Research

Mission statement: We aim to understand how the atomic structures of protein assemblies govern their biological function. We use cryo-electron microscopy (cryo-EM) to determine three-dimensional protein structures and biochemical and cellular approaches to study their function. We focus on proteins involved in human disease, and we harness the insights to develop strategies for pharmacological intervention. Broadly, we aim to connect protein structure to function (and dysfunction), to understand the complex roles they play in cells, and to use the insights for developing novel therapeutics to treat human diseases.

Methods: To understand the molecular basis for how protein assemblies work, we collectively utilize a wide variety of techniques. At the core of our work is cryo-electron microscopy (cryo-EM), which enables imaging protein samples frozen in their native hydrated states using an electron microscope. We employ cryo-EM techniques to directly image protein samples, isolated from cells and/or in their native cellular environment. Computational approaches help to make sense of and interpret the cryo-EM data to gain structural insight. We are also actively involved in methodology development to advance these aims. Of central importance to imaging proteins is the ability to isolate, purify, and characterize the specimens, and also to probe function. To this end, we employ a wide variety of techniques in biochemistry, biophysics, molecular and cell biology. In some cases, structures also provide atomic level blueprints for therapeutic design. We have ongoing collaborations with computational and chemistry groups who help develop and assay small molecule inhibitors, which can modulate protein function. These techniques are often employed iteratively within the scope of a research project to broadly understand both structure and function.

Implications: Protein function and dysfunction underlies the majority of human diseases. While the core mission of the lab is to understand how they work, there is often direct relevance to human health. We focus on proteins involved in HIV infection and in those that play key roles in cancer. Ultimately, our goal is to establish a basic biological understanding of protein function. In some instances, we also have the opportunity to translate our findings in the laboratory to design therapeutics and to harness the information to directly improve human health.

Projects: Science is a process … for every question answered, more arise. Interests build on unexpected findings, spark, develop, transform, and sometimes diverge. Occasionally, we are beat to the punch and have to rethink specific aims. And let’s be honest, other times we are quite simply at the whim of our funders. For a list of ongoing projects, please have a look at our most recent publications. For more specifics, please contact the boss.