Research Summary

My research goes back to the early days of recombinant DNA, when it was discovered that cDNA could be made in vitro using mRNA as template, when the first restriction enzymes were had to be purified (and exchanged) before starting your research, and when one did not yet have scenarios on how to express a foreign gene from a plasmid in bacteria. As a graduate student, I initiated research that deviated from the overall scope of the host lab and led to the cDNA cloning and bacterial expression of fibroblast interferon, now known as interferon-β. The impact of this research was very substantial, and occurred at the time that cDNA cloning of some proteins with therapeutic potential led to the formation of the first biotechnology companies. This interferon was then developed as a therapy by Biogen and is now clinically used. I moved in 1981 into Genentech, where I started research that led to the characterization of transforming growth factors, i.e. TGF-α and TGF-β, which rapidly became prototypes for their respective families. TGF-α is a transmembrane growth factor, as are the other growth factors in that family, and was originally thought to only act in carcinomas. My lab had a research program on the biology of TGF-α for more than 20 years. I also showed through cDNA cloning that TGF-β was very different from TGF-α. TGF-β, now known as TGF-β1, is the founding member of a large family of differentiation factors of high relevance in developmental and cancer biology, and immunology.

During the last 30 years, my lab made many key contributions to this now extensive research area on the biology of the TGF-β family. My lab was instrumental in identifying the TGF-β receptors and Smads and the mechanisms of Smad signaling and transcriptional control, and has also been playing a key role in the characterization of non-Smad mechanisms of TGF-β signaling. My lab also discovered that TGF-β induces epithelial-mesenchymal differentiation (which was initially highly controversial), and has been pursuing underlying mechanisms after the TGF-β signaling mediators were identified and starting to be characterized. My lab is seen as a leader in the TGF-β field, having contributed in major ways since its inception. Many mechanistic and conceptual advances in the field originate from my lab.

Research Funding

  • April 1, 2016 - March 31, 2021 - Central role of ShcA in differential TGF-beta signaling, epithelial plasticity and carcinoma cell behavior, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA198179
  • January 1, 2009 - December 31, 2018 - Regulatory non-Smad signaling in TGF-b-induced epithelial-mesenchymal transition, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA136690
  • March 1, 1982 - May 31, 2015 - Bio-Organic Biomedical Mass Spectrometry Resource, Co-Investigator. Sponsor: NIH, Sponsor Award ID: P41RR001614
  • January 1, 1995 - January 31, 2015 - Functional crosstalk of TGF-beta/Smad signaling with methyl transferases, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA063101

Education

University of Louvain, Belgium, Lic.Sc.(M.Sc.), 1974, Zoology
University of Ghent, Belgium, Ph.D., 1981, Molecular Biology

