Benoit Bruneau, PhD

Professor
Department of Pediatrics
+1 415 734-2708

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.

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

The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage.

Genome biology

Shaffer HB, Minx P, Warren DE, Shedlock AM, Thomson RC, Valenzuela N, Abramyan J, Amemiya CT, Badenhorst D, Biggar KK, Borchert GM, Botka CW, Bowden RM, Braun EL, Bronikowski AM, Bruneau BG, Buck LT, Capel B, Castoe TA, Czerwinski M, Delehaunty KD, Edwards SV, Fronick CC, Fujita MK, Fulton L, Graves TA, Green RE, Haerty W, Hariharan R, Hernandez O, Hillier LW, Holloway AK, Janes D, Janzen FJ, Kandoth C, Kong L, de Koning AP, Li Y, Literman R, McGaugh SE, Mork L, O'Laughlin M, Paitz RT, Pollock DD, Ponting CP, Radhakrishnan S, Raney BJ, Richman JM, St John J, Schwartz T, Sethuraman A, Spinks PQ, Storey KB, Thane N, Vinar T, Zimmerman LM, Warren WC, Mardis ER, Wilson RK

Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network.

Proceedings of the National Academy of Sciences of the United States of America

Zhang SS, Kim KH, Rosen A, Smyth JW, Sakuma R, Delgado-Olguín P, Davis M, Chi NC, Puviindran V, Gaborit N, Sukonnik T, Wylie JN, Brand-Arzamendi K, Farman GP, Kim J, Rose RA, Marsden PA, Zhu Y, Zhou YQ, Miquerol L, Henkelman RM, Stainier DY, Shaw RM, Hui CC, Bruneau BG, Backx PH

A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia.

Development (Cambridge, England)

Flenniken AM, Osborne LR, Anderson N, Ciliberti N, Fleming C, Gittens JE, Gong XQ, Kelsey LB, Lounsbury C, Moreno L, Nieman BJ, Peterson K, Qu D, Roscoe W, Shao Q, Tong D, Veitch GI, Voronina I, Vukobradovic I, Wood GA, Zhu Y, Zirngibl RA, Aubin JE, Bai D, Bruneau BG, Grynpas M, Henderson JE, Henkelman RM, McKerlie C, Sled JG, Stanford WL, Laird DW, Kidder GM, Adamson SL, Rossant J

The functional landscape of mouse gene expression.

Journal of biology

Zhang W, Morris QD, Chang R, Shai O, Bakowski MA, Mitsakakis N, Mohammad N, Robinson MD, Zirngibl R, Somogyi E, Laurin N, Eftekharpour E, Sat E, Grigull J, Pan Q, Peng WT, Krogan N, Greenblatt J, Fehlings M, van der Kooy D, Aubin J, Bruneau BG, Rossant J, Blencowe BJ, Frey BJ, Hughes TR