard Medical School in Boston, MA.
Objective:
To understand the role of somatic mutations in the development of Parkinson’s disease (PD)
Background:
DNA damage is associated with aging and human disease. Damage to DNA can cause permanent changes in the genetic code in cells throughout the brain and body, called somatic mutations. This project aims to ask two specific questions. First, are somatic mutations increased in human PD neurons? Our preliminary data suggests that PD neurons do indeed contain more somatic mutations than age-matched control donor neurons. Second, are there specific somatic mutations that tend to appear in PD neurons, and do they suggest therapeutic targets?
Methods/Design:
We will use new single-cell, whole-genome sequencing of fresh-frozen PD brain samples in this project to identify somatic mutations.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The analysis of somatic mutations in other disease states, such as cancer, has identified new and unexpected treatments. We believe that the mutation signature analysis we propose here may similarly identify therapeutic interventions for PD.