Lee Lab Publishes in Science Advances

 

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)

NSF Graduate Research Fellowship Program offers awards to Caroline Larkin, April Rich and Gaby Gerlach

The 2021 NSF Graduate Research Fellowship Program (GRFP) has offered awards to Caroline Larkin (Faeder/Shoemaker Labs) and April Rich (Carvunis Lab), while Gaby Gerlach (Camacho Lab) has received an honorable mention. Congratulations!

Caroline Larkin April Rich Gaby Gerlach

About the NSF Graduate Research Fellowship Program: The purpose of the NSF Graduate Research Fellowship Program (GRFP) is to help ensure the quality, vitality, and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing full-time research-based master’s and doctoral degrees in science, technology, engineering, and mathematics (STEM) or in STEM education.

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Samantha Furman awarded NIH NCI fellowship

Samantha Furman awarded NIH NCI F31 Ruth L. Kirschstein Predoctoral National Research Service Award to support her PhD work titled “Quantifying heterocellular communication and spatial intratumoral heterogeneity from high dimensional spatial proteomics data”

Tumors are dynamic ecosystems comprising spatially heterogeneous microdomains. Microdomain-specific signaling networks reciprocally support a phenotypic continuum with complex intermediary cell types and cell states shaping the tumor microenvironment. The recent explosion of next-generation, high-content, high-throughput spatial imaging technologies for intact tissues measuring protein expressions, DNA and RNA probes has provided an opportunity to harness spatial data for inferring tumor biology. The overarching goal of this proposed computational and systems pathology project is to identify the emergent pathogenic cellular and molecular network transitions within an evolving tumor microenvironment from hyperplexed spatial image datasets associated with disease progression through cellular phenotyping, microdomain extraction, and spatial network biology inference algorithms. In combination, these methods have the potential to provide insights into pathophysiological mechanisms, identify novel drug targets and inform therapeutic strategies for individual patients.
Samantha Furman is a 4th year PhD student in Dr. S. Chakra Chennubhotla’s lab in the Computational and Systems Biology Department. With this fellowship support, Samantha will continue her training towards a PhD in Computational Biology from the University of Pittsburgh.

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