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 email@example.com
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: firstname.lastname@example.org
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.
Loss of Hdac1/2 expression leads to defective lung development.
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.
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.
Wnt5a and Wnt11 are essential for second heart field progenitor development.
Fate Mapping Wnt2+ Cells
Wnt2+ Fate Mapping
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.
- Zheng Cui, MD
- Michael Herriges
- Rachel Kadzik
- Shanru Li, PhD
- Ying Liu, PhD
- Michael Morley, MS
- Tien Peng, MD
- Melinda Snitow
- Kathleen Stewart, PhD
- Daniel Swarr, MD
- Xiaoru Wang
- Yi Wang
- Wang Y, Tian Y, Morley MP, Lu MM, Demayo FJ, Olson EN, Morrisey EE. Dev Cell. Development and regeneration of Sox2+ endoderm progenitors are regulated by a Hdac1/2-Bmp4/Rb1 regulatory pathway. Dev. Cell. 2013 Feb 25;24(4):345-58. doi: 10.1016/j.devcel.2013.01.012.
- Miller MF, Cohen ED, Baggs JE, Hogenesch JB, Morrisey EE. High throughput genomic screen identifies multiple factors that promote cooperative Wnt signaling. PLoS One. 2013;8(1):e55782. doi: 10.1371/journal.pone.0055782. Epub 2013 Jan 31.
- Miller MF, Cohen ED, Baggs JE, Lu MM, Hogenesch JB, Morrisey EE.Wnt ligands signal in a cooperative manner to promote foregut organogenesis. Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15348-53. Epub 2012 Sep 4.
- Li S, Wang Y, Zhang Y, Lu MM, DeMayo FJ, Dekker JD, Tucker PW, Morrisey EE. Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2. Development. 2012 Jul;139(14):2500-9. doi: 10.1242/dev.079699. Epub 2012 Jun 6.
- Cohen ED, Miller MF, Wang Z, Moon RT, Morrisey EE. Wnt5a and Wnt11 are essential for second heart field progenitor development. Development. 2012 Jun;139(11):1931-40. doi: 10.1242/dev.069377.
- Goss AM, Tian Y, Cheng L, Yang J, Zhou D, Cohen ED, Morrisey EE. Wnt2 signaling is necessary and sufficient to activate the airway smooth muscle program in the lung by regulating myocardin/Mrtf-B and Fgf10 expression. Dev Biol. 2011 Aug 15;356(2):541-52. doi: 10.1016/j.ydbio.2011.06.011. Epub 2011 Jun 16.
- Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell. 2011 Apr 8;8(4):376-88. doi: 10.1016/j.stem.2011.03.001. Erratum in: Cell Stem Cell. 2012 Dec 7;11(6):853.
- Tian Y, Zhang Y, Hurd L, Hannenhalli S, Liu F, Lu MM, Morrisey EE. Regulation of lung endoderm progenitor cell behavior by miR302/367. Development. 2011 Apr;138(7):1235-45. doi: 10.1242/dev.061762. Epub 2011 Feb 24.
- Tian Y, Yuan L, Goss AM, Wang T, Yang J, Lepore JJ, Zhou D, Schwartz RJ, Patel V, Cohen ED, Morrisey EE. Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development. Dev Cell. 2010 Feb 16;18(2):275-87. doi: 10.1016/j.devcel.2010.01.008.
- Goss AM, Tian Y, Tsukiyama T, Cohen ED, Zhou D, Lu MM, Yamaguchi TP, Morrisey EE. Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut. Dev Cell. 2009 Aug;17(2):290-8. doi: 10.1016/j.devcel.2009.06.005.