Seth Shipman and his team develop innovative strategies to manipulate cells for discovery and therapeutic purposes. As a general principle, they build new technologies to intervene in human disease using molecular parts sourced from bacteria. For instance, Shipman’s team developed a way to record the order in which genes turn on in a living cell by co-opting two different bacterial immune systems, the retron system and the CRISPR system. His team plans to use that technology to understand how the order of gene expression during development drives the formation of different cells types and tissues. They are also working to improve the precision of genome editing technologies that will be used to correct disease-causing mutations, by using bacterial retroelements alongside CRISPR-Cas9.
Areas of Expertise
The philosophy driving Shipman’s research is to identify a technical limitation in a given field and tackle it with innovative approaches borrowing from diverse fields, such as bioengineering, genetics, systems and synthetic biology, neuroscience, microbiology, and chemical biology. With this mindset, Shipman addresses the fundamental question of the relative timing of gene expression with a technology that logs a record of sequential events in the DNA of living cells. The lab also harnesses molecular components from bacterial immune systems to make precise modifications to the human genome.
Associate Investigator, Gladstone Institutes
Assistant Professor, Department of Bioengineering and Therapeutic Sciences, UC San Francisco
Seth Shipman is an associate investigator at Gladstone Institutes. He is also an assistant professor in the Department of Bioengineering and Therapeutic Sciences at UC San Francisco, as well as a CZ Biohub Investigator.
Shipman holds a BA in Neuroscience from Wesleyan University and a PhD in Neuroscience from UC San Francisco, where he worked with Roger Nicoll to understand the molecular events that drive formation of synapses in the brain. His graduate work uncovered how a family of adhesion molecules called neuroligins can influence both synaptogenesis and plasticity. He conducted postdoctoral research in genetics, synthetic biology and stem cell biology at Harvard Medical School and Harvard University with George Church and Jeffrey Macklis, where he developed an approach to store information into the genomic DNA of living cells. This work was featured in The New York Times, The Atlantic, and elsewhere and was named as one of Discover Magazine’s top 25 stories of the year.
“I came to Gladstone to tackle the biggest questions about human disease, but with the freedom to use innovative approaches and follow the science wherever it takes me.”
Honors and Awards
2022 CZ Biohub Investigator
2020 NIH New Innovator
2020 Pew Biomedical Scholar
2019 ScienceNews: The SN 10, Scientists to Watch
2019 SFARI Bridge to Independence Award
2018 DARPA Riser, DARPA 60th Anniversary Symposium
2014 Life Science Research Foundation Postdoctoral Award
2011 Grass Fellowship in Neuroscience (declined), Grass Foundation
- Recording gene expression order in DNA by CRISPR addition of retron barcodes. Bhattarai-Kline S, Lear SK, Fishman CB, Lopez SC, Lockshin ER, Schubert MG, Nivala J, Church GM, Shipman SL. Nature. 2022 08; 608(7921):217-225.
- Retron reverse transcriptase termination and phage defense are dependent on host RNase H1. Palka C, Fishman CB, Bhattarai-Kline S, Myers SA, Shipman SL. Nucleic Acids Res. 2022 04 08; 50(6):3490-3504.
- Precise genome editing across kingdoms of life using retron-derived DNA. Lopez SC, Crawford KD, Lear SK, Bhattarai-Kline S, Shipman SL. Nat Chem Biol. 2022 02; 18(2):199-206.
- High-throughput functional variant screens via in vivo production of single-stranded DNA. Schubert MG, Goodman DB, Wannier TM, Kaur D, Farzadfard F, Lu TK, Shipman SL, Church GM. Proc Natl Acad Sci U S A. 2021 05 04; 118(18).
- One-step data storage in cellular DNA. Bhattarai-Kline S, Lear SK, Shipman SL. Nat Chem Biol. 2021 03; 17(3):232-233.
- Characterizing the portability of phage-encoded homologous recombination proteins. Filsinger GT, Wannier TM, Pedersen FB, Lutz ID, Zhang J, Stork DA, Debnath A, Gozzi K, Kuchwara H, Volf V, Wang S, Rios X, Gregg CJ, Lajoie MJ, Shipman SL, Aach J, Laub MT, Church GM. Nat Chem Biol. 2021 04; 17(4):394-402.
- A comprehensive library of human transcription factors for cell fate engineering. Ng AHM, Khoshakhlagh P, Rojo Arias JE, Pasquini G, Wang K, Swiersy A, Shipman SL, Appleton E, Kiaee K, Kohman RE, Vernet A, Dysart M, Leeper K, Saylor W, Huang JY, Graveline A, Taipale J, Hill DE, Vidal M, Melero-Martin JM, Busskamp V, Church GM. Nat Biotechnol. 2021 04; 39(4):510-519.
- Spontaneous CRISPR loci generation in vivo by non-canonical spacer integration. Nivala J, Shipman SL, Church GM. Nat Microbiol. 2018 03; 3(3):310-318.
- CRISPR-Cas encoding of a digital movie into the genomes of a population of living bacteria. Shipman SL, Nivala J, Macklis JD, Church GM. Nature. 2017 07 20; 547(7663):345-349.
- Molecular recordings by directed CRISPR spacer acquisition. Shipman SL, Nivala J, Macklis JD, Church GM. Science. 2016 Jul 29; 353(6298):aaf1175.
- The cellular and molecular landscape of neuroligins. Bemben MA, Shipman SL, Nicoll RA, Roche KW. Trends Neurosci. 2015 Aug; 38(8):496-505.
- Rapid neurogenesis through transcriptional activation in human stem cells. Busskamp V, Lewis NE, Guye P, Ng AH, Shipman SL, Byrne SM, Sanjana NE, Murn J, Li Y, Li S, Stadler M, Weiss R, Church GM. Mol Syst Biol. 2014 Nov 17; 10:760.
- CaMKII phosphorylation of neuroligin-1 regulates excitatory synapses. Bemben MA, Shipman SL, Hirai T, Herring BE, Li Y, Badger JD, Nicoll RA, Diamond JS, Roche KW. Nat Neurosci. 2014 Jan; 17(1):56-64.
- Distance-dependent scaling of AMPARs is cell-autonomous and GluA2 dependent. Shipman SL, Herring BE, Suh YH, Roche KW, Nicoll RA. J Neurosci. 2013 Aug 14; 33(33):13312-9.
- Dimerization of postsynaptic neuroligin drives synaptic assembly via transsynaptic clustering of neurexin. Shipman SL, Nicoll RA. Proc Natl Acad Sci U S A. 2012 Nov 20; 109(47):19432-7.
- A subtype-specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Shipman SL, Nicoll RA. Neuron. 2012 Oct 18; 76(2):309-16.
- Functional dependence of neuroligin on a new non-PDZ intracellular domain. Shipman SL, Schnell E, Hirai T, Chen BS, Roche KW, Nicoll RA. Nat Neurosci. 2011 Jun; 14(6):718-26.
- Absence of established sex differences in patients with schizophrenia on a two-dimensional object array task. Shipman SL, Baker EK, Pearlson G, Astur RS. Psychiatry Res. 2009 Apr 30; 166(2-3):158-65.
- Factors affecting the hippocampal BOLD response during spatial memory. Shipman SL, Astur RS. Behav Brain Res. 2008 Mar 05; 187(2):433-41.