(4d) Engineering Multi-Fate, Trackable Cells for Smart Precision Medicine

The Therapeutic Consortia Lab will develop new technologies to engineer multi-fate therapeutic cells that treat various diseases, while also reporting their cellular and molecular processes in the body using ultrasound imaging. Our efforts will spearhead next-generation cellular therapies and transformative imaging techniques, deepening our understanding and highlighting areas for advancement.

My research goal is to develop living medicines from immune cells and commensal microbes into multi-functional communities that produce precise therapeutic biomolecules for treating human diseases. My approach of engineering collective behavior in therapeutic cells will improve productivity through division of labor, enabling engineered cells to specialize in producing therapeutic biomolecules and reporter cells that communicate with devices outside the body. My research program will bring together and train interdisciplinary scientists to 1) develop technologies to engineer multi-fate cells against cancer and bacterial infections, and 2) develop novel methods to noninvasively image biological functions in the body using ultrasound imaging.

Research Experience:

I am uniquely suited to lead my proposed research program. At MIT, I developed the synthetic division of labor (SynDoL) circuit that programs ‘seed’ cells to differentiate into multi-fate communities in situ, mimicking the differentiation architecture of stem cells. The composition of SynDoL differentiation is tunable and scalable, allowing for any number of states at desired relative ratios across various cell types. We have demonstrated SynDoL probiotic bacteria differentiating into communities in tumor-bearing mice. My research group will use SynDoL circuits in immune cells and probiotic microbes to create multi-functional consortia in vivo, which promises to unlock a plethora of therapeutic capabilities.

During my Ph.D. at Caltech, I tackled the challenge of monitoring cells and their gene expression within living organisms. I introduced acoustic reporter genes (ARGs), the first reporter genes for ultrasound. ARGs enable, for the first time, ultrasound imaging of the location and function of human cells and commensal probiotics deep within living organisms. My group will advance this nascent technology to allow multiplexed imaging of multiple immune cells deep in the body at unprecedented resolution. This technology will advance the study of therapeutic cell efficacy and safety while creating tools to discover new biological insights.

Teaching Statement:

Formally trained in Bioengineering, Medical Biophysics, and Nanotechnology Engineering in the Chemical Engineering department at the University of Waterloo, I eagerly anticipate contributing to both undergraduate and graduate curricula. In particular, I am enthusiastic about teaching core topics in thermodynamics, transport phenomena, chemical kinetics, and fluid mechanics, as well as synthetic biology, immunology, and neuroscience, and seminar courses on advances in biotechnology and synthetic biology. The research program in my group is inherently interdisciplinary and will offer a rich environment to train students and postdocs.

Selected Publications (complete list at www.arashfarhadi.com):

1. Farhadi, A., Sigmund, F., Westmeyer, G. G. & Shapiro, M. G. Genetically encodable materials for non-invasive biological imaging. Nature Materials 20, 585–592 (2021).
2. Farhadi, A., Ho, G. H., Sawyer, D. P., Bourdeau, R. W. & Shapiro, M. G. Ultrasound imaging of gene expression in mammalian cells. Science 365, 1469–1475 (2019).
3. 3. Bourdeau, R.W., Lee-Gosselin, A., Lakshmanan, A., Farhadi, A., et al. Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts. Nature 553, 86–90 (2018).