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Richard Irving Sherwood, Ph.D.


Available: 10/16/20, Expires: 08/01/23

Our lab develops high-throughput CRISPR-Cas9 screening technologies to investigate the genetic basis of disease. We have several opportunities available in improving these technologies and applying them to study genetic disease. In one such project, we are dissecting mechanisms by which common variation (identified in GWAS) contributes to cholesterol levels using scalable CRISPR screening approaches.

Available: 01/10/22, Expires: 03/01/24

Our lab (http://sherwoodlab.bwh.harvard.edu/) is a highly interdisciplinary and collaborative environment that combines CRISPR-Cas9 genome editing and genomic screening approaches with cutting edge machine learning and computational genetics approaches to understand how genomic variants contribute to complex human disease and to develop genetic treatments. We have developed a number of innovative, unpublished screening platforms to understand lipid and cholesterol metabolism, which we are applying to better understand and diminish cardiovascular risk. Wet-lab and computational projects are available for students.

Available: 12/06/22, Expires: 12/31/24

The Sherwood Lab in the Division of Genetics at Brigham and Women’s Hospital and Harvard Medical School is a highly interdisciplinary and collaborative environment that combines CRISPR-Cas9 genome editing and genomic screening approaches with cutting edge machine learning and computational genetics approaches to understand how genomic variants contribute to complex human disease and to develop genetic treatments. In particular, we have developed several novel high-throughput CRISPR screening assays to study lipid homeostasis, and we are combining these scalable genetic screening platforms with analysis of UK Biobank quantitative serum lipid data to deepen understanding of genetic contribution to lipid levels. An experimentally-focused student would apply cutting-edge CRISPR techniques such as base and prime editing toward these questions, and a computational student would analyze UK Biobank cohort data in concert with our cellular screening results.

The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. UM1HG012010 (PINELLO, LUCA) Sep 1, 2021 - May 31, 2026
    Comprehensive characterization of variants underlying heart and blood diseases with CRISPR base editing
    Role: Co-Principal Investigator
  2. R21HG010391 (SHERWOOD, RICHARD I) Feb 11, 2019 - Jan 31, 2021
    Correcting genetic disorders using predictable CRISPR/Cas9-induced exon skipping
    Role: Principal Investigator
  3. R21OD025309 (SHERWOOD, RICHARD I) Jan 15, 2019 - Dec 31, 2021
    Systematic unlocking of airway stem cell differentiation program
    Role: Principal Investigator
  4. K01DK101684 (SHERWOOD, RICHARD I) May 1, 2014 - Feb 28, 2019
    Predictive transcription factor modeling to program endodermal cell fates
    Role: Principal Investigator

