- 81 Research Drive, Scarborough, Maine 04074
BS: Biology, Stony Brook University
PhD: Massachusetts Institute of Technology (MIT)
Postdoctoral Training: Whitehead Institute, MIT
Our laboratory studies genes important for embryonic development in mice, and the relation between mutations in these genes and both congenital and acquired human disease. Our analyses focus on the Notch pathway, an evolutionarily conserved cell communication and signaling system, and on genes of the Snail superfamily, which encode transcriptional repressor proteins.
We have created and analyzed numerous genetically engineered mouse models to understand the essential functions of individual components of these pathways. We have also generated mouse models for inherited human disease syndromes such as Alagille syndrome, and for common birth defects such as cleft palate, craniosynostosis, and congenital heart defects, such as outflow tract patterning defects and patent ductus arteriosus. Current areas of interest include the role of Notch signaling in cardiovascular development, and in skeletal muscle and mesenchymal stem cells.
Figure 1. Defects in embryonic development in Notch pathway mutant mice. In all panels, the control embryo is on the left, with the mutant on the right. A) Patent ductus arteriosus in Jag1 conditional mutant embryos. B) Rib and vertebral defects in Notch-regulated ankyrin repeat (Nrarp) mutant embryos. C) Defects in formation of sensory cells of the inner ear in Jag1 conditional mutant embryos. D) Kidney defects in Notch2 hypomorphic mutant embryos.
Scientific Manager I
Research Interests: Mouse embryonic development
Blackwood, C.A., A. Bailetti, S. Nandi, T. Gridley and J.M. Hébert. (2020) Notch Dosage: Jagged1 haploinsufficiency is associated with reduced neuronal division and disruption of periglomerular interneurons in mice. Front Cell Dev Biol. 8:113.
Peterson SM, Turner JE, Harrington A, Davis-Knowlton J, Lindner V, Gridley T, Vary CPH, Liaw L (2018) Notch2 and proteomic signatures in mouse neointimal lesion formation. Arterioscler Thromb Vasc Biol. 38:1576-1593.
Krebs, L.T., C.R. Norton and T. Gridley. (2016) Notch signal reception is required in vascular smooth muscle cells for ductus arteriosus closure. Genesis 54:86-90.
Basch, M.L., R. Brown, H.-I. Jen, F. Semerci, F. Depreux, R. Edlund, H. Zhang, C.R. Norton, T. Gridley, S. Cole, A. Doetzlhofer, M. Maletic-Savatic, N. Segil and A.K. Groves. (2016) Fringe proteins fine-tune Notch signaling to set the boundary of the organ of Corti and establish sensory cell fates. Elife:5.
Young, K., L.T. Krebs, E. Tweedie, B. Conley, M. Mancini, H. Arthur, L. Liaw, T. Gridley and C.P. Vary. (2016). Endoglin is required in Pax3-derived cells for embryonic blood vessel formation. Dev Biol. 409:95-105.
Gridley, T. (2016) Twenty years in Maine: integrating insights from developmental biology into translational medicine in a small state. Curr Top Dev Biol. 116:435-443.
Pardo-Saganta, A., P.R. Tata, B.M. Law, B. Saez, R.D. Chow, M. Prabhu, T. Gridley and J. Rajagopal. (2015) Parent stem cells can serve as niches for their daughter cells. Nature 523:597-601.
Rostama, B., J.E. Turner, G.T. Seavey, C.R. Norton, T. Gridley, C.P. Vary and L. Liaw. (2015) DLL4/Notch1 and BMP9 interdependent signaling induces human endothelial cell quiescence via P27KIP1 and Thrombospondin-1. Arterioscler Thromb Vasc Biol. 35:2626-2637.
Horvay, K., T. Jarde, F. Casagranda, V.M. Perreau, K. Haigh, C.M. Nefzger, R. Akhtar, T. Gridley, G. Berx, J.J. Haigh, N. Barker, J.M. Polo, G.R. Hime and H.E. Abud. (2015) Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium. EMBO J. 34:1319-1335.
