My lab studies the mechanisms by which protein functions evolve. We do this by phylogenetically reconstructing the histories of ancient proteins and then synthesizing, manipulating, and experimentally characterizing their biological functions and physical properties.
This kind of work is powerful and fun — and possible at all — because we are a diverse group of evolutionary biologists, biochemists, biophysicists, computational biologists, geneticists, and molecular biologists, all working together and freely mingling our expertise, techniques, and ideas.
We address classical and recent questions about the nature of evolutionary processes, such as: How do complex molecular systems evolve? Does evolution proceed by a few large-effect or many small-effect mutations? Does epistasis shape the evolutionary process and make the pathways and outcomes of evolution contingent on chance events? Is evolution reversible? How does the architecture of biological systems shape the evolutionary process? How did evolution produce those architectures in the first place?
Evolutionary analysis can also help address core questions in biochemistry, biophysics, and molecular biology. Why do proteins have the particular architectures that they do? How does that architecture itself evolve? What structural and genetic mechanisms cause functions to differ between members of protein families? How do molecular machines, allostery, and molecular interfaces evolve? Are proteins’ physical properties always optimized for their functions, and if not, why not? Can history explain why particular proteins are subject to interference by particular drugs and pollutants? We have found that detailed reconstruction of proteins’ histories helps us to understand why and how their present-day descendants work as they do today.
Columbia University
New York
Postdoc
2012
Columbia University/ American Museum of Natural History
Ph.D - Biological Sciences
2000
Robustness of Ancestral Sequence Reconstruction to Among-site and Among-lineage Evolutionary Heterogeneity.
Robustness of Ancestral Sequence Reconstruction to Among-site and Among-lineage Evolutionary Heterogeneity. Mol Biol Evol. 2025 Apr 01; 42(4).
PMID: 40203289
Ancient biases in phenotype production drove the functional evolution of a protein family.
Ancient biases in phenotype production drove the functional evolution of a protein family. bioRxiv. 2025 Jan 29.
PMID: 39975351
Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.
Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin. Proc Natl Acad Sci U S A. 2025 Jan 28; 122(4):e2414756122.
PMID: 39847336
Robustness of ancestral sequence reconstruction to among-site evolutionary heterogeneity and epistasis.
Robustness of ancestral sequence reconstruction to among-site evolutionary heterogeneity and epistasis. bioRxiv. 2024 Dec 21.
PMID: 39763774
Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.
Symmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin. bioRxiv. 2024 Dec 13.
PMID: 39091803
On the Analysis of Protein Genetic Architecture: Response to "Protein sequence landscapes are not so simple".
On the Analysis of Protein Genetic Architecture: Response to "Protein sequence landscapes are not so simple". bioRxiv. 2024 Dec 06.
PMID: 39677708
Frequent transitions in self-assembly across the evolution of a central metabolic enzyme.
Frequent transitions in self-assembly across the evolution of a central metabolic enzyme. Nat Commun. 2024 12 03; 15(1):10515.
PMID: 39627196
The simplicity of protein sequence-function relationships.
The simplicity of protein sequence-function relationships. Nat Commun. 2024 Sep 11; 15(1):7953.
PMID: 39261454
Frequent transitions in self-assembly across the evolution of a central metabolic enzyme.
Frequent transitions in self-assembly across the evolution of a central metabolic enzyme. bioRxiv. 2024 Jul 07.
PMID: 39005358
Epistasis facilitates functional evolution in an ancient transcription factor.
Epistasis facilitates functional evolution in an ancient transcription factor. Elife. 2024 May 20; 12.
PMID: 38767330
Steenbock Distinguished Lecturer in Biochemistry
University of Wisconsin
2016
Distinguished Alumni Lectureship
University of Queensland School of Biochemistry
2016
Guggenheim Foundation Fellowship
2014
Hans Falk Award
National Institute for Environmental Health Sciences
2014
Richard Jones Investigator Award
Oregon Medical Research Foundation
2010
Early Career Investigator
Howard Hughes Medical Institute
2009
U.S. Presidential Early Career Award for Scientists and Engineers
2007
Alfred P. Sloan Foundation Research Fellow
2006
CAREER Award
National Science Foundation
2006
Distinguished University Lecturer in Environmental Sustainability
Carnegie-Mellon University
2002