(6iq) Synthetic Post-Translational Circuits for Cell-Mediated Therapy of Diseases Involving Immune Dysfunction

My doctoral research was completed with Dr. Josh Leonard in the Department of Chemical and Biological Engineering at Northwestern University. During this time, I applied synthetic biology tools to study the structure-function relationships of native receptors as well as developed synthetic receptors that drive expression of a gene of interest in response to extracellular proteins. Using this system, which was the first synthetic receptor able to detect and respond to soluble extracellular ligands, we demonstrated secretion of IL-2, a proinflammatory cytokine, in response to VEGF, an anti-inflammatory cytokine, in T cells.

I am currently a postdoctoral researcher with Dr. Jim Collins in the Institute for Medical Engineering and Science at MIT where I developed a novel platform for synthetic post-translational circuits in mammalian cells. This research is the first synthetic circuit that uses post-translational modifications similar to but completely independent from native signaling pathways. Unlike other synthetic circuits, signals are transduced by the same phosphorylation-based mechanism as native signaling pathways, which enables the same fast and layered response that facilitates tighter control of cellular responses and more flexible outputs. When connected upstream to synthetic receptors, engineered signaling pathways can be configured to sense and respond to changes in extracellular ligand concentration. These circuits are completely orthogonal but can be easily integrated with native signaling pathways. They are also modular and tunable, which allows for the same full range of outputs as native signaling pathways.

My lab will specialize in developing and utilizing synthetic post-translational circuits to better understand and treat diseases such as cancer that are associated with immune dysfunction.

Research objective 1 – Develop and utilize post-translational circuits to study in vivo dynamics within tumor cells and the tumor microenvironment as the tumor is established, grows, and metastasizes. The speed, sensitivity, and reversibility of synthetic post-translational circuits will enable real-time measurements of dynamics within the tumor, including the levels and types of cytokines in the tumor microenvironment as well as the activation of key signaling pathways within both cancer cells and tumor-associated immune cells.

Research objective 2 - Develop post-translational circuits that integrate input from the tumor microenvironment and transduce the signal into therapeutically beneficial responses. Outputs will include activation or inhibition of native signaling pathways and the secretion of proinflammatory cytokines to stimulate the immune system.

Research objective 3 - Develop novel platforms for targeted inducible control of mechanisms similar to post-translational modifications found in natural biological systems, such as methylation, acetylation, and ubiquitination. This will enable faster and finer control over cellular responses, such as the regulation of gene expression, RNA processing, and protein function.

My past experience in developing post-translational circuits makes me uniquely qualified for this innovative research, which has the potential for groundbreaking developments in both synthetic biology and cell-mediated therapy. By employing the same types of post-translational modifications that regulate cellular behavior in nature, we open the door to a larger array of methods to enable tighter and faster control, more closely resembling the many levels of regulation that exist in the mammalian cell. This work will help to elucidate the complicated mechanisms by which cells transduce information and drive the development of safer and more effective cell-mediated therapies for disease treatment.

Teaching Interests:

I am comfortable teaching a wide range of classes at any educational level including any of the core chemical engineering courses or biology-related electives. I am also excited about developing a new class on synthetic biology that will cover the basic techniques and technologies in synthetic biology then move on to real-world topics including applications, safety, and ethics. This class will emphasize written and oral communication.