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Velimirovic M, Zanetti LC, Shen MW, Fife JD, Lin L, Cha M, Akinci E, Barnum D, Yu T, Sherwood RI. Peptide fusion improves prime editing efficiency. Nat Commun. 2022 06 18; 13(1):3512. PMID: 35717416; PMCID: PMC9206660.
    Citations: 1     Fields:    Translation:Cells
  2. Bermudez-Cabrera HC, Culbertson S, Barkal S, Holmes B, Shen MW, Zhang S, Gifford DK, Sherwood RI. Small molecule inhibition of ATM kinase increases CRISPR-Cas9 1-bp insertion frequency. Nat Commun. 2021 08 25; 12(1):5111. PMID: 34433825.
    Citations: 2     Fields:    Translation:HumansAnimalsCells
  3. Akinci E, Hamilton MC, Khowpinitchai B, Sherwood RI. Using CRISPR to understand and manipulate gene regulation. Development. 2021 05 01; 148(9). PMID: 33913466; PMCID: PMC8126405.
    Citations:    Fields:    Translation:HumansAnimalsCells
  4. Yeo GHT, Juez O, Chen Q, Banerjee B, Chu L, Shen MW, Sabry M, Logister I, Sherwood RI, Gifford DK. Detection of gene cis-regulatory element perturbations in single-cell transcriptomes. PLoS Comput Biol. 2021 03; 17(3):e1008789. PMID: 33711017; PMCID: PMC8011753.
    Citations:    Fields:    Translation:HumansAnimalsCells
  5. Louie W, Shen MW, Tahiry Z, Zhang S, Worstell D, Cassa CA, Sherwood RI, Gifford DK. Machine learning based CRISPR gRNA design for therapeutic exon skipping. PLoS Comput Biol. 2021 01; 17(1):e1008605. PMID: 33417623; PMCID: PMC7819613.
    Citations:    Fields:    Translation:HumansAnimalsCells
  6. Lin L, Holmes B, Shen MW, Kammeron D, Geijsen N, Gifford DK, Sherwood RI. Comprehensive Mapping of Key Regulatory Networks that Drive Oncogene Expression. Cell Rep. 2020 11 24; 33(8):108426. PMID: 33238122; PMCID: PMC7724632.
    Citations: 4     Fields:    Translation:HumansCells
  7. Sreekanth V, Zhou Q, Kokkonda P, Bermudez-Cabrera HC, Lim D, Law BK, Holmes BR, Chaudhary SK, Pergu R, Leger BS, Walker JA, Gifford DK, Sherwood RI, Choudhary A. Chemogenetic System Demonstrates That Cas9 Longevity Impacts Genome Editing Outcomes. ACS Cent Sci. 2020 Dec 23; 6(12):2228-2237. PMID: 33376784.
    Citations: 3     
  8. Hammelman J, Krismer K, Banerjee B, Gifford DK, Sherwood RI. Identification of determinants of differential chromatin accessibility through a massively parallel genome-integrated reporter assay. Genome Res. 2020 10; 30(10):1468-1480. PMID: 32973041.
    Citations: 6     Fields:    Translation:AnimalsCells
  9. Szczesnik T, Chu L, Ho JWK, Sherwood RI. A High-Throughput Genome-Integrated Assay Reveals Spatial Dependencies Governing Tcf7l2 Binding. Cell Syst. 2020 09 23; 11(3):315-327.e5. PMID: 32910904; PMCID: PMC7530048.
    Citations: 1     Fields:    Translation:HumansCells
  10. Akinci E, Cha M, Lin L, Yeo G, Hamilton MC, Donahue CJ, Bermudez-Cabrera HC, Zanetti LC, Chen M, Barkal SA, Khowpinitchai B, Chu N, Velimirovic M, Jodhani R, Fife JD, Sovrovic M, Cole PA, Davey RA, Cassa CA, Sherwood RI. Elucidation of remdesivir cytotoxicity pathways through genome-wide CRISPR-Cas9 screening and transcriptomics. bioRxiv. 2020 Aug 28. PMID: 32869031; PMCID: PMC7457617.
  11. Yeo GHT, Lin L, Qi CY, Cha M, Gifford DK, Sherwood RI. A Multiplexed Barcodelet Single-Cell RNA-Seq Approach Elucidates Combinatorial Signaling Pathways that Drive ESC Differentiation. Cell Stem Cell. 2020 06 04; 26(6):938-950.e6. PMID: 32459995.
    Citations: 3     Fields:    Translation:Cells
  12. Szczesnik T, Ho JWK, Sherwood R. Dam mutants provide improved sensitivity and spatial resolution for profiling transcription factor binding. Epigenetics Chromatin. 2019 06 13; 12(1):36. PMID: 31196130; PMCID: PMC6567924.
    Citations: 5     Fields:    Translation:AnimalsCells
  13. Shen MW, Arbab M, Hsu JY, Worstell D, Culbertson SJ, Krabbe O, Cassa CA, Liu DR, Gifford DK, Sherwood RI. Author Correction: Predictable and precise template-free CRISPR editing of pathogenic variants. Nature. 2019 03; 567(7746):E1-E2. PMID: 30765887.
    Citations: 3     Fields:    
