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Meru J. Sadhu, Ph.D.

Stadtman Investigator

Systems Biology and Genome Engineering Section

Head

Systems Biology and Genome Engineering Section

Education

B.S. California Institute of Technology

Ph.D. University of California at Berkeley

Contact Info
BG 49 RM 4A82
49 CONVENT DR
BETHESDA MD 20892

Scientific Summary

The Systems Biology and Genome Engineering Section's goal is to systematically understand the phenotypic consequences of genetic differences. By studying the functional effects of genetic heterogeneity, such as natural variation between individuals or between species, or novel genetic changes that we create, section researchers work to understand the principles linking genetic and phenotypic variation. As the space of potential genetic variants is immense, the section devises strategies to study large numbers of genetic differences in parallel. These strategies leverage the strengths of CRISPR technologies, large-scale oligonucleotide synthesis, the power of the yeast model system, and high-throughput phenotyping and genotyping to generate and study the effects of thousands of unique genetic variants. In addition to applying existing genome engineering methods, the section aims to further expand the reach of genomics by developing new and powerful approaches to study genetic heterogeneity.

Selected Publications

Iturralde AB, Weller CA, Sadhu MJ. Comprehensive deletion scan of anti-CRISPR AcrIIA4 reveals essential and dispensable domains for Cas9 inhibition. bioRxiv [Preprint]. 2024 Jul 9:2024.07.09.602757. doi: 10.1101/2024.07.09.602757. Update in: Proc Natl Acad Sci U S A. 2024 Nov 26;121(48):e2413743121. doi: 10.1073/pnas.2413743121. 

Chambers MJ, Scobell SB, Sadhu MJ. Systematic genetic characterization of the human PKR kinase domain highlights its functional malleability to escape a poxvirus substrate mimic. Elife. 2024 Nov 12;13:RP99575. doi: 10.7554/eLife.99575. 

Weller CA, Andreev I, Chambers MJ, Park M; NISC Comparative Sequencing Program; Bloom JS, Sadhu MJ. Highly complete long-read genomes reveal pangenomic variation underlying yeast phenotypic diversity. Genome Research. 33(5):729-740. 2023.

Andreev I, Laidlaw KME, Giovanetti SM, Urtecho G, Shriner D, Bloom JS, MacDonald C, Sadhu MJ. Discovery of a rapidly evolving yeast defense factor, KTD1, against the secreted killer toxin K28. PNAS. 120(8):e2217194120. 2023.

Schubert OT, Bloom JS, Sadhu MJ, Kruglyak L. Genome-wide base editor screen identifies regulators of protein abundance in yeast. eLife. 2022 Nov 3;11:e79525. doi: 10.7554/eLife.79525. 2022.

Boocock J, Sadhu MJ, Durvasula A, Bloom JS, Kruglyak L. Ancient balancing selection maintains incompatible versions of the galactose pathway in yeast. Science. 22;371(6527):415-419. 2021.

Bloom JS, Boocock J, Treusch S, Sadhu MJ, Day L, Oates-Barker H, Kruglyak L. Rare variants contribute disproportionately to quantitative trait variation in yeast. eLife. 24;8:e49212. doi: 10.7554/eLife.49212. 2019.

Sadhu MJ, Bloom JS, Day L, Siegel JJ, Kosuri S, Kruglyak L. Highly parallel genome variant engineering with CRISPR-Cas9. Nat Genet. 50(4):510-514. 2018.

Forsberg SK, Bloom JS, Sadhu MJ, Kruglyak L, Carlborg Ö. Accounting for genetic interactions improves modeling of individual quantitative trait phenotypes in yeast. Nat Genet. 49(4):497-503. 2017.

Sadhu MJ, Bloom JS, Day L, Kruglyak L. CRISPR-directed mitotic recombination enables genetic mapping without crosses. Science. 352(6289):1113-6. 2016.

View full publications list

Systems Biology and Genome Engineering Section Staff

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Simone Giovanetti
  • Lab Manager
  • Systems Biology and Genome Engineering Section
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Michael Chambers, Ph.D.
  • Postdoctoral Fellow
  • Systems Biology and Genome Engineering Section
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Mudabir Abdullah, Ph.D.
  • Postdoctoral Fellow
  • Systems Biology and Genome Engineering Section
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Fereshteh Azadeh, Ph.D.
  • Postdoctoral Fellow
  • Systems Biology and Genome Engineering Section
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Dinie Zheng
  • Postbaccalaureate Fellow
  • Systems Biology and Genome Engineering Section
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Tristan Grieve
  • Postbaccalaureate Fellow
  • Systems Biology and Genome Engineering Section
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Emily Knisely-Durham
  • Postbaccalaureate Fellow
  • Systems Biology and Genome Engineering Section

Alumni

  • Sophie Scobell; Postbac (2022-2024); National Taiwan University - M.S. Student

  • Annette Iturralde; Postbac (2022-2024); University of Virginia - Ph. D. Student

  • Cory Weller; Postdoc (2019-2022); NIH Center for Alzheimer’s and Related Dementias – Research Scientist

  • Apoorva Ravishankar; Postdoc (2020-2022); Amazon – Research Scientist

  • Molly Monge; Postbac (2021-2023); Weill Cornell, Rockefeller, MSKCC – M.D. Ph.D. Student

  • Ilya Andreev; Postbac (2019-2021); MIT Biology – Ph.D. Student

Biography

Meru Sadhu is an Earl Stadtman Investigator and head of the Systems Biology and Genome Engineering section at the National Human Genome Research Institute. He obtained his Bachelor's degree from Caltech, and then did his doctoral studies at UC Berkeley with Jasper Rine. For his postdoc, Dr. Sadhu joined Leonid Kruglyak's lab at UCLA, to complement his background in classical genetics with training in quantitative genetics. He developed approaches to apply CRISPR technology to quantitative genetics questions, including using CRISPR to direct recombination, and also to examine in parallel the effects of thousands of specific genetic variants. In 2018 he came to the NIH and formed the Systems Biology and Genome Engineering Section, where he is using high-throughput methods to address important questions in genetics.

 

2019 Symposium

 

Job Openings

Postdoctoral Position in Systems Biology and Genome Engineering | NHGRI
Jobs at NHGRI
Postdoctoral Position in Systems Biology and Genome Engineering

Last updated: February 12, 2025