All cell-types in the human body originated from one embryonic cell. Despite efforts to map the diversity of adult human cells, a mystery in biology is how these varied cell-types initially emerged during human embryonic development. I propose a reductionist approach: can we build cell-types from scratch outside the embryo to learn how they develop? … Continued
In biology, function arises from structure. My research is focusing on understanding the principle and mechanism of biological macromolecules through detailed structural visualizations. Distinct from most of the other structural biologists working with purified macromolecules, I use electron cryotomography (ECT), the highest-resolution cellular imaging technique available, to resolve the native structures and assemblies of macromolecular … Continued
I am interested in monitoring, understanding, and preventing the processes that cause human cancer. Previously, I developed the concept of mutational signatures, which I used to reveal the mutational processes in human cancer. My research is based on developing novel mathematical models, implementing these models into computational tools, and applying these tools to already existing … Continued
My research group studies how cells surveil protein biosynthesis to regulate gene expression and maintain a high-quality proteome. We biochemically rebuild cellular quality control pathways to dissect the mechanisms that detect and respond to problems during protein synthesis by ribosomes. We combine these experimental systems with functional and structural approaches to accomplish two goals. First, … Continued
My laboratory investigates the role of RNA in cellular organization and in neurodegenerative disease. There are currently three active areas of research in my laboratory. One, we are studying how RNA can act as a scaffold for cellular compartmentalization by mediating the assembly of RNA-containing granules. Second, we examine how regulated RNA-DNA interactions contribute to … Continued
Cells are physical as well as biological machines. While synthetic biology has focused on the biological, my lab is working to exploit physical interactions to develop new cell-to-cell signaling mechanisms. Physical interactions have the potential to be more rapid, precise, and species-independent compared to biological mechanisms involving DNA and proteins. We focus on bacteria due … Continued
We are taking innovative approaches to study morphogenesis within a developing organism and to leverage that understanding to develop tools and blueprints for building tissues of defined shape and structure in the lab. We propose to develop approaches to control cell-generated mechanical forces within tissues to dissect how patterns of forces control the fundamental cell … Continued
My laboratory studies the evolution of antibiotic resistance, with the ultimate aim of enabling therapies to forestall or prevent resistance evolution. We aim to ‘play a move ahead’ of antibiotic resistance and discover therapies and control strategies informed by the predictability of microbial evolution. Our research is divided into three cross-informative efforts: 1) Understanding the … Continued
Much of the diversity within and between animal species arises due to sequence differences in the vast noncoding regions of the genome. These regions are not transcribed to produce proteins, but rather interact with one another to regulate just which proteins a cell expresses and how much of each it uses. The biophysical mechanisms underlying … Continued
T cell-based immunotherapies have begun to transform how we treat cancer, but are only sometimes effective and can cause serious adverse events. My research group combines mechanistic immunology and protein engineering with the goal of engineering the immune system. We develop approaches to create safer, more effective cancer immunotherapies.