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.
To understand the molecular bases for how proteins and protein assemblies work, we utilize a variety of techniques. At the core of our work is cryo-electron microscopy (cryo-EM), a technique that enables imaging protein specimens frozen in their native hydrated states. We employ cryo-EM methods to directly image protein specimens, which establishes the raw data that we use to make sense of protein structure and function.
Computational approaches help to make sense of and interpret the cryo-EM data to obtain atomic-level insights into protein structure and organization. We are also actively involved in methodology development to advance computational tools. Of central importance to imaging protein specimens is the ability to isolate, purify, and characterize the samples, and also to probe function. To this end, we employ a variety of techniques in biochemistry, biophysics, molecular and cell biology, which complement the structural findings to gain mechanistic insight into function.
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 directly bind to proteins and alter or inhibit their function. These techniques are often employed iteratively within the scope of a research project to understand how protein function can be modulated by small molecules, to gain insights into protein evolution and development of resistance to the small molecules, and to help design novel therapeutics.
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 on 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 insights to improve human health.
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.