Iyad Sayed Issa

Iyad in the lab

Iyad Sayed Issa ‘27

(he/him)

Home Department: Molecular, Cellular, and Developmental Biology (Miller-Jensen Lab) 

Research Project: Discovery and Characterization of Transcription Factor Networks that Tune Macrophage Functional Heterogeneity

Macrophages are innate immune cells that exist in almost every tissue in the body. They defend against infections, contribute to tissue repair, and maintain tissue homeostasis. Macrophages can be classified as pro-inflammatory (M1) or anti-inflammatory (M2) based on stimulus. However, in tissues, macrophages encounter multiple stimuli and thus are highly heterogeneous, displaying both M1 and M2 functional characteristics. There is a limited understanding of how heterogeneity in macrophage states is regulated. The objective of my thesis project is to identify and modulate transcription factor networks that regulate macrophage heterogeneity and the balance of M1 versus M2 functions. We hypothesize that negative cross-regulation between transcription factors controls macrophage heterogeneity and leads to M1-like versus M2-like subsets.

Relevant Publications

Alexander, A.F., Kelsey, I.A., Forbes, H., Miller-Jensen, K. (2021). Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-mediated inflammatory response

Bass, V.L., Wong, V.C., Bullock, M.E., Gaudet, S., Miller-Jensen K (2021). TNF primarily modulates transcriptional burst size of NF-kB-regulated genes

Muñoz-Rojas, A.R., Kelsey, I., Peppalardo, J., Chen, M., Miller-Jensen, K. (2021). Cross-talk between opposing macrophage polarization cues leads to individual cells exhibiting orthogonal secretion programs following co-stimulation

Schematic of cell reactions to IL4 and LPS IFN gamma

Schematic depicting how co-stimulation could lead to either mixed responses or specialized responses in individual macrophages (Muñoz-Rojas et al., 2021)