Villarejo, A., P. Molina-Ortiz, Y. Montenegro, G. Moreno-Bueno, S. Morales,V. Santos, T. Gridley, M.A. Pérez-Moreno, H. Peinado, F. Portillo, C. Calés and A. Cano. (2015) Loss of Snail2 favors skin tumor progression by promoting the recruitment of myeloid progenitors. Carcinogenesis 36:585-597.
Castillo-Lluva, S., L. Hontecillas-Prieto, A. Blanco-Gómez, M. del Mar Sáez-Freire, B. García-Cenador, J. García-Criado, M. Pérez-Andrés, A. Orfao de Matos, M. Cañamero, T. Gridley, J.-H. Mao, A. Castellanos-Martín and J. Pérez-Losada. (2015) A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development. Oncogene 34:4777–4790.
Gridley, T., and A.K. Groves. (2014) Overview of genetic tools and techniques to study Notch signaling in mice. Meth Molec Biol. 1187:47-61.
Gridley, T., and S. Kajimura. (2014) Lightening up a notch: Notch regulation of energy metabolism. Nature Med. 20:811-812.
Zander, M., G.I. Cancino, T. Gridley, D.R. Kaplan and F.D. Miller (2014) The Snail transcription factor regulates the numbers of neural precursor cells and newborn neurons throughout mammalian life. PLoS One 9:e104767
Battle, R., L. Alba-Castellón, J. Loubat-Casanovas, E. Armenteros, C. Franci, J. Stanisavljevic, R. Banderas, J. Martin-Caballero, F. Bonilla, J. Baulida, J.I. Casal, T. Gridley, and A. García de Herreros. (2013) Snail1 controls TGF-β responsiveness and differentiation of Mesenchymal Stem Cells. Oncogene 32:3381-3389.
Xu, J., and T. Gridley. (2013) Notch2 is required in somatic cells for ovarian germ cell nest breakdown and primordial follicle formation. BMC Biol. 11:13.
Chen, Y., and T. Gridley. (2013) Compensatory regulation of the Snai1 and Snai2 genes during chondrogenesis. J Bone Min Res. 28:1412-1421.
Chen, Y., and T. Gridley. (2013) The SNAI1 and SNAI2 proteins occupy their own and each other’s promoter during chondrogenesis. Biochem Biophys Res Commun. 435:356-360.
Bradley, C.K., C.R. Norton, Y. Chen, X. Han, C.J. Booth, J.K. Yoon, L.T. Krebs and T. Gridley. (2013) The Snail family gene Snai3 is not essential for embryogenesis in mice. PLoS One 8:e65344.
Norton, C.R., Y. Chen, X. Han, C.K. Bradley, L.T. Krebs, J.K. Yoon and T. Gridley. (2013) Absence of a major role for the Snai1 and Snai3 genes in regulating skeletal muscle regeneration in mice. PLoS Curr Musc Dystrophy. doi: 10.1371/ currents.md.e495b27ee347fd3870a8316d4786fc17.
- Professor, Department of Medicine, Tufts University School of Medicine, Boston, MA
- Professor, Tufts Clinical and Translational Science Institute, Tufts University School of Medicine, Boston, MA
- Faculty Member, Molecular, Cell, and Developmental Biology Graduate Program, Tufts University Graduate School of Biomedical Sciences, Boston, MA
- Member, Graduate Faculty, Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME
- Adjunct Faculty, The Jackson Laboratory, Bar Harbor, ME
- Editorial Board, Genesis
- External Advisory Board, Jackson Laboratory Gene Expression Database
- Reviewer, Genetics of Health and Disease Study Section, National Institutes of Health (2012)
- Reviewer, Development 2 Study Section, National Institutes of Health (2012, 2013)
- Member, American Heart Association
- Vice Chair, Maine Medical Center Institutional Review Board
- Lecturer, Cell Biology of Tissue Development and Function, Graduate School of Biomedical Sciences, University of Maine, Orono
- Lecturer (2015), Advanced Mouse Modeling: Relevance to Human Disease, Graduate School of Biomedical Sciences, University of Maine, Orono