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DepartmentMicrobiology, Immunology & Molecular Genetics
Griffith, Ann V., Ph.D.
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.
Ph.D., University of Texas Health Science Center at Houston-M.D. Anderson Cancer Center, 2006
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. The primary targets of age-induced atrophy are a relatively rare stromal population. Unfortunately this population is difficult to isolate for a number of reasons, and the mechanisms governing thymic atrophy have remained relatively obscure.
Over the last several years they have devised and implemented a novel computational deconvolution approach to globally and spatially map gene expression in thymic stromal cells, revealing exciting new aspects of thymus biology. Ongoing projects in the lab aim to identify the causes and consequences of age-associated thymic stromal dysfunction. Their ultimate goal is to develop novel approaches to extend the health span during aging.
Awards & Accomplishments
- 2018: HHMI Gilliam Fellowship Mentor
- 2018: Editorial Board: Aging Cell
- 2017: Max and Minnie Tomerlin Voelcker Fund Young Investigator Award.
- 2016: Faculty of the Year, UT Health San Antonio Department of Microbiology, Immunology & Molecular Genetics
- 2015: American Association of Immunologists Early Career Travel Award
- 2015: Greehey President’s Fund for Faculty Excellence Award
- 2014: American Association of Immunologists Travel for Techniques Award
- 2009-2012: Ruth L. Kirschstein National Research Service Award, N.I.H.
- 1998: University of Texas Undergraduate Research Fellowship
American Association of Immunologists
|Yangming Xiao Ph.D. M.D
|Meghan Rueda Ph.D.
Griffith Lab Alumni
- Kymberly Wimberly (M.S.)
- Carolina Cantu (M.S.)
- Stephanie Orozco (M.S.)
- Abdulaziz Almutairi (M.S.)
- Martin Sandoval (M.S.)
- Stephanny Lizarraga (M.S.)
- Chioma Udeaja (M.S.)
- Allison Hester (Ph.D.)
- Sergio Cepeda (Ph.D.)
- Manpreet Semwal (Ph.D.)
- 6/2/21 – Happy Graduation to Allison, Sergio, and Manpreet! They are headed to postdocs at Stanford, UTSW, and Barshop Institute!
- 3/31/21- Congratulations to Manpreet for winning the GSBS 2021 Student Award for Outstanding Student Leadership!
- 2/3/20- Sergio and Manpreet were selected to give podium presentations at AAI 2020 and received AAI Travel Awards!
- 7/26/18 Congratulations, Sergio! A 2018 Howard Hughes Medical Institute Gilliam Fellow!
- Semwal, M.K., Hester, A.K., Xiao, Y., Udeaja, C., Cepeda, S., Verschelde II, J.S., Jones, N., Wedemeyer, S.A., Emtage, S., Wimberly, K., Griffith, A.V. 2022 Redox regulation of autophagy in thymic stromal cells promotes central tolerance. Under Review, Journal of Experimental Medicine
- Hester, A.K., Semwal, M.K., Cepeda, S., Xiao, Y., Rueda, M., Wimberly, K., Venables, T., Dileepan, T., Kraig, E., Griffith, A.V. 2022 Redox regulation of age-associated defects in generation and maintenance of T cell self-tolerance and immunity to foreign antigens. Cell Reports Feb 15; 38 (7): 110363
- Semwal, M.K, Jones, N., Griffith, A.V. 2021 Metabolic Regulation of Thymic Epithelial Cell Function Frontiers in Immunology. March 3; 12:636072.
- Venables, T.*, Griffith, A.V.*, DeAraujo, A., Petrie, H.T. 2019 Dynamic changes in epithelial cell morphology control thymic organ size during atrophy and regeneration. Nature Communications online publication Sep 27, 2019. *These authors contributed equally to this work.
- 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. Jan 30; 22 (5):1276-1287.
- Cepeda, S, Griffith A.V. 2017 Thymic stromal cells: Roles in atrophy and age-associated dysfunction of the thymus. Experimental Gerontology. May; 105:113-117.
- Griffith A.V., 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. Aug 18; 12 (7):1071-1079.
- Bryson JL, Griffith A.V., 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 A.V., 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 A.V., 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 A.V., 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, Gomez G, Venables-Griffith A, Lambertz I, Flores M, Angel JM, Fuchs-Young R, Richie ER, Conti CJ. 2006 Differential susceptibility to chemically-induced thymic lymphomas in SENCARB and SSIN inbred mice. Mol Carcinog. Jul;45(7):543:8.
- 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.