Daniel Hart, PhD

Assistant Professor
Department of Biochemistry and Biophysics
Cardiovascular Research Institute
+1 415 514-1281

We are focused on understanding the mechanisms that regulate how and when genes are switched on and off in precise spatiotemporal fashion during cardiovascular development, the gene regulatory networks these genes control, and their impact on the development of the heart, the blood, and blood vessels. Toward this aim, we take advantage of the zebrafish embryo and adult animal models, as well as mammalian tissue culture systems. We are developing optogentic tools for lineage-specific ablation, next generation sequencing, and TALEN and CRISPR nuclease technologies. 

Cardiovascular Gene Regulatory Networks

Our previous studies of the general transcription factor TATA binding protein Related Factor 3 (Trf3) implicated its direct transcriptional target, Mesoderm Posterior a (Mespa), in initiating hematopoiesis in the ventral mesoderm during gastrulation. This conserved bHLH transcription factor is also well known as a master transcriptional regulator of heart development. Indeed, we observed significant heart defects in embryos depleted of Mespa, consistent with observations in multiple species. However the mechanisms by which Mespa regulates the development of the heart muscle and blood, and the relevant target genes controlled by Mespa  (and Mesp1) in vivohave been poorly studied. We are interested in defining gene regulatory networks downstream of this important factor.

Epigenetic Regulation of vertebrate development

During early embryogenesis the developing embryos is sustained by maternally deposited factors during which there is little detectable transcriptional activity. After this period, transcription of the zygotic genome is rapidly activated by mechanisms yet to be fully described. It has been shown that the epigenome is highly dynamic during this time, and it is suggested that this change is directly linked to transcriptional activation. We have developed a method to rapidly profile the epigenetic status of the embryo during early development, and using genetic mutant lines we will test hypotheses about the relevance of specific general transcription factors for this important developmental phenomenon.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Vascular & Cardiac Biology
Research Summary: 
Transcriptional regulation of cardiovascular development and differentiation

Websites

Publications: 

Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex.

Developmental cell

Raices M, Bukata L, Sakuma S, Borlido J, Hernandez LS, Hart DO, D'Angelo MA

Assay for Transposase-Accessible Chromatin with High-Throughput Sequencing (ATAC-Seq) Protocol for Zebrafish Embryos.

Methods in molecular biology (Clifton, N.J.)

Doganli C, Sandoval M, Thomas S, Hart D

a8ß1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism.

eLife

Khalifeh-Soltani A, Ha A, Podolsky MJ, McCarthy DA, McKleroy W, Azary S, Sakuma S, Tharp KM, Wu N, Yokosaki Y, Hart D, Stahl A, Atabai K

An internal promoter underlies the difference in disease severity between N- and C-terminal truncation mutations of Titin in zebrafish.

eLife

Zou J, Tran D, Baalbaki M, Tang LF, Poon A, Pelonero A, Titus EW, Yuan C, Shi C, Patchava S, Halper E, Garg J, Movsesyan I, Yin C, Wu R, Wilsbacher LD, Liu J, Hager RL, Coughlin SR, Jinek M, Pullinger CR, Kane JP, Hart DO, Kwok PY, Deo RC