Biological systems face a fundamental challenge: they must preserve forms and functions over generations while retaining the capacity to evolve. We explore molecular mechanisms that reconcile this paradox. Our work asks how protein folding, self-assembly, cellular stress, and natural genetic variation interact to generate heritable phenotypes. We combine genetics, biochemistry, cell biology, genomics, proteomics, quantitative modeling, and experimental evolution, working in organisms from yeast to African turquoise killifish and human patients while extending our findings from molecules to ecosystems.
Prions and other self-templating protein assemblies can store biological information independently of DNA sequence. We investigate how these conformational states arise, how cells transmit them, and how they alter physiology across generations. Our recent work shows that prion switching among proteins that govern DNA repair and recombination can tune mutation rates and change evolutionary outcomes, including the acquisition of drug resistance.
Representative work
Molecular chaperones connect proteome function to changes in the environment. We study how Hsp90 and related networks reshape the consequences of genetic variants. Nucleotide-resolution mapping approaches we developed have revealed that Hsp90 frequently modifies protein-coding variants that transform signaling networks and, remarkably, has an even greater effect on regulatory variants, providing a mechanistic bridge between stress, cryptic variation, adaptation, and disease.
Representative work
Most traits emerge from many genetic variants acting through molecular networks. We build high-resolution maps that connect naturally occurring DNA variation to protein abundance and organismal fitness. By integrating quantitative genetics with proteomics and genome engineering, we aim to predict phenotypes from genotype and identify the molecular logic of complex heredity.
Representative work
Protein assembly can organize normal biology, but related processes also drive age-associated decline and disease. We study how assembly state, cellular environment, and evolutionary history determine whether aggregation is adaptive, neutral, or toxic—and how cells control transitions among these states.
Representative work
We choose methods to fit the biological question and frequently develop new experimental and analytical frameworks when existing tools cannot resolve the relevant mechanism.
Our work is deeply collaborative, and we welcome scientists whose training expands the questions and methods represented in the lab. Learn about joining the lab
