Assistant Professor, School of Biomedical Engineering

 

Cell competition has been suggested to safeguard the health of tissues, acting as a surveillance mechanism against abnormal cells by allowing “fitter” cells to eliminate their weaker neighbours – indeed, Darwin’s theory of “survival of the fittest” applies at the cellular level. However, the genetic rules that govern cell fitness are largely unknown. Dr. Shakiba’s lab is interested in uncovering (reverse engineering) and programming (forward engineering) these rules in order to answer fundamental biological questions and give rise to a novel class of engineered stem cell therapies for regenerative medicine applications.

Using cell competition to understand stem cell systems
The Shakiba lab uses cell competition as a novel lens to understand the dynamics of multicellular stem cell systems. Using a combined cellular barcoding and mathematical modeling approach to uncover how a balance between cell competition and co-operation leads to the ultimate success or peril of cell populations, projects in the Shakiba lab shed new light on embryonic development, stem cell lineage commitment, tissue regeneration, and disease. To reverse engineer the genetic rules that govern cell fitness in these stem cell systems, the Shakiba lab uses a systems biology approach combining CRISPR gRNA libraries with quantitative measurements of single cell dynamics.

A novel class of engineered stem cell therapies using synthetic biology
To forward engineer the fitness of stem cells and their derivatives, the Shakiba Lab develops synthetic genetic circuits that rely on feedback/feedforward motifs to precisely control the expression of key fitness genes. Steered by computational models that map the expression of key genes to cell fitness, the Shakiba Lab is developing a novel class of engineered stem cells with customizable competition potential. These efforts will contribute to key improvements in the efficiency of cell therapy manufacturing while enhancing the clinical efficacy of cell therapies and engineered tissues.

For more information about Dr. Shakiba’s work, visit Google Scholar.