Page 27 - Rappaport Institute Magazine 2024

IMMUNOLOGY
24-25
Homeostasis of B lymphocyte
The broad focus of the Melamed lab is the elucidation of mechanisms regulating generation of B lymphocytes and controlling their fate decisions. B-cell homeostasis and aging – B cell homeostasis is most critical to maintain competence of the immune system. This homeostasis dramatically changes with aging resulting in poor responsiveness to new or evolving pathogens, and reduced efficacy of vaccination. Studies in the lab investigate molecular mechanisms controlling B cell homeostasis and exploring novel approaches for rejuvenating the immune system in aging. microRNA- dependent mechanisms controlling B cell fate decisions. Understanding mechanisms controlling fate decisions of B lymphocytes is critical to treat autoimmunity and cancer. Intracellular signals generated by the B cell antigen receptor (BCR) are most important to determine B cell fate. Studies in the lab are currently exploring novel intracellular mechanisms that are regulated by microRNAs and control B cell development, differentiation and survival. We further explore how these mechanisms are involved in therapy resistance of B lymphoma cells.
Selected Publications
ˆ Avivi I., Zisman-Rozen S., Naor S., Dai I., Benhamou D., Shahaf G., Tabibian- Keissar H., Rosenthal N., Rakovsky A., Hanna A., Shechter A., Peled E., Benyamini N., Dmitrukha E., Barshack I., Mehr R., and Melamed D. (2019). Depletion of B cells rejuvenates the peripheral B cell compartment but is insufficient to restore immune competence in aging. Aging Cell 6:e12959.
ˆ Hines MJ, Coffre M, Mudianto T, Panduro M, Wigton EJ, Tegla C, Osorio-Vasquez
V, Kageyama R, Benhamou D, Perez O, Bajwa S, McManus MT, Ansel KM, Melamed D, and Koralov SB. (2020). miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling. Cell Rep. 33: 108436.
ˆ Dowery R, Benhamou D, Benchetrit E, Harel O, Nevelsky A, Zisman-Rozen S, Braun- Moscovici Y, Balbir-Gurman A, Avivi I, Shechter A, Berdnik D, Wyss-Coray T, Melamed D. (2021). Peripheral B-cells repress B-cell regeneration in aging through a TNFa/ IGFBP-1/IGF1 immune-endocrine axis. Blood. 2021012428
melamedd@technion.ac.il
Doron Melamed Lab
Doron Melamed, PhD Professor of Immunology
PhD, 1994 – The Hebrew University of Jerusalem, Israel
Regulation of B cell homeostasis by microRNA