We are pleased to announce that Dr. Takis Benos and the Benos lab have been awarded an NIH R01 grant entitled “COPD subtypes and early prediction using integrative probabilistic graphical models”. This is a 4-year award that will which is expected to provide $3.23 million in total support to their research aiming to identify subtypes of chronic obstructive pulmonary disease (COPD).
COPD is the 3rd leading cause of death worldwide. In 2019 it was responsible for 3.23 million deaths. In USA, it kills ~37 people / 100,000 per year. One of the problems with this disease is that it is heterogeneous and identifying subtypes can help improve disease management and treatment.
And additional congratulations to Dr. Takis Benos and his colleague Dr. Peter Spirtes of the Carnegie Mellon University Department of Philosophy has been awarded an RO1 entitled “Interpretable graphical models for large multi-modal COPD data” which focuses on developing causal graphical models for any-type of data and apply them to address important questions in COPD research.
A myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IkB kinase (IKK) complex is an integration hub for cytokines that govern nuclear factor kB (NF-kB) signaling. In response to inflammation, IKK is activated through recruitment to receptor-associated protein assemblies. How and what information IKK complexes transmit about the milieu are open questions. In this paper, the Lee Lab track dynamics of IKK complexes and nuclear NF-kB to identify upstream signaling features that determine same-cell responses. Experiments and modeling of single complexes reveal their size, number, and timing relays cytokine-specific control over shared signaling mechanisms with feedback regulation that is independent of transcription. Their results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables cytokine-specific regulation and parsimonious information transfer. They propose that emergent properties of stochastic pooling are general principles of receptor signaling that have evolved for constructive information transmission in noisy molecular environments.
Cruz JA*, Mokashi CS*, Kowalczyk GJ, Guo Y, Zhang Q, Gupta S, Schipper DL, Smeal SW, Lee REC. A variable-gain stochastic pooling motif mediates information transfer from receptor assemblies into NF-kB. Sci. Adv. 7, eabi9410 (2021)