Benoit Bruneau, PhD

Professor
Department of Pediatrics
+1 415 734-2708
Research Description: 

The main focus of our lab is to understand how a heart becomes a heart: what cell lineage decisions take place to direct cardiac differentiation, and what morphogenetic and patterning processes occur to assemble all of the heart's components into a functional organ. We are primarily interested in regulation of these processes by transcriptional regulatory mechanisms that include DNA-binding transcription factors, chromatin remodeling complexes, and histone modifications. We have used this knowledge to understand disease mechanisms, but also to devise strategies for cardiac regeneration.

Why study heart development? We believe that primary defects in patterning in early heart development are at the root of congenital heart defects, which affect approximately 1% of live-born children, and we want to understand how these defects occur, to perhaps be able to uncover new and improved diagnostic or even therapeutic options. Also, by understanding how cardiac lineage specification occurs, we can better design stem cell-based interventions of cardiac repair, based on the knowledge of what drives an uncommitted cell towards a specific cardiac fate. We have recently focused our efforts on cardiac chromatin remodeling and modification factors, enzymes that unwind DNA or modify histones to turn genes on or off. We are particularly interested in how these factors control cardiac cell lineage decisions. These chromatin remodeling factors may also be key to pushing a stem cell into becoming a heart cell, perhaps opening up new avenues for cardiac regenerative medicine.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Vascular & Cardiac Biology
Research Summary: 
Transcriptional regulation of cardiac morphogenesis and differentiation
Publications: 

Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project.

Molecular cell

Dekker J, Alber F, Aufmkolk S, Beliveau BJ, Bruneau BG, Belmont AS, Bintu L, Boettiger A, Calandrelli R, Disteche CM, Gilbert DM, Gregor T, Hansen AS, Huang B, Huangfu D, Kalhor R, Leslie CS, Li W, Li Y, Ma J, Noble WS, Park PJ, Phillips-Cremins JE, Pollard KS, Rafelski SM, Ren B, Ruan Y, Shav-Tal Y, Shen Y, Shendure J, Shu X, Strambio-De-Castillia C, Vertii A, Zhang H, Zhong S

A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors.

Development (Cambridge, England)

Krup AL, Winchester SAB, Ranade SS, Agrawal A, Devine WP, Sinha T, Choudhary K, Dominguez MH, Thomas R, Black BL, Srivastava D, Bruneau BG

Smarcd3 is an epigenetic modulator of the metabolic landscape in pancreatic ductal adenocarcinoma.

Nature communications

Ferguson LP, Gatchalian J, McDermott ML, Nakamura M, Chambers K, Rajbhandari N, Lytle NK, Rosenthal SB, Hamilton M, Albini S, Wartenberg M, Zlobec I, Galván JA, Karamitopoulou E, Vavinskaya V, Wascher A, Lowy AM, Schürch CM, Puri PL, Bruneau BG, Hargreaves DC, Reya T

Transcription Factor GATA4 Regulates Cell Type-Specific Splicing Through Direct Interaction With RNA in Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitors.

Circulation

Zhu L, Choudhary K, Gonzalez-Teran B, Ang YS, Thomas R, Stone NR, Liu L, Zhou P, Zhu C, Ruan H, Huang Y, Jin S, Pelonero A, Koback F, Padmanabhan A, Sadagopan N, Hsu A, Costa MW, Gifford CA, van Bemmel JG, Hüttenhain R, Vedantham V, Conklin BR, Black BL, Bruneau BG, Steinmetz L, Krogan NJ, Pollard KS, Srivastava D