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: 

Targeting transcription in heart failure via CDK7/12/13 inhibition.

Nature communications

Hsu A, Duan Q, Day DS, Luo X, McMahon S, Huang Y, Feldman ZB, Jiang Z, Zhang T, Liang Y, Alexanian M, Padmanabhan A, Brown JD, Lin CY, Gray NS, Young RA, Bruneau BG, Haldar SM

Transcription factor protein interactomes reveal genetic determinants in heart disease.

Cell

Gonzalez-Teran B, Pittman M, Felix F, Thomas R, Richmond-Buccola D, Hüttenhain R, Choudhary K, Moroni E, Costa MW, Huang Y, Padmanabhan A, Alexanian M, Lee CY, Maven BEJ, Samse-Knapp K, Morton SU, McGregor M, Gifford CA, Seidman JG, Seidman CE, Gelb BD, Colombo G, Conklin BR, Black BL, Bruneau BG, Krogan NJ, Pollard KS, Srivastava D

Brahma safeguards canalization of cardiac mesoderm differentiation.

Nature

Hota SK, Rao KS, Blair AP, Khalilimeybodi A, Hu KM, Thomas R, So K, Kameswaran V, Xu J, Polacco BJ, Desai RV, Chatterjee N, Hsu A, Muncie JM, Blotnick AM, Winchester SAB, Weinberger LS, Hüttenhain R, Kathiriya IS, Krogan NJ, Saucerman JJ, Bruneau BG

Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids.

Cell stem cell

Silva AC, Matthys OB, Joy DA, Kauss MA, Natarajan V, Lai MH, Turaga D, Blair AP, Alexanian M, Bruneau BG, McDevitt TC