Nearly 50% of the human genome consists of thousands of nearly identical copies of mobile elements and ancient retroviruses called Transposable Elements (TEs). Epigenetically silenced in all adult cells, TEs are paradoxically reactivated during early embryonic development. Our recent findings reveal that TE reactivation is regulated and essential for mammalian development. Notably, TEs are unintentionally … Continued
Metal-containing enzymes (metalloenzymes) hold tremendous promise for sustainable chemistry because they perform challenging reactions under mild conditions. However, known metalloenzymes are limited in substrate scope or have complicated structures that are recalcitrant to engineering, which poses a major constraint on biocatalyst development. Excitingly, microbial genomes harbor a wealth of unexplored enzymes that can serve as … Continued
Eukaryotic messenger RNAs (mRNAs) are extensively chemically modified to create non-canonical bases that can impact their fate and function in cells. The full collection of RNA modifications in cellular mRNAs, the epitranscriptome, represents a previously unappreciated layer of gene regulation. RNA modifications clearly have an important role in health and disease; many RNA modifying enzymes … Continued
Post-translational modifications (PTMs) control the structure, activity, localization, and lifetime of nearly all proteins and are often dysregulated in human disease. Identification of PTMs has far outpaced assignment of their biological functions, an endeavor that requires proteome-scale information about where and when these modifications occur within the cell that is unobtainable with current technologies. To … Continued
My lab is taking a reverse-engineering approach to understand how cells move through, interact with and respond to their environment to perform complex and essential behaviors. We treat behavior as the output of a microscopic robot driven by patterns of signaling activity acting on a common molecular toolbox. We are developing new methods to extract … Continued
A protein is a dynamic shape-shifter whose function is determined by the set of different structures it adopts. Unfortunately, it is impossible to directly observe most of these structures. Our lab combines computer simulations and biophysical experiments to build quantitative maps of the different shapes a protein adopts, understand the functional implications of this conformational … Continued
The long-term goals in our research group are to understand how protein conformational ensembles are reshaped by perturbations and to quantify how these perturbations impact protein function and organismal fitness. To accomplish these goals, our group creates new computational and biophysical approaches to study how proteins move between different conformational states. A primary guiding principle … Continued
I research how the cytoskeleton gives cells their shape, positions organelles, moves materials, and divides cells. I use biochemical and engineering approaches to uncover the mechanisms that generate its architecture. My research reveals how cellular structures are built and how malfunctions occur, which lie at the heart of many diseases involving cell proliferation and cancer.
Our lab studies mechanisms underlying gene regulation by non-protein-coding RNAs (ncRNAs). Many RNAs are transcribed but have functions other than to translate the sequence information to proteins. To fulfill a specific role, each RNA has a unique combination of sequence and structure. A major effort in the laboratory is to uncover how structures govern RNA … Continued
My laboratory’s long-term research interest is to elucidate cellular mechanisms that govern chromosome inheritance and integrity, with a combination of cell biological, biochemical, and biophysical methods. In particular, our research program aims to understand the execution, interplay, and coordination of DNA replication and repair, sister-chromatid cohesion, and chromosome segregation during the cell cycle. Uneven distribution … Continued