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Benoit Bruneau, PhD
Director and Senior Investigator, Gladstone Institute of Cardiovascular Disease

Other Professional Titles

Professor, University of California, San Francisco, Department of Pediatrics
William H. Younger Chair in Cardiovascular Research

Phone

(415) 734-2708

Fax

(415) 355-0960

Assistant

Elana Lewis
(415) 734-2705

On The Web

Areas of Investigation

Bruneau’s laboratory demonstrated the interactions between three disease-related transcription factors—TBX5, NKX2-5, and GATA4—at a genome scale. They found that these proteins co-localize across the genome to regulate the cardiac gene expression program, and elucidated some of the rules by which they co-recruit one another to active cardiac enhancers. The scientists also identified a protein-protein interaction that facilitates their shared binding, through the crystal structure of TBX5, NKX2-5, and their shared DNA binding site.

In addition, the team studied the roles played by another transcription factor, CTCF, in embryonic stem cells. Using a new system that allows rapid and reversible depletion of CTCF, they showed that the three-dimensional organization of chromatin into structures called “topologically associated domains” is highly dependent on CTCF. Through these studies, they discovered new rules about chromatin organization and how it impacts gene regulation. 

They also examined the importance of a disease-related histone-modifying enzyme called KMT2D. The gene that encodes this protein is often mutated in congenital heart disease. They deleted KMT2D in mice and showed that it controls a set of genes essential for embryonic cardiac function by depositing at regulatory elements in the genome a specific type of histone modification that helps genes become activated.

Lab Focus

What are the roles of chromatin remodeling and modifying complexes in heart development and cardiac lineage determination?
How do chromatin remodeling complexes and epigenetic regulators function to activate specific cardiac genes and what is the importance of this level of regulation for heart development and function?
How do disease-related transcription factors interact with chromatin modifying complexes to regulate cardiac morphogenesis, and how does this interaction go wrong in heart disease?
How are important morphogenetic processes such as cardiac septation regulated at the cellular level?

Achievements

Created mouse models of congenital heart defects commonly found in children, including septal defects (“holes in the heart”) and conduction defects, or arrhythmias, by manipulating cardiac regulatory genes.
Uncovered a revolutionary role for Tbx5 in the evolution of patterning of the heart.
Begun to understand the roles played in heart development by a heart-restricted chromatin remodeling complex subunit, Baf60c, which illustrates the novel concept of tissue-specific remodeling complexes.
Identified a minimal "cocktail" of factors that can induce cardiac differentiation from mouse mesoderm.
Deciphered the epigenetic blueprint of cardiac differentiation.

Affiliations

  • Developmental Biology (Editorial Board)
  • Circulation Research (Editorial Board)
William H. Younger Chair in Cardiovascular Research
  • Circulation: Cardiovascular Genetics (Editorial Board)
  • Developmental Dynamics (Editorial Board)
  • American Heart Association Western Consortium (Grant Review Panel)
  • American Heart Association Western Consortium Study Group 3A (Co-chair)
  • iPierian, Inc. (Scientific Advisory Board)
  • Silver Creek Pharmaceuticals, Inc. (Scientific Advisor)

Professional titles

Professor, University of California, San Francisco, Department of Pediatrics
William H. Younger Chair in Cardiovascular Research

Education

1990
BS
  • University of Ottawa
1996
PhD
  • University of Ottawa

Honors and Awards

2012 American Heart Association (Fellow)
2010 Established Investigator Award (5 years), Lawrence J. and Florence A. DeGeorge Charitable Trust/American Heart Association
2003 Premier’s Research Excellence Award (Ontario)
2001 New Investigator Award, Heart and Stroke Foundation of Canada/Canadian Institutes of Health Research