Current advisor: Takeshi Egawa, MD, PhD
Undergraduate university: University of Montana
In acute infections/vaccinations, significant proportions of effector T cells are derived directly from naive cells, and the subsequent death of short-lived effector T cells (Teff) quickly re-establishes immune homeostasis. However, when the pathogen persists for a long time, such as in chronic viral infections or in tumors, T cell response must be sustained for longer duration. Given the short-lived, terminally differentiated feature of Teff cells, it remains unknown how Teff population is sustained in the presence of chronic antigens. The goal of my thesis work is to understand how productive CD8 and CD4 T cell response is sustained at the cellular levels and molecular levels using a chronic viral model. For CD8 T cells, we discovered a CX3CR1+ CD8 population that contains a TIM3+ subpopulation that is highly proliferative and carry effector functions, and a TIM3– subpopulation that serves as an intermediate progenitor that gives rise to TIM3+ subpopulation. For CD4 T cells, I identified a Bcl6-dependent progenitor CD4 population that gives rise to both BCL6–BLIMP1+ effector cells and CXCR5+ TFH cells.
Xia Y, Sandor K, Pai JA, Daniel B, Raju S, Wu R, Hsiung S, Qi Y, Yangdon T, Okamoto M, Chou C, Hiam-Galvez KJ, Schreiber RD, Murphy KM, Satpathy AT, Egawa T. 2022 BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4+ T cell responses to persistent antigen. Immunity, epub ahead of print():.
Raju S, Xia Y, Daniel B, Yost KE, Bradshaw E, Tonc E, Verbaro DJ, Kometani K, Yokoyama WM, Kurosaki T, Satpathy AT, Egawa T. 2021 Identification of a T-bet hi Quiescent Exhausted CD8 T Cell Subpopulation That Can Differentiate into TIM3 + CX3CR1 + Effectors and Memory-like Cells. J Immunol, 206(12):2924-36.
Tonc E, Takeuchi Y, Chou C, Xia Y, Holmgren M, Fujii C, Raju S, Chang GS, Iwamoto M, Egawa T. 2021 Unexpected suppression of tumorigenesis by c-MYC via TFAP4-dependent restriction of stemness in B lymphocytes. Blood, 138(24):2526-38.
Huang X, Ferris ST, Kim S, Choudhary MNK, Belk JA, Fan C, Qi Y, Sudan R, Xia Y, Desai P, Chen J, Ly N, Shi Q, Bagadia P, Liu T, Guilliams M, Egawa T, Colonna M, Diamond MS, Murphy TL, Satpathy AT, Wang T, Murphy KM. 2021 Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis. Immunity, 54(7):1417-1432.e7.
Bartleson JM, Viehmann Milam AA, Donermeyer DL, Horvath S, Xia Y, Egawa T, Allen PM. 2020 Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions. Nat Immunol, ():Online ahead of print.