Laboratory of Systems Biology and Quantitative Pharmacology

Welcome to the Fallahi-Sichani Lab
Department of Biomedical Engineering
University of Virginia

The systems biology research in the Fallahi-Sichani lab is focused primarily on understanding the mechanisms through which human cells respond heterogeneously to environmental and therapeutic perturbations. Such responses can take the form of changes in gene expression, metabolic state, or cell fate decisions such as differentiation, cell division, growth arrest, or induction of cell death in response to therapeutic perturbations (e.g., cancer drugs). Interestingly, these responses vary among distinct cell types, or even among populations of genetically identical cells exposed to uniform conditions. Understanding the mechanisms that underpin heterogeneous cell fate decisions and cellular plasticity has been a key challenge for quantitative biology and precision medicine. The challenge is significant because biomolecules in cells do not act in isolation but are embedded in multi-component networks that are subject to homeostatic control. Uncovering the rules that govern such seemingly complex networks and how they vary from one cell to the next would be difficult, if not impossible, using conventional methods. In our laboratory, we have developed and used a combination of experimental, analytical, and computational tools to assay these sorts of networks and interrogate their complexities. What makes our transdisciplinary approach unique is its focus on: (1) the innovative deployment of cutting-edge, high-throughput, multiplexed technologies to generate hypothesis-driven datasets of single-cell and population responses to signaling perturbations (across various isogenic and genetically distinct contexts), (2) the application of modern computational tools to analyze such high-dimensional datasets, and (3) the creation of quantitative models of cellular response that are predictive at single-cell, molecular and network levels. The iterative use of experimental and modeling methods has enabled us to discover novel mechanisms of cellular signaling, plasticity and heterogeneity in response to perturbations, validate these mechanisms, and utilize them to guide the development of better therapies for precision medicine.