  14. Shen MW, Arbab M, Hsu JY, Worstell D, Culbertson SJ, Krabbe O, Cassa CA, Liu DR, Gifford DK, Sherwood RI. Predictable and precise template-free CRISPR editing of pathogenic variants. Nature. 2018 11; 563(7733):646-651. PMID: 30405244.
    Citations: 174     Fields:    Translation:HumansCells
  15. Kang D, Sherwood R, Barkal A, Hashimoto T, Engstrom L, Gifford D. DNase-capture reveals differential transcription factor binding modalities. PLoS One. 2017; 12(12):e0187046. PMID: 29284001.
    Citations:    Fields:    Translation:Cells
  16. Betancur PA, Abraham BJ, Yiu YY, Willingham SB, Khameneh F, Zarnegar M, Kuo AH, McKenna K, Kojima Y, Leeper NJ, Ho P, Gip P, Swigut T, Sherwood RI, Clarke MF, Somlo G, Young RA, Weissman IL. A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer. Nat Commun. 2017 04 05; 8:14802. PMID: 28378740; PMCID: PMC5382276.
    Citations: 80     Fields:    Translation:HumansAnimalsCells
  17. Banerjee B, Sherwood RI. A CRISPR view of gene regulation. Curr Opin Syst Biol. 2017 Feb; 1:1-8. PMID: 28966990; PMCID: PMC5619677.
    Citations: 5     
  18. Arbab M, Sherwood RI. Self-Cloning CRISPR. Curr Protoc Stem Cell Biol. 2016 08 17; 38:5B.5.1-5B.5.16. PMID: 27532819.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  19. Hashimoto T, Sherwood RI, Kang DD, Rajagopal N, Barkal AA, Zeng H, Emons BJ, Srinivasan S, Jaakkola T, Gifford DK. A synergistic DNA logic predicts genome-wide chromatin accessibility. Genome Res. 2016 10; 26(10):1430-1440. PMID: 27456004; PMCID: PMC5052050.
    Citations: 11     Fields:    Translation:HumansAnimalsCells
  20. Ferreira LM, Meissner TB, Mikkelsen TS, Mallard W, O'Donnell CW, Tilburgs T, Gomes HA, Camahort R, Sherwood RI, Gifford DK, Rinn JL, Cowan CA, Strominger JL. A distant trophoblast-specific enhancer controls HLA-G expression at the maternal-fetal interface. Proc Natl Acad Sci U S A. 2016 May 10; 113(19):5364-9. PMID: 27078102; PMCID: PMC4868469.
    Citations: 39     Fields:    Translation:HumansCells
  21. Barkal AA, Srinivasan S, Hashimoto T, Gifford DK, Sherwood RI. Cas9 Functionally Opens Chromatin. PLoS One. 2016; 11(3):e0152683. PMID: 27031353.
    Citations: 12     Fields:    Translation:AnimalsCells
  22. Rajagopal N, Srinivasan S, Kooshesh K, Guo Y, Edwards MD, Banerjee B, Syed T, Emons BJ, Gifford DK, Sherwood RI. High-throughput mapping of regulatory DNA. Nat Biotechnol. 2016 Feb; 34(2):167-74. PMID: 26807528; PMCID: PMC5108523.
    Citations: 111     Fields:    Translation:Animals
  23. Arbab M, Srinivasan S, Hashimoto T, Geijsen N, Sherwood RI. Cloning-free CRISPR. Stem Cell Reports. 2015 Nov 10; 5(5):908-917. PMID: 26527385.
    Citations: 19     Fields:    Translation:HumansAnimalsCells
  24. Wamaitha SE, del Valle I, Cho LT, Wei Y, Fogarty NM, Blakeley P, Sherwood RI, Ji H, Niakan KK. Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells. Genes Dev. 2015 Jun 15; 29(12):1239-55. PMID: 26109048; PMCID: PMC4495396.
    Citations: 42     Fields:    Translation:HumansAnimalsCells
  25. Mahony S, Edwards MD, Mazzoni EO, Sherwood RI, Kakumanu A, Morrison CA, Wichterle H, Gifford DK. An integrated model of multiple-condition ChIP-Seq data reveals predeterminants of Cdx2 binding. PLoS Comput Biol. 2014 Mar; 10(3):e1003501. PMID: 24675637.
    Citations: 40     Fields:    Translation:AnimalsCells
  26. Nissim S, Sherwood RI, Wucherpfennig J, Saunders D, Harris JM, Esain V, Carroll KJ, Frechette GM, Kim AJ, Hwang KL, Cutting CC, Elledge S, North TE, Goessling W. Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Dev Cell. 2014 Feb 24; 28(4):423-37. PMID: 24530296.
    Citations: 21     Fields:    Translation:AnimalsCells
  27. Sherwood RI, Hashimoto T, O'Donnell CW, Lewis S, Barkal AA, van Hoff JP, Karun V, Jaakkola T, Gifford DK. Discovery of directional and nondirectional pioneer transcription factors by modeling DNase profile magnitude and shape. Nat Biotechnol. 2014 Feb; 32(2):171-178. PMID: 24441470.
    Citations: 225     Fields:    Translation:Cells
  28. Chen AE, Borowiak M, Sherwood RI, Kweudjeu A, Melton DA. Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation. Development. 2013 Feb 01; 140(3):675-86. PMID: 23293299.
