Britt Adamson
Assistant Professor, Molecular Biology and Lewis-Sigler Institute for Integrative Genomics

Areas of Research: Cell Biology, Genetics, Functional Genomics, Technology Development
Department|Program:
  • Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics

badamson@princeton.edu
609-258-3109
144 Carl Icahn Lab

Faculty Assistant:
Dawn Capizzi
dcapizzi@princeton.edu
609-258-1617
Scholar

RESEARCH FOCUS:
The organization of cellular stress response networks and repair mechanisms

The Adamson lab studies the organization and function of molecular networks in human cells, with particular focus on understanding (a) how cells differentially leverage these networks to respond to stress and (b) how abnormal programs of stress response contribute to disease. We also develop and improve innovative technologies for genetics and cell biology, including those with potential therapeutic applications such as genome editing.

Stress response networks have traditionally been studied in bulk assays and thus have been described largely as dedicated pathways with stereotyped activation regimes. However, we know that these systems are deeply complex, with diverse sensory mechanisms and integrated subroutines controlling cell outcomes. This complexity helps maintain normal cell function in response to diverse perturbations. Problematically, it can also allow cells to survive pathogenic network dysregulation or enable abnormal adaptation to multicellular disease states. Therefore, understanding stress responses at a systems-level and from a functional perspective is critical. We use and develop innovative experimental technologies, including CRISPR-based functional genomics, single-cell RNA-sequencing, and genetic interaction mapping, to investigate molecular and genetic networks. These high-resolution techniques allow systematic mapping of network behavior across conditions. From this, we identify interesting behaviors, with special interest in context-dependent behaviors, and then, using more conventional genetics and cell biology approaches, characterize underlying mechanisms. Current efforts include investigating how cells mount tailored responses to endoplasmic reticulum stress and DNA damage.

Genome editing technologies that target programmable sequence changes to specific genomic loci have substantial potential for therapeutic applications. However, realizing the promise of these approaches will require improving their to-date limited specificity. We have recently pioneered methods to systematically investigate how synthetic mechanisms of genome editing, including CRISPR-based single-strand template repair and DNA base editing, interact with endogenous DNA repair networks. One goal of this work is to identify parameters that can be tuned to achieve optimal in vitro and in vivo editing outcomes.

SELECT PUBLICATIONS

Chan M, Smith ZD, Grosswendt S, Kretzmer H, Norman T, Adamson B, Jost M, Quinn JJ, Yang D, A Meissner, & Weissman JS. Molecular recording of mammalian embryogenesis. bioRxiv https://doi.org/10.1101/384925 (2018).

Horlbeck MA, Xu A, Wang M, Bennett NK, Park CY, Bogdanoff D, Adamson B, Chow ED, Kampmann M, Peterson TR, Nakamura K, Fischbach MA, Weissman JS, & Gilbert LA. Mapping the genetic landscape of human cells. Cell 174, 953-967 (2018).

Adamson B, Norman TM, Jost M, & Weissman JS. Approaches to maximize sgRNA-barcode coupling in Perturb-seq screens. bioRxiv https://doi.org/10.1101/298349 (2018).

Adamson B, Norman TM, Jost M, Cho MY, Nuñez JK, Chen Y, Villalta JE, Gilbert LA, Horlbeck MA, Hein MY, Pak RA, Gray AN, Gross CA, Dixit A, Parnas O, Regev A, & Weissman JS. A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Cell 167, 1867-1822 (2016).

Dixit A, Parnas O, Li B, Chen J, Fulco CP, Jerby-Arnon L, Marjanovic ND, Dionne D, Burks T, Raychowdhury R, Adamson B, Norman TM, Lander ES, Weissman JS, Friedman N, & Regev A. Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. Cell 167, 1853-1866 (2016).

Horlbeck MA, Gilbert LA, Villalta JE, Adamson B, Pak RA, Chen Y, Fields AP, Park CY, Corn JE, Kampmann M, & Weissman JS. Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. eLife 5 (2016).

Izhar L, Adamson B, Ciccia A, Lewis J, Pontano-Vaites L, Leng Y, Liang AC, Westbrook T, Harper JW, & Elledge SJ. A systematic analysis of factors localized to damaged chromatin reveals PARP-dependent recruitment of transcription factors. Cell Rep 11, 1486-1500 (2015).

Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, Qi LS, Kampmann M, & Weissman JS. Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation. Cell 159, 647-661 (2014).

Ciccia A, Nimonkar AV, Hu Y, Hajdu I, Achar YJ, Izhar L, Petit SA, Adamson B, Yoon JC, Kowalczykowski SC, Livingston DM, Haracska L, & Elledge SJ. Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress. Mol Cell 47, 396-409 (2012).

Adamson B, Smogorzewska A, Sigoillot FD, King RW, & Elledge SJ. A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response. Nat Cell Biol 14, 318-328 (2012).

Sigoillot FD, Lyman S, Huckins JF, Adamson B, Chung E, Quattrochi B, & King RW. A bioinformatics method identifies prominent off-targeted transcripts in RNAi screens. Nat Methods 9, 363-366 (2012).

O’Connell BC, Adamson B, Lydeard JR, Sowa ME, Ciccia A, Bredemeyer AL, Schlabach M, Gygi SP, Elledge SJ, & Harper JW. A Genome-wide Camptothecin Sensitivity Screen Identifies a Mammalian MMS22L-NFKBIL2 Complex Required for Genomic Stability. Mol Cell 40, 645-657 (2010).

Chou DM, Adamson B, Dephoure NE, Tan X, Nottke AC, Hurov KE, Gygi SP, Colaiácovo MP, & Elledge SJ. A chromatin localization screen reveals poly(ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage. Proc Natl Acad Sci USA 107, 18475-18480 (2010).