Ph.D. (1989) Massachusetts Institute of Technology
Dr. Manley is a member of the UGA Developmental Biology Alliance
My lab is primarily focused on studying the "life history" of the thymus, the primary lymphoid organ responsible for the generation of T cells. This approach encompasses the evolution, fetal development, postnatal function, and aging of this critical organ. Our basic hypothesis is that these diverse aspects of the biology of the organ are controlled by common regulatory networks, cellular dynamics, and physiological processes. We also study the parathyroid, which is required for calcium homeostasis, and has a shared developmental ontogeny with the thymus. We use a variety of approaches to accomplish these goals, including genetic analysis of tissue-specific and inducible mutant mouse strains, comparative and experimental embryology, and immunological techniques.
Evolution of the pharyngeal organs: The thymus and parathyroids are only present in jawed vertebrates. We are using our knowledge of early organogenesis to investigate the evolutionary origins of these organs. This approach may allow us to identify mechanisms by which vertebrates have evolved "newer" functions, such as adaptive immunity, from evolutionarily ancient embryonic structures.
Organogenesis and morphogenesis: Projects include the molecular and cellular control of thymus and parathyroid organogenesis, and crosstalk between thymic epithelial cells and the multiple cell types in the fetal and postnatal thymus.
Thymic epithelial cell development and function: Projects are focused primarily on the role of the Foxn1 transcription factor in thymic epithelial cell differentiation and function, during both fetal development and in the postnatal thymus.
Thymic involution and immunosenescence: The thymus is the earliest organ to degenerate, losing much of its structural and functional integrity by early adulthood. This process of involution is a major contributor to immunosenescence. Our work to date suggests that the molecular mechanisms regulating fetal development may provide insight into the mechanisms regulating thymic involution.
- Bryson, J.L., A.V. Griffith, B. Hughes III, F. Saito, Y. Takahama, E.R. Richie and N.R. Manley. Cell-autonomous defects in thymic epithelial cells disrupt endothelial - perivascular cell crosstalk. PLoS One, in press.
- Garfin, P.M., M. Dullei, J.L. Bryson, T. Serwold, E. Badreddin, C.C. Blackburng, E.R. Richie, K. Weinberg, N.R. Manley, J. Sage and P. Viatour. 2013. Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression. J. Exp. Med., in press.
- Gardiner, J.R., A.L. Jackson, J. Gordon, H. Lickert, N.R. Manley and M.A. Basson. 2012. Localized inhibition of FGF signalling in the third pharyngeal pouch is required for normal thymus and parathyroid organogenesis. Development 139(18): 3456-66.
- Wei, Q., N.R. Manley and B.G. Condie. 2011. Whole mount in situ hybridization of E8.5 to E11.5 mouse embryos. J. Vis Exp. 56: 2797.
- Bryson, J.L., M. Coles and N.R. Manley. 2011. A method for labeling vasculature in embryonic mice. J Vis Exp. 56: e327.
- Liu, Z., L. Chen and N.R. Manley. 2010. Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions. PLoS Genetics 6(12): e1001251.
- Xiao, S. and N.R. Manley. 2010. Impaired thymic selection and abnormal antigen-specific T cell responses in Foxn1Δ/Δ mutant mice. PLoS One 4;5(11): e15396.
- Foster, K., J. Gordon, K. Cardenas, H. Veiga-Fernandes, T. Makinen, V. Pachnis, D. Wilkinson, E. Richie, C.C. Blackburn, N.R. Manley, R. Adams, D. Kioussis and M. Coles. 2010. EphB-Ephrin B2 interactions in the collective migration of thymic primordium during organogenesis. PNAS 107: 13414-9.
- Chen, L., P. Zhao, L. Wells, C.T. Amemiya, B.G. Condie and N.R. Manley. 2010. Mouse and zebrafish Hoxa3 orthologs have non-equivalent in vivo protein function. PNAS 107: 10555-60.
- Gordon, J., S.R. Patel, Y. Mishina and N.R. Manley. 2010. Evidence for an early role for Bmp4 signaling in thymus and parathyroid morphogenesis. Developmental Biology 339: 141-54.
- Fraser, G.J., C.D. Hulsey, R.F. Bloomquist, K. Uyesugi, N.R. Manley and J.T. Streelman. 2009. An ancient gene network is co-opted for teeth on old and new jaws. PLoS Biology 7: e31.
- Griffith, A.V., C. Carter, J. Gordon, A. Iberg, N.R. Manley and E.R. Richie. 2009. Increased thymus- and decreased parathyroid-fated organ domains in Splotch mutant embryos. Developmental Biology 327: 216-27.
- Youm, Y.-H., H. Yang, Y. Sun, R.G. Smith, N.R. Manley, B. Vandanmagsar and V.D. Dixit. 2009. Deficient ghrelin receptor mediated signaling compromises thymic stromal cell microenvironment by accelerating thymic adiposity. J. Biol. Chem. 284: 7068-7077.
- Chen, L., S. Xiao and N.R. Manley. 2009. Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner. Blood 113: 567-74.
- Xiao, S., D.M. Su and N.R. Manley. 2008. T cell development from kit-negative progenitors in the Foxn1D/D mutant thymus. J. Immunology 180: 914-921.