Human cells process vast amounts of environmental information to generate sophisticated responses such as movement, growth and differentiation. Such decisions are made by complex networks of signaling proteins in coordination with nuclear transcription factors that bind DNA. One of the most challenging problems in biomedical engineering is understanding how these networks of proteins act to carry out these remarkable behaviors.

Much evidence suggest that complex signaling systems can be understood, in part, through the framework of modularity and hierarchical organization, akin to digital circuit modules in electronics that carry out elemental processing functions. Developmental biologists have perturbed genes one by one to identify key nodes of these circuit modules. In many diseases, clinicians have observed the clustering of genomic or epigenomic alterations in key nodes of these circuit modules. Thus, the new tools of perturbing signaling processes and the human genome provide new opportunities to understand and control the circuits underpinning development and human disease. Dr. Saha’s lab is using a variety of approaches to ask the following general questions:

Can we engineer cells with new, useful behaviors for therapy?
Can we engineer the cell’s microenvironment to produce cells with new, useful behaviors for therapy?
How do molecular signaling systems in human cells program complex cellular behaviors?
How do signaling networks evolve?
How do these networks robustly program complex spatial/​temporal responses?
Can we systematically build new signaling circuits or modify cellular behavior?