# SINGLE-CELL ANALYSIS OF SOMATIC MUTATION IN AGING AND NEUROEGENERATIVE DISEASE IN THE HUMAN BRAIN

> **NIH NIH R00** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $247,932

## Abstract

Project Summary/Abstract
Candidate. I have a profound interest in understanding the genetic and epigenetic mechanisms that control
cell state, and have built upon that interest during my research career. As an undergraduate researcher in the
laboratory of Dr. Joanne Wiley at Hofstra University, I studied bacterial sporulation and antibiotic production
using genetics and scanning electron microscopy, resulting in authorship on a peer-reviewed manuscript. As a
Ph.D. candidate in the laboratory of Dr. Rudolf Jaenisch at the Massachusetts Institute of Technology, I worked
on several of projects which resulted in authorship of peer-reviewed manuscripts, related to epigenetics, factor-
mediated reprogramming, and transdifferentiation. In my main thesis work, I used genomics, genetics,
molecular biology, and tissue culture techniques to study cell fate transitions in the development of the
mammalian nervous system, resulting in a first-author publication (Lodato et al., PLoS Genetics, 2013, PMID
23437007). In the first part of my postdoctoral fellowship, in the lab of Dr. Christopher Walsh of Boston
Children’s Hospital and Harvard Medical School, I built upon all these previous experiences, in particular in
using genomics to understand principles of neurobiology, to study somatic mutations in the normal human
brain using cutting-edge single-cell whole genome sequencing (WGS) technologies, resulting in a first-author
manuscript (Lodato et al., Science, 2015, PMID 26430121). This paper was the first published work to
compare the whole-genome rates and characteristics of somatic mutations across normal human individuals,
and the expertise I gained developing that technology has prepared me thoroughly to now compare the rates
and characteristics of somatic mutations between age groups and in human age-related diseases.
 The K99/R00 Pathway to Independence Award is the perfect mechanism to help propel me to my
scientific and career goals. Under this award, I will 1) Execute a research plan to uncover the role of somatic
mutation in aging and in age-related diseases 2) Gain scientific skills and refine my understanding of key
concepts in the fields of aging and bioinformatics 3) Undertake career development activities under the
supervision of my mentor, co-mentor, and other faculty advisors committed to my successful transition from
postdoctoral fellow to independent investigator.
Environment. The proposed Research and Training plans will take place in the laboratory of Christopher A.
Walsh, M.D., Ph.D., within Boston Children’s Hospital (BCH) and Harvard Medical School (HMS). These
institutions comprise a strong, well-established research community, and are committed to the success of the
aims and goals proposed in this application. Dr. Walsh has a strong track record of training postdoctoral
fellows, many of his former trainees now holding tenured or tenure-track faculty positions at academic
institutions. This success stems from the rigorous and supportive...

## Key facts

- **NIH application ID:** 10006779
- **Project number:** 5R00AG054748-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Michael Anthony Lodato
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,932
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006779

## Citation

> US National Institutes of Health, RePORTER application 10006779, SINGLE-CELL ANALYSIS OF SOMATIC MUTATION IN AGING AND NEUROEGENERATIVE DISEASE IN THE HUMAN BRAIN (5R00AG054748-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10006779. Licensed CC0.

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