Selected Publications

  1. Budi EH, Schaub JR, Decaris M, Turner S, Derynck R. TGF-ß as a driver of fibrosis: physiological roles and therapeutic opportunities. J Pathol. 2021 Jul; 254(4):358-373.  View on PubMed
  2. Katsuno Y, Derynck R. Epithelial plasticity, epithelial-mesenchymal transition, and the TGF-ß family. Dev Cell. 2021 03 22; 56(6):726-746.  View on PubMed
  3. Derynck R, Turley SJ, Akhurst RJ. TGFß biology in cancer progression and immunotherapy. Nat Rev Clin Oncol. 2021 01; 18(1):9-34.  View on PubMed
  4. Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, Campbell K, Cano A, Casanova J, Christofori G, Dedhar S, Derynck R, Ford HL, Fuxe J, García de Herreros A, Goodall GJ, Hadjantonakis AK, Huang RJY, Kalcheim C, Kalluri R, Kang Y, Khew-Goodall Y, Levine H, Liu J, Longmore GD, Mani SA, Massagué J, Mayor R, McClay D, Mostov KE, Newgreen DF, Nieto MA, Puisieux A, Runyan R, Savagner P, Stanger B, Stemmler MP, Takahashi Y, Takeichi M, Theveneau E, Thiery JP, Thompson EW, Weinberg RA, Williams ED, Xing J, Zhou BP, Sheng G, EMT International Association (TEMTIA) . Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2020 06; 21(6):341-352.  View on PubMed
  5. Budi EH, Hoffman S, Gao S, Zhang YE, Derynck R. Integration of TGF-ß-induced Smad signaling in the insulin-induced transcriptional response in endothelial cells. Sci Rep. 2019 11 18; 9(1):16992.  View on PubMed
  6. Derynck R, Weinberg RA. EMT and Cancer: More Than Meets the Eye. Dev Cell. 2019 05 06; 49(3):313-316.  View on PubMed
  7. Duan D, Derynck R. Transforming growth factor-ß (TGF-ß)-induced up-regulation of TGF-ß receptors at the cell surface amplifies the TGF-ß response. J Biol Chem. 2019 05 24; 294(21):8490-8504.  View on PubMed
  8. Katsuno Y, Meyer DS, Zhang Z, Shokat KM, Akhurst RJ, Miyazono K, Derynck R. Chronic TGF-ß exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition. Sci Signal. 2019 02 26; 12(570).  View on PubMed
  9. Derynck R, Budi EH. Specificity, versatility, and control of TGF-ß family signaling. Sci Signal. 2019 02 26; 12(570).  View on PubMed
  10. Budi EH, Mamai O, Hoffman S, Akhurst RJ, Derynck R. Enhanced TGF-ß Signaling Contributes to the Insulin-Induced Angiogenic Responses of Endothelial Cells. iScience. 2019 Jan 25; 11:474-491.  View on PubMed
  11. Katsuno Y, Qin J, Oses-Prieto J, Wang H, Jackson-Weaver O, Zhang T, Lamouille S, Wu J, Burlingame A, Xu J, Derynck R. Arginine methylation of SMAD7 by PRMT1 in TGF-ß-induced epithelial-mesenchymal transition and epithelial stem-cell generation. J Biol Chem. 2018 08 24; 293(34):13059-13072.  View on PubMed
  12. Du D, Katsuno Y, Meyer D, Budi EH, Chen SH, Koeppen H, Wang H, Akhurst RJ, Derynck R. Smad3-mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial-mesenchymal transition. EMBO Rep. 2018 01; 19(1):135-155.  View on PubMed
  13. Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA. Fibroblast-specific inhibition of TGF-ß1 signaling attenuates lung and tumor fibrosis. J Clin Invest. 2017 Oct 02; 127(10):3675-3688.  View on PubMed
  14. Budi EH, Duan D, Derynck R. Transforming Growth Factor-ß Receptors and Smads: Regulatory Complexity and Functional Versatility. Trends Cell Biol. 2017 09; 27(9):658-672.  View on PubMed
  15. Kime C, Sakaki-Yumoto M, Goodrich L, Hayashi Y, Sami S, Derynck R, Asahi M, Panning B, Yamanaka S, Tomoda K. Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program. Proc Natl Acad Sci U S A. 2016 11 01; 113(44):12478-12483.  View on PubMed
  16. Moses HL, Roberts AB, Derynck R. The Discovery and Early Days of TGF-ß: A Historical Perspective. Cold Spring Harb Perspect Biol. 2016 07 01; 8(7).  View on PubMed
  17. Morikawa M, Derynck R, Miyazono K. TGF-ß and the TGF-ß Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harb Perspect Biol. 2016 May 02; 8(5).  View on PubMed
  18. Budi EH, Xu J, Derynck R. Regulation of TGF-ß Receptors. Methods Mol Biol. 2016; 1344:1-33.  View on PubMed
  19. Muthusamy BP, Budi EH, Katsuno Y, Lee MK, Smith SM, Mirza AM, Akhurst RJ, Derynck R. ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-ß-Induced Smad Activation. PLoS Biol. 2015 Dec; 13(12):e1002325.  View on PubMed
  20. Budi EH, Muthusamy BP, Derynck R. The insulin response integrates increased TGF-ß signaling through Akt-induced enhancement of cell surface delivery of TGF-ß receptors. Sci Signal. 2015 Sep 29; 8(396):ra96.  View on PubMed

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