Shawn O. Pearce

Shawn O. Pearce is an American molecular biologist and geneticist known for work on DNA repair, homologous recombination, and structural mechanisms of recombination enzymes. Pearce has held research and faculty positions at major biomedical institutions and collaborated with investigators from universities and research institutes worldwide. His work bridges biochemistry, structural biology, and translational genomics, influencing research in cancer biology, bacteriophage biology, and gene-editing technologies.

Early life and education

Pearce was born in the United States and raised in a family engaged with science and medicine, developing early interests in biochemistry and molecular genetics through exposure to laboratories at Stanford University and summer programs associated with Cold Spring Harbor Laboratory. He completed undergraduate studies in biochemistry at the Massachusetts Institute of Technology where mentors included faculty from the Whitehead Institute and collaborators connected to the Howard Hughes Medical Institute. For graduate training Pearce attended Harvard Medical School and its affiliated research hospitals, conducting doctoral research on DNA recombination with faculty linked to the National Institutes of Health and the Broad Institute. During postdoctoral training he worked at institutions including the University of Washington and the Fred Hutchinson Cancer Research Center, collaborating with investigators from Salk Institute for Biological Studies, University of California, Berkeley, and Columbia University.

Research and career

Pearce established an independent laboratory focusing on mechanistic studies of DNA double-strand break repair, homologous recombination, and the enzymology of recombinases and nucleases. His lab partnered with structural groups at Max Planck Institute of Biochemistry, European Molecular Biology Laboratory, and Weizmann Institute of Science to combine cryo-electron microscopy, X-ray crystallography, and single-molecule fluorescence approaches. He maintained collaborative ties with translational teams at Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, and Johns Hopkins University School of Medicine to evaluate implications for cancer therapy and synthetic biology. Pearce served on study sections for the National Science Foundation and the National Institutes of Health, and participated in international consortia with members from Cold Spring Harbor Laboratory, Imperial College London, University of Cambridge, and ETH Zurich.

Major contributions and discoveries

Pearce contributed to characterization of the biochemical activities and structural conformations of recombinase proteins related to RecA and Rad51, clarifying the ATP-dependent strand-exchange cycle and mediator protein interactions. He published studies dissecting the coordination between helicases such as BLM helicase and nucleases like MRE11 in end-resection pathways, linking these mechanisms to genomic stability in models used at Fred Hutchinson Cancer Research Center and Broad Institute. Pearce’s laboratory identified novel protein complexes that modulate non-homologous end joining and microhomology-mediated repair, informing therapeutic strategies pursued at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. His collaborations revealed structural snapshots of recombination intermediates using cryo-EM facilities at European Molecular Biology Laboratory and Max Planck Institute, providing atomic models referenced alongside structures from Scripps Research and Ragon Institute. Pearce also investigated phage-encoded recombination systems, connecting his findings to studies on CRISPR-Cas9 off-target effects and gene-editing fidelity with partners at the Broad Institute and Harvard University.

Awards and honors

Pearce received recognition including career development awards from the National Institutes of Health and investigator awards from foundations allied with the Howard Hughes Medical Institute network. He was invited to present keynote talks at meetings organized by Cold Spring Harbor Laboratory, Gordon Research Conferences, and the American Society for Cell Biology. Professional honors included election to leadership roles in committees of the American Society for Biochemistry and Molecular Biology and advisory appointments to consortia at the European Molecular Biology Organization. He was named a fellow of collegiate scientific societies associated with Massachusetts Institute of Technology alumni and awarded institutional prizes for translational impact by Fred Hutchinson Cancer Research Center.

Selected publications and patents

Selected peer-reviewed publications and patent filings associated with Pearce’s work include mechanistic and structural studies of recombination enzymes, repair-pathway modulation, and gene-editing accuracy. Representative articles appeared in journals such as Nature, Science, Cell, Nature Communications, and Proceedings of the National Academy of Sciences. Key publication topics covered ATPase cycles of recombinases, cryo-EM structures of recombination intermediates, coordination of helicase-nuclease activities in end resection, and biochemical determinants of non-homologous end joining specificity. Pearce is named on patents related to modulation of DNA repair pathways for therapeutic use and improved genome-editing enzymes; these filings list co-inventors and assignees associated with institutions like the Broad Institute, University of Washington, and industrial partners in biotechnology incubators.

Category:American molecular biologists Category:Geneticists