The Tapscott Lab studies gene transcription in a chromatin context in normal development and disease, with special emphasis on the molecular mechanisms of cell specification and differentiation. Recent work has focused on the transcription factor DUX4 and related proteins and their role in regulating early pluripotent stem cell specification, development, and disease, including cancer and muscular dystrophy. In addition, the lab studies the molecular and genomic regulation of cell specification using myogenesis and neurogenesis as model systems.

Projects

Wellstone Muscular Dystrophy Specialized Research Center (Seattle) (PI: Chamberlain)
Sponsor: NIH/NIAMS
Award Number: 2 P50 AR065139
Award Dates: 07/01/2018 – 08/31/2023

This proposal addresses the remaining barriers to successful clinical trials in common forms of muscular dystrophy. Specifically, it improves the function of potentially curative gene therapy approaches and identifies measurements that will determine whether the clinical trials result in beneficial results. Project 2 will identify the measurements necessary to conduct rigorous and efficient therapeutic trials in facioscapulohumeral dystrophy (FSHD). Specifically, it determine the value of MRI characteristics and candidate molecular biomarkers for predicting disease activity and progression.

Molecular Markers of FSHD (PI: Tapscott)
Sponsor: Friends of FSH Research
Project Dates: 05/01/2023 – 04/30/2026

The goals of this project are first to determine whether a new model of FSHD shows the same molecular progression as we have characterized in human FSHD, and second, to sequence B cell receptor (BCR) and T cell receptor (TCR) sequences in muscle from FSHD to determine whether there is an oligoclonal expansion of a subset of T and B cells that would support an immune role in disease progression.

D4Z4 Coding Transcripts and FSHD (PI: Tapscott)
Sponsor: NIH/NIAMS
Award Number: 5 R01 AR045203
Project Dates: 02/15/2016 – 12/31/2025

The proposed research will identify the molecular mechanisms of cellular toxicity and dysregulation induced by DUX4 through modulation of RNAs, double-stranded RNAs, and the innate immune response pathways induced by double-stranded RNAs.

SMCHD1 Pathways as Candidate Targets for FSHD (PI: Tapscott)
Sponsor: NIH/NIAMS
Award Number: R01 AR066248
Project Dates: 04/25/2014 – 06/30/2025

The proposed research will identify the fundamental molecular mechanisms that epigenetically repress the D4Z4 region through the production, modification, stability and interacting partners of SMCHD1. The health relevance of this research is that the failure of these mechanisms results in facioscapulohumeral muscular dystrophy and the proposed studies will provide the basis for future therapeutic development.