We use quantitative biology to understand how human cells perform and protect basic cellular processes.
We are located in the Lewis-Sigler Institute for Integrative Genomics at Princeton University, a hub of interdisciplinary science.
We seek to build and maintain a collaborative environment that integrates the most exciting advances in cell biology, genomics, computational biology, and computer science.
We are always looking for individuals with expertise in one of these areas and who are fearless about learning the others.
Contact Britt if you are interested in joining the lab.
Cells must coordinate the activity of thousands of factors to develop, grow, and respond to stimuli. Our lab is interested in understanding how such coordination is achieved, especially when cells are faced with deleterious conditions.
DNA repair and gene editing
One of our goals is to functionally map the ‘network’ of factors that maintain genome integrity in human cells. DNA is a fragile molecule and is prone to damage. To protect DNA and the information it encodes, cells have evolved a ‘toolkit’ of repair mechanisms. These can fix many types of broken DNA. From decades of prior work, we know a lot about these mechanisms; however, we lack knowledge of how they work together and what happens when they cannot. Our lab is using high resolution functional genomics to interrogate DNA repair as a cohesive system in the contexts of cancer and genome editing. Our approach allows us to isolate and characterize repair mechanisms that have previously been overlooked or obscured by redundancy.
Gene expression and stress responses
Adaptive stress responses are molecular programs that enable cells to maintain function when faced with problematic conditions (i.e. stress or damage) and support function during change (i.e. differentiation). Problematically, these programs also allow cells to adapt to disease conditions, including those associated with cancer. Our work seeks to understand how regulation of gene expression enables cells to buffer stress and supports both normal and pathological changes to cell state.
To enable our work we build genomics tools that allow us to interrogate gene function in human cells with high resolution. These technologies leverage recent advances in CRISPR-based genetics, single-cell RNA-sequencing, and genetic interaction mapping.
What do genes do?
We are first and foremost a genetics lab. Individual gene function can be inferred by observing what happens to cells when the encoded molecules cannot be made, are made incorrectly, or are made in excess. We use CRISPR-based genomics approaches to measure the effects of such perturbations.
How do genes work together?
The molecules that genes encode do not act in isolation. Rather, they influence each other. They work together, alongside each other, or even against each other! We seek to understand how these complicated relationships enable basic tasks inside human cells. Our technologies allow us to investigate gene function at genome-scale, in high resolution, and without bias.