Research in Dr. Ann Griffith's laboratory focuses on the lymphopoietic stromal microenvironment in the thymus. T lymphocytes are critical mediators of immunity generated in the thymus through mutually inductive “cross-talk” with thymic stromal cells.Age-induced alterations in stromal cells cause substantial thymic atrophy and dysfunction, resulting in diminished T cell production and concomitant immunodeficiencies, including decreased responsiveness to infection and vaccination.
Preserving thymus function therefore holds significant potential to extend the healthspan.However, mechanisms driving age-induced stromal dysfunction have been difficult to resolve because thymic stromal cells are rare and difficult to isolate.
Her lab applies a novel computational deconvolution approach to spatially map stromal gene expression using microdissected whole tissue, eliminating the need for stromal cell isolation.
Some of her lab's goals are to uncover novel lymphopoietic stromal functions in the young, steady state thymus, and to preserve thymus function during aging.
Griffith AV, Venables T, Shi J, Farr A, Van Remmen H, Szweda L, Fallahi M, Rabinovitch P, Petrie H. 2015 Metabolic damage and premature thymus aging caused by stromal catalase deficiency. Cell Reports [In Press].
Bryson JL, Griffith AV, Hughes B, Saito F, Takahama Y, Richie ER, Manley NR. 2013 Cell-Autonomous Defects in Thymic Epithelial Cells Disrupt Endothelial - Perivascular Cell Interactions in the Mouse Thymus.PLoS ONE 8(6), e65196.
Griffith AV, Fallahi M, Venables T, Petrie HT. 2012 Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth. Aging Cell Feb; 11 (1): 169-77.
Griffith AV, Fallahi M, Nakase H, Gosink M, Young B, Petrie HT.2009 Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation. Immunity Dec 18; 31(6):999-1009.
Griffith AV, Cardenas K, Carter C, Gordon J, Iberg A, Engleka K, Epstein JA, Manley NR, Richie ER. 2009 Increased thymus- and decreased parathyroid-fated organ domains in Splotch mutant embryos. Dev Biol. Mar 1;327(1):216-27.
Benavides F*, Venables A*, Poetschke Klug H, Glasscock E, Rudensky A, Gomez M, Palenzuela N, Guenet J, Richie E, Conti C.2001 The CD4 T cell-deficient mouse mutation nackt (nkt) involves a deletion in the cathepsin L (Ctsl) gene. Immunogenetics. Apr;53(3):233-242.*These authors contributed equally to this work.