Functional Genomics Platform

The Functional Genomics Platform at Whitehead Institute works collaboratively with researchers to develop and apply CRISPR-Cas9-based and other large-scale screening approaches to answer diverse biological questions, with a particular interest and expertise in improving the delivery of CRISPR-Cas9 machinery to enable large-scale screens in challenging model systems and in vivo.
The FGP is directed by Heather Keys, Ph.D.
Jonathan Weissman, Ph.D. is the faculty advisor for the FGP.
On this website, you can find more details about our work, our team, contact information, and protocols.
Our Work
We work collaboratively with researchers and provide expertise for all stages of the screening process:
- Experimental design
- Technology development
- sgRNA library design, cloning, and propagation
- Virus preparation for optimization and screening
- Vector design
- Sequencing library preparation
- Data analysis
- Follow-up strategies
Team
Heather Keys, Ph.D.
Director
Ninna Velasco, B.A.
Technical Assistant I
Charlotte Gordon
MIT Undergraduate
Interested in joining the team?
Contact us!
Alumni
Stephanie Esonwune, Arbor Biotechnologies
Olena Fedoniuk, Lonza
Austin Garner, Oxford Nanopore Technologies
Sandra Kalil Perdomo
Mehreen Khan, Alnylam Pharmaceuticals
Adina Kirkland
Rachel Simoes, Arizona State University
Maria Virgilio, University of Michigan PhD Program
Keya Viswanathan, Trinity Life Sciences
Former Masters Students
Nicole Eischer, Max Planck Institute for Molecular Genetics PhD Program
Manuel Mastel, DKFZ Helmholz International Graduate School for Cancer Research PhD Program
Former High School Interns
Blen Gebremichael
Join Us
We are always on the lookout for enthusiastic, curious, and kind individuals who are excited to challenge themselves to learn new skills and think deeply about their projects in a fast-paced environment. Whether you are looking for a long-term career path focused on collaborative, cutting-edge science, short-term training in molecular biological and mammalian cell culture techniques, or are a Masters student considering a CRISPR screening or technology development project, please contact us!
Materials
Here we will post basic protocols for screening and related experiments. More coming soon!
Any questions? Contact us.
Protocols
- Small-scale Lentiviral Preparation
- Large-scale Lentiviral Preparation
- Titer Test
- Propagation of Pooled Plasmid Libraries
- Coming Soon!: Transduction Test for New Cell Lines
- Coming Soon!: Genomic DNA Miniprep
- Coming Soon!: Genomic DNA Maxiprep
- Coming Soon!: Sequencing Library Preparation
- Coming Soon!: Bead Cleanup and dsDNA Quantification
- Coming Soon!: Transduction Conditions for Cancer Cell Lines
- Coming Soon!: Materials Reference List
Publications
- Genetically encoded fluorescent reporter for polyamines. Sharma P, Kim CY, Keys HR, Imada S, Joseph AB, Ferro L, Kunchok T, Anderson R, Yilmaz O, Weng JK, Jain A. bioRxiv [Preprint]. 2024 Nov 17:2024.08.24.609500. doi: 10.1101/2024.08.24.609500. PMID: 39253442
- SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. Pena IA, Shi JS, Chang SM, Yang J, Block S, Adelmann CH, Keys HR, Ge P, Bathla S, Witham IH, Sienski G, Nairn AC, Sabatini DM, Lewis CA, Kory N, Vander Heiden MG, Heiman M. Nat Commun. 2025 Jan 24;16(1):978. doi: 10.1038/s41467-025-56130-3. PMID: 39856062
- Functional genetics reveals modulators of antimicrotubule drug sensitivity. Su KC, Radul E, Maier NK, Tsang MJ, Goul C, Moodie B, Marescal O, Keys HR, Cheeseman IM. J Cell Biol. 2025 Feb 3;224(2):e202403065. doi: 10.1083/jcb.202403065. Epub 2024 Nov 21. PMID: 39570287
- Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death. Lam B, Kajderowicz KM, Keys HR, Roessler JM, Frenkel EM, Kirkland A, Bisht P, El-Brolosy MA, Jaenisch R, Bell GW, Weissman JS, Griffith EC, Hrvatin S. bioRxiv [Preprint]. 2024 Nov 19:2024.07.25.605098. doi: 10.1101/2024.07.25.605098. PMID: 39091747
- Coupled protein quality control during nonsense-mediated mRNA decay. Inglis, A.J., Guna, A., Galvez-Merchan, A., Pal, A., Esantsi, T.K., Keys, H.R., Frenkel, E.M., Oania, R., Weissman, J.S., Voorhees, R.M. J Cell Sci 2023 May 15;136(10). doi: 10.1242/jcs.261216. PMCID: PMC10234110.