    Citations: 27     Fields:    Translation:HumansAnimalsCells
  29. Arbab M, Mahony S, Cho H, Chick JM, Rolfe PA, van Hoff JP, Morris VW, Gygi SP, Maas RL, Gifford DK, Sherwood RI. A multi-parametric flow cytometric assay to analyze DNA-protein interactions. Nucleic Acids Res. 2013 Jan; 41(2):e38. PMID: 23143268.
    Citations:    Fields:    Translation:AnimalsCells
  30. Cho LT, Wamaitha SE, Tsai IJ, Artus J, Sherwood RI, Pedersen RA, Hadjantonakis AK, Niakan KK. Conversion from mouse embryonic to extra-embryonic endoderm stem cells reveals distinct differentiation capacities of pluripotent stem cell states. Development. 2012 Aug; 139(16):2866-77. PMID: 22791892; PMCID: PMC3403099.
    Citations: 41     Fields:    Translation:AnimalsCells
  31. Kim BM, Thier MC, Oh S, Sherwood R, Kanellopoulou C, Edenhofer F, Choi MY. MicroRNAs are indispensable for reprogramming mouse embryonic fibroblasts into induced stem cell-like cells. PLoS One. 2012; 7(6):e39239. PMID: 22737231.
    Citations: 15     Fields:    Translation:HumansAnimalsCells
  32. Hashimoto T, Jaakkola T, Sherwood R, Mazzoni EO, Wichterle H, Gifford D. Lineage-based identification of cellular states and expression programs. Bioinformatics. 2012 Jun 15; 28(12):i250-7. PMID: 22689769.
    Citations: 1     Fields:    Translation:Animals
  33. Mou H, Zhao R, Sherwood R, Ahfeldt T, Lapey A, Wain J, Sicilian L, Izvolsky K, Musunuru K, Cowan C, Rajagopal J. Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell Stem Cell. 2012 Apr 06; 10(4):385-97. PMID: 22482504.
    Citations: 131     Fields:    Translation:HumansAnimalsCells
  34. Sherwood RI, Maehr R, Mazzoni EO, Melton DA. Wnt signaling specifies and patterns intestinal endoderm. Mech Dev. 2011 Sep-Dec; 128(7-10):387-400. PMID: 21854845; PMCID: PMC3223331.
    Citations: 55     Fields:    Translation:AnimalsCells
  35. Niakan KK, Ji H, Maehr R, Vokes SA, Rodolfa KT, Sherwood RI, Yamaki M, Dimos JT, Chen AE, Melton DA, McMahon AP, Eggan K. Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal. Genes Dev. 2010 Feb 01; 24(3):312-26. PMID: 20123909.
    Citations: 134     Fields:    Translation:AnimalsCells
  36. Sherwood RI, Chen TY, Melton DA. Transcriptional dynamics of endodermal organ formation. Dev Dyn. 2009 Jan; 238(1):29-42. PMID: 19097184.
    Citations: 92     Fields:    Translation:AnimalsCells
  37. Anderson WJ, Zhou Q, Alcalde V, Kaneko OF, Blank LJ, Sherwood RI, Guseh JS, Rajagopal J, Melton DA. Genetic targeting of the endoderm with claudin-6CreER. Dev Dyn. 2008 Feb; 237(2):504-12. PMID: 18213590; PMCID: PMC2665265.
    Citations: 29     Fields:    Translation:Animals
  38. Sherwood RI, Jitianu C, Cleaver O, Shaywitz DA, Lamenzo JO, Chen AE, Golub TR, Melton DA. Prospective isolation and global gene expression analysis of definitive and visceral endoderm. Dev Biol. 2007 Apr 15; 304(2):541-55. PMID: 17328885.
    Citations: 60     Fields:    Translation:AnimalsCells
  39. Sherwood RI, Wagers AJ. Harnessing the potential of myogenic satellite cells. Trends Mol Med. 2006 May; 12(5):189-92. PMID: 16595190.
    Citations: 2     Fields:    Translation:AnimalsCells
  40. Sherwood RI, Christensen JL, Conboy IM, Conboy MJ, Rando TA, Weissman IL, Wagers AJ. Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell. 2004 Nov 12; 119(4):543-54. PMID: 15537543.
    Citations: 200     Fields:    Translation:AnimalsCells
  41. Sherwood RI, Christensen JL, Weissman IL, Wagers AJ. Determinants of skeletal muscle contributions from circulating cells, bone marrow cells, and hematopoietic stem cells. Stem Cells. 2004; 22(7):1292-304. PMID: 15579647.
    Citations: 23     Fields:    Translation:AnimalsCells
  42. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002 Sep 27; 297(5590):2256-9. PMID: 12215650.
    Citations: 345     Fields:    Translation:AnimalsCells
  43. Sherwood RJ. Cause and control: education and training of professional industrial hygienists for 2020. Am Ind Hyg Assoc J. 1992 Jun; 53(6):398-403. PMID: 1605113.
    Citations:    Fields:    Translation:Humans
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.