The Iyengar laboratory is focused on understanding how signals are routed and processed through cellular signaling networks including mechanisms of information sorting and integration in the context of cell and tissue level functions.

We are interested in understanding dynamics of network topology. For this we focus on identifying regulatory motifs such as feedback and feedforward loops and determining their information processing capability. We have constructed and analyzed dynamic maps of these motifs to understand how cellular signaling networks engage the various cellular machinery to produce physiological responses to extra-cellular signals. To study complex cell signaling networks we utilize a combination of experimental and theoretical approaches. Multidimensional experimental approaches currently being used in the laboratory proteomics, bulk transcriptomics and single cell RNA-seq and mRNA profiling by sequencing. These experimental approaches are being integrated with theoretical analysis using both graph theory approaches differential equation based modeling to understand network regulation of cell proliferation and activity induced synaptic plasticity and physiological function.

We are interested in understanding how spatial organization within cells and tissues contributes to dynamic stability. We are studying the role of cell shape in regulating information processing within signaling networks. For these studies at the experimental level we are using approaches to observe and quantify biochemical signaling reactions in live cells. We are also using patterned surfaces at the nano and microscale as to obtain cells of specific shapes that can be imaged. To decipher the information content in cell shape we are analyzing signaling networks using partial differential equations. We are developing spatially realistic models of signaling networks to understand the origins and dynamics of microdomains of signaling components. We are also interested in understanding the dynamics underlying tissue integrity. We are using spatial transcriptomic data to develop multi-scale models as well to determine if dynamic loops that integrates signaling networks in multiple cell types forms the basis for tissue integrity and physiological function.

We are developing systems level approaches to understanding drug action at a genome-wide level. We are constructing large scale networks to capture all of the known protein-protein interactions in the human genome to computationally identify selective regions (disease neighborhood) within the interaction space associated with specific diseases. We are analyzing the relationship between drug targets and other cellular components to understand the relationship between disease neighborhood and targets of drugs used to treat the disease. From such analyses we are attempting to predict adverse events and explain adverse events reports in the FDA–AERS database.

For more information, please visit the Iyengar Laboratory, Systems Pharmacology and Systems Biology website.

Computational Biophysics & Systems Pharmacology Team

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