Penn Cardiovascular Institute

Morrisey Lab

Contact the Lab

Muredach P. Reilly, MBBCH, MSCE

Edward E. Morrisey, PhD
Principal Investigator

Edward E. Morrisey, PhD
11-124 Smilow Center for Translational Research
3400 Civic Center Boulevard, Bldg. 421
Philadelphia, PA 19104-5159
Office: 215-573-3010
Fax: 215-573-2094
emorrise@mail.med.upenn.edu
http://www.med.upenn.edu/morriseylab/index.shtml

Kathleen Stewart, PhD
Research Scientist/Lab Manager
11-101A Smilow Center for Translational Research
3400 Civic Center Boulevard, Bldg. 421
Philadelphia, PA 19104-5159
Office: 215-573-8404
Fax: 215-579-7884
stewart7@mail.med.upenn.edu

 

Overview

The Morrisey lab studies the developmental pathways and factors that are critical for building the cardiopulmonary system. Using a combination of mouse genetics, biochemistry, and genomic analysis, we seek to better understand how the lung and heart develop, how developmental pathways are disrupted in human cardiopulmonary disease, and whether such pathways and factors can be harnessed to promote pulmonary and cardiac regeneration in the adult.

Reagents and Protocols

For access to mouse lines or to request reagents please contact Dr. Morrisey directly at emorrise@mail.med.upenn.edu

Open Positions Available

We currently have open Post Doctoral positions available for talented and creative individuals. Please email inquiries with a cover letter, CV and three references to Dr. Edward Morrisey at: emorrise@mail.med.upenn.edu

Research Projects

Lung Development

Our interests have focused on the role of critical developmental signaling pathways such as Wnt signaling as well as important transcription factors including Foxp1/2/4 and Gata6. Our data has shown that Wnt signaling is uniquely required for lung endoderm specification. Loss of the critical Wnt ligands Wnt2/2b leads to complete respiratory agenesis as noted by lack of Nkx2.1 expression.

Our lab originally cloned the Foxp1/2/4 subfamily of forkhead transcription factors in 2001. We have shown that these factors play key roles in regulating both lung and cardiac development. Recently, we have shown that Foxp1/4 are essential for restricting secretory lineage differentiation and combined loss of these factors leads to a default differentiation into the goblet cell lineage. We continue to explore the role of these factors in lung development by using a combination of conditional mouse mutants along with genomic analysis to determine how Foxp1/2/4 define the lung endoderm progenitor lineage within the foregut.

Recently we have become interested in the role of chromatin remodeling complexes that regulate lung development and regeneration. We demonstrated that Foxp1/2/4, which act as potent transcriptional repressors, interact with the NuRD chromatin remodeling complex. The repressive activity mediated by Foxp1/2/4 requires histone deactylase (HDAC) activity and HDACs are an essential component of NuRD and other chromatin remodeling complexes. The role of HDACs in development, cellular physiology, and disease states is an area of active investigation in our laboratory.

Cardiac Development

Our lab has a strong ongoing interest in the role of Wnt signaling in cardiovascular development. We have shown that early Wnt/beta-catenin signaling is required for second heart field (SHF) progenitor expansion. Using a series of unique mouse genetic models we have also shown that the Wnt2 ligand is required for development of the posterior pole of the heart including the inflow tract and pulmonary veins.

Fate Mapping Wnt2+ Cells

We have recently fate mapped Wnt2+ cells using a novel Wnt2-creERT2 mouse line and have shown that these cells can contribute to different mesenchymal and vascular lineages in the heart and lung in a temporal specific fashion. We will use the Wnt2-creERT2 mouse line along with other novel tools generated in our lab and other labs to define the importance of Wnt signaling in cardiovascular development as well as in the generation of cardiovascular cell lineages from pluripotent stem cells.

Members

  • Zheng Cui, MD
  • Michael Herriges
    PhD Student
  • Rachel Kadzik
    PhD Student
  • Shanru Li, PhD
  • Ying Liu, PhD
  • Michael Morley, MS
  • Tien Peng, MD
  • Melinda Snitow
    PhD Student
  • Kathleen Stewart, PhD
  • Daniel Swarr, MD
  • Xiaoru Wang
    PhD Student
  • Yi Wang
    PhD Student

Selected Publications

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