Questions that drive us.
How do you define yourself (... a cell)?
How do you define yourself? What data is that based on? I could define myself by many different factors including my ancestry ("genotype"), appearance ("phenotype"), home ("origin"), or what I produce ("secrete"). So it would be safe to say what we measure matters.
Even one parameter I could analyze a number of different ways. I could quantitate how much time I spend doing different activities and call myself "a sleeper," or I could analyze how I have changed over time in my career "trajectory," or I could consolidate many parameters and determine most "differentially enriched" between me and others, or even how much I enjoy chocolate. So it would be safe to say how we analyze matters.
Spatial Systems Biology Technologies for Cellular Engineering.
Similarly how we measure, analyze, and define cells in our body is critical to understanding how they work.
We think of our tissues as a multi-tiered set of interacting systems of network interactions. Take cancer for instance: Underlying the larger "bulk" cancer tissue is a set of cells that work together to form functional tissue units or "cellular neighborhoods" such as vasculature or immune-enriched stroma. Underlying these conserved multicell modules are individual cell-cell interactions coordinated by membrane-bound and soluble molecules. An individual cell has a further intracellular network of these molecules that controls cell type, fate, and function.
Questions That Excite Us.
We are driven both by curiosity to how these networks are coordinated across length scales and also towards the goal ability to control multi-cell organization within tissues. We aim to answer broad and basic questions like:
Are there cells that are primary drivers of tissue organization?
What is a cell's capacity to rearrange or maintain its microenvironment?
How can we control a cell's capacity to rearrange or maintain its microenvironment?
Can we use this to reverse cellular disorder we observe in disease tissue like cancer?
To address these questions, we work at the interface of engineering and immunology, utilizing and developing systems immunology tools to investigate tissue structure in situ. Our approach begins with the application of multiplexed imaging and computational techniques to characterize spatial cellular responses related to the effectiveness of anti-cancer cell therapies. Subsequently, we implement cell therapies or biomaterial augmentations to manipulate the cellular microenvironment, creating a virtuous cycle of experimentation and refinement.
Projects.
Based on this we have numerous projects ongoing, but some that are particular pillars of the lab include:
