Departments & Divisions
Institutes and Centers
Deparmtent of Microbiology, Immunology & Molecular Genetics
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. Long-term goals of the lab include revealing novel lymphopoietic stromal functions in the young, steady state thymus, and boosting thymus function during aging.
Dr. Griffith’s research interests lie in the identification of lymphopoietic signals provided by the stromal microenvironment in the thymus, the biology of thymic stromal cells, and the mechanisms and consequences (including diminished vaccine response and increased susceptibility to infection) of age-induced thymic atrophy. The impact of age-induced atrophy on T cell production, which is pronounced by young adulthood, is not limited to the elderly, but is also apparent in young adults when lymphopenia is actively induced, such as in patients receiving myeloablative therapy and bone marrow stem cell transplants.
Hester AK, Semwal MK, Cepeda S, Xiao Y, Rueda M, Wimberly K, Venables T, Dileepan T, Kraig E, Griffith AV. Redox regulation of age-associated defects in generation and maintenance of T cell self-tolerance and immunity to foreign antigens. Cell Reports. In Press. 2022 February 15.
Semwal MK, Jones NE, Griffith AV. Metabolic Regulation of Thymic Epithelial Cell Function. Front Immunol. 2021;12:636072. doi: 10.3389/fimmu.2021.636072. eCollection 2021. Review. PubMed PMID: 33746975; PubMed Central PMCID: PMC7968369.
Venables T, Griffith AV, DeAraujo A, Petrie HT. Dynamic changes in epithelial cell morphology control thymic organ size during atrophy and regeneration. Nat Commun. 2019 Sep 27;10(1):4402. doi: 10.1038/s41467-019-11879-2. PubMed PMID: 31562306; PubMed Central PMCID: PMC6765001.
Cepeda, S., Cantu,C., Orozco ,S., Xiao, Y., Brown, Z., Semwal,M.K., Venables, T., Anderson, M.S., Griffith, A.V. 2018 Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens. Cell Reports.http://www.cell.com/cell-reports/fulltext/S2211-1247(18)30032-9
Griffith AV, Venables T, Shi J, Farr A, Van Remmen H, Szweda L, Fallahi M, Rabinovitch P, Petri H. 2015 Metabolic damage and premature thymus aging caused by stromal catalase deficiency. Cell Reports.http://www.cell.com/cell-reports/fulltext/S2211-1247%2815%2900734-2
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.