# Defining the disorders of genome organization

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $197,518

## Abstract

This application proposes a five-year mentored research and training experience that will prepare Dr. Philip
Boone to be a leader in the fields of medical neurogenetics, genomics, and disease modeling. The candidate
has an MD and PhD in Molecular and Human Genetics from Baylor College of Medicine, where he studied
genomic structural variation and Mendelian disease with Dr. James Lupski. He is now completing residency
training in Pediatrics and Clinical Genetics at Boston Children’s Hospital (BCH) while pursuing postdoctoral
training with Dr. Michael Talkowski at Massachusetts General Hospital (MGH) and the Broad Institute. Dr.
Boone’s career goal is to become a physician-scientist and to advance care for patients with genetic disease.
This project will greatly advance those goals and facilitate foundational discoveries for his independent research
program as he seeks to delineate a new class of neurogenetic disease: the disorders of genome organization.
 This emerging class of genomic disorders involve mutations encoding components that regulate the 3D
organization of chromosomes. This work will elucidate the molecular and phenotypic consequences of mutation
of these genes. Specifically, Dr. Boone proposes to: 1) model these disorders using patient-derived and
CRISPR-generated iPSC and neural lineage cell lines; 2) Characterize alterations to the 3D genome (via Hi-C)
and transcriptome (via RNA-seq), as well as the human phenotype (via exams and history); and 3) Attempt to
correct these defects in cellular models via CRISPRa/i of genes in this network. The work will improve the
diagnosis and understanding of these disorders and lay the groundwork for targeted therapy. It will also generate
fundamental knowledge about the spatial organization of the genome and the regulatory purpose it serves.
 The career development plan includes training in in vitro neurodevelopmental disease modeling, design and
analysis of functional genomic experiments, and cohort building. The candidate will learn all the requisite skills
needed for an independent research career, including supervising trainees and staff, responsible conduct of
research, grant writing, scientific communication, and lab management. His primary mentor, Dr. Michael
Talkowski, is Associate Professor of Neurology at MGH and Institute Member at the Broad Institute. Dr.
Talkowski is an experienced mentor and recognized expert in statistical, computational, and functional genomics.
His co-mentor, Dr. Gusella, is a renowned molecular geneticist with considerable experience in disease modeling
and molecular mechanisms. The mentorship committee also includes diverse expertise in genome organization
and neuronal function (Drs. Leonid Mirny and Kristen Brennand), clinical phenotyping (Dr. Angela Lin), and
genetic counseling (Diane Lucente). Dr. Boone thus has access to the unique convergence of leading-edge
genomics training environments at MGH, Harvard, MIT, and the Broad Institute, and remarkable physic...

## Key facts

- **NIH application ID:** 10038676
- **Project number:** 1K08NS117891-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Philip Michael Boone
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,518
- **Award type:** 1
- **Project period:** 2020-08-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038676

## Citation

> US National Institutes of Health, RePORTER application 10038676, Defining the disorders of genome organization (1K08NS117891-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10038676. Licensed CC0.

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