[Dec. 2] 118th IRCMS Seminar

November 4 2024

We would like to inform you that the 118th IRCMS seminar has been scheduled as below.
* This IRCMS seminar is open to everyone.

Date      : December 2, 2024 (Monday)

Time      : 16:00-17:00

ZOOM　: Meeting ID: 947 2762 2634
            　 Passcode: ircmsSem12

Speaker : Dr. Takeshi Egawa (Washington University School of Medicine)

Title        : Lymphocyte Proliferation and Differentiation, Insights into lymphomagenesis and T cell Exhaustion

Abstract 

Lymphocytes are capable of robust expansion upon antigen receptor stimulation and are one of the most rapidly dividing cells in postnatal organisms. Such robust proliferative capacity is critical for establishing broad antigen receptor repertoires during development and for quantitatively amplifying antigen-specific immunity upon pathogen invasion. However, like many other primary cells, they have limited proliferative capacity as expanding lymphocytes undergo terminal differentiation with transient functionality at the expense of their longevity. Such transition of an undifferentiated progenitor cell to more mature states following a proliferative burst is seen at several checkpoints during the development of lymphocytes as well as other cell types. We predict that such cell differentiation or loss of the progenitor states is a process controlled by gene regulatory circuitry closely associated with rapid cell proliferation although the molecular basis remains undefined. Furthermore, the maintenance of population dynamics rather than the size of each population, by generating newly differentiated cells, may be fundamental for sustaining functionality of a specific cell population. We have been studying the biological significance of the tight coupling of the restriction of cell stemness with cell proliferation, potential manipulation to overcome the restriction, and consequences of perturbed population turnover in lymphocytes. I will discuss these questions in the context of gene regulatory networks initiated by the transcription factor c-MYC, tumor suppression and T cell exhaustion.

2-3 major papers:

2-3 major papers:

1. Tonc E, Takeuchi Y, Chou C, Xia Y, Holmgren M, Fujii C, Raju S, Chang GS, Iwamoto M, Egawa T: Unexpected suppression of tumorigenesis by c-MYC via TFAP4-dependent restriction of stemness in B lymphocytes. Blood, 2021, 138: 2526-2538. doi: 10.1182/blood.2021011711. PMID: 34283887. PMCID: PMC8678995.

2. Daniel B*, Yost KE*, Hsiung S*, Sandor K, Xia Y, Qi Y, Hiam-Galvez KJ, Black M, Raposo C, Shi Q, Meier SL, Belk JA, Giles JR, Wherry EJ, Chang HY**, Egawa T**, Satpathy AT**. (*co-first authors, **co-senior authors). Divergent clonal differentiation trajectories of T cell exhaustion. Nat Immunol, 2022, 23: 1614-1627. doi: 10.1038/s41590-022-01337-5. PMID: 36289450.

3. Hsiung S, Raju S, Liu TT, Raposo CJ, Murphy MK, Wang Z, Satpathy AT, Murphy KM, Egawa T: Cell competition protects CD8 + T cells from terminal exhaustion, Manuscript under revision.

Flyer: (Click to enlarge)