Spatial factors regulating the immune response
Immune responses are typically highly localized and involve small groups or pairs of physically associating cells. In addition, in dense, 3-D tissues, cytokines and other inflammatory mediators often diffuse only over distances of a few cell diameters. These spatial factors generate significant phenotypic and functional heterogeneity among cells within the same organ. A major focus of our lab is in studying how localized, inter-cellular communication regulates the adaptive immune system in the context of acute immune responses and in solid tumors.
Relevant publications:
The Spread of Interferon-γ in Melanomas is Highly Spatially Confined, Driving Non-Genetic Variability in Tumor Cells. Edoardo Centofanti*, Chad Wang*, Sandhya Iyer*, Oleg Krichevsky, Alon Oyler-Yaniv, and Jennifer Oyler-Yaniv, 2023. PNAS. 120 (35) e2304190120.
A tunable diffusion-consumption mechanism allows plasticity in cell-to-cell communication in the immune system. Alon Oyler-Yaniv, Jennifer Oyler-Yaniv, Benjamin M. Whitlock, Zhiduo Liu, Ronald N. Germain, Morgan Huse, Grégoire Altan-Bonnet, and Oleg Krichevsky, 2017 Immunity, 46, 4, 609-620.
Host-viral control of the cell death decision
Programmed cell death is one of the most basic and evolutionary conserved forms of defense against intracellular pathogens like viruses. The logic is simple: if the host cell dies before the virus completes its lifecycle, the virus cannot spread. Consequently, viruses and other pathogens have evolved myriad mechanisms to antagonize cell death. We are investigating how the host keeps this defense mechanism intact - despite viral interference - by encoding redundancy in the design and topology of the larger cell death signaling network. In parallel, we are working on ways to rationally manipulate the cell death decision in the context of cancer immunotherapy and viral infection.
Relevant publications:
TNF controls a speed-accuracy tradeoff in apoptotic decision to restrict viral spread. Jennifer Oyler- Yaniv*, Alon Oyler-Yaniv*, Evan Maltz, and Roy Wollman, 2021 Nat. Comms. 12, 2992.