- Genome-scale CRISPR screening in a single mouse liver. Keys, H.R.* & Knouse, K. A.* Cell Genomics 2022 Dec 14;2(12). doi: 10.1016/j.xgen.2022.100217. PMCID: PMC9835819. *equal contribution
- Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction. JM, Fresenius HL, Cunningham CN, Wei P, Keys HR, Berg J, Bott A, Yadav T, Ryan J, Sirohi D, Tripp SR, Barta P, Agarwal N, Letai A, Sabatini DM, Wohlever ML, Rutter J. Elife 2022 Nov 21;11:e82860. doi: 10.7554/eLife.82860. PMID: 36409067.
- Genome-wide CRISPR screen identifies PRC2 and KMT2D-COMPASS as regulators of distinct EMT trajectories that contribute differentially to metastasis. Zhang Y, Donaher JL, Das S, Li X, Reinhardt F, Krall JA, Lambert AW, Thiru P, Keys HR, Khan M, Hofree M, Wilson MM, Yedier-Bayram O, Lack NA, Onder TT, Bagci-Onder T, Tyler M, Tirosh I, Regev A, Lees J, Weinberg RA. Nat Cell Biol 24, 554–564 (2022). doi: 10.1038/s41556-022-00877-0. Epub 2022 Apr 11. PubMed PMID: 35411083.
- CRISPR screens in physiologic medium reveal conditionally essential genes in human cells. Rossiter NJ, Huggler KS, Adelmann CH, Keys HR, Soens RW, Sabatini DM, Cantor JR. Cell Metab. 2021 Jun 1;33(6):1248-1263.e9. doi: 10.1016/j.cmet.2021.02.005. Epub 2021 Mar 1. PubMed PMID: 33651980. PubMed Central PMCID: PMC8172426.
- Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Zou Y*, Henry WS*, Ricq EL, Graham ET, Phadnis VV, Maretich P, Paradkar S, Boehnke N, Deik AA, Reinhardt F, Eaton JK, Ferguson B, Wang W, Fairman J, Keys HR, Dančík V, Clish CB, Clemons PA, Hammond PT, Boyer LA, Weinberg RA, Schreiber SL. Nature. 2020 Sep;585(7826):603-608. doi: 10.1038/s41586-020-2732-8. Epub 2020 Sep 16. PubMed PMID: 32939090; PubMed Central PMCID: PMC8051864. *equal contribution
- Mitochondrial metabolism promotes adaptation to proteotoxic stress. Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, Thiru P, Reidy M, Kugener G, Rossen J, Kocak M, Kory N, Tsherniak A, Santagata S, Whitesell L, Ghobrial IM, Markley JL, Lindquist S, Golub T. Nature Chemical Biology. 2019 Jul; 15(7):681-689. doi: 10.1038/s41589-019-0291-9
- Genome-wide CRISPR screen for Zika virus resistance in human neural cells. *Li Y, *Muffat J, *Javed AO, *Keys HR, Lungjangwa T, Bosch I, Khan M, Virgilio MC, Gehrke L, Sabatini DM, Jaenisch R. PNAS . 2019 Apr 24. doi: 10.1073/pnas.1900867116
*equal contribution - SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. Kory N, Wyant GA, Prakash G, Uit de Bos J, Bottanelli F, Pacold ME, Chan SH, Lweis CA, Wang T, Keys HR, Guo YE, Sabatini DM. Science 362(6416). 2018 Nov 16. doi: 10.1126/science.aat9528
- Histidine catabolism is a major determinant of methotrexate sensitivity. Kanarek N, Keys HR, Cantor JR, Lewis CA, Chan SH, Kunchok T, Abu-Remaileh M, Freinkman E, Schweitzer LD, Sabatini DM. Nature 559:632-636. 2018 July 11. doi: 10.1038/s41586-018-0316-7
Contact Us
We are located at the Whitehead Institute, 455 Main Street, Cambridge, MA.
Please contact Heather Keys, Ph.D. by email with all questions.