Richard A. Young Explained

Richard Young
Birth Name:Richard Allen Young
Birth Date:12 March 1954
Birth Place:Pittsburgh, Pennsylvania, United States
Field:Genetics
Genomics
Molecular Biology
Cancer
Doctoral Advisor:Joan A. Steitz

Richard Allen Young (born March 12, 1954) is an American geneticist, a Member of Whitehead Institute, and a professor of biology at the Massachusetts Institute of Technology.[1] He is a pioneer in the systems biology of gene control who has developed genomics technologies and concepts key to understanding gene control in human health and disease. He has served as an advisor to the World Health Organization and the National Institutes of Health. He is a member of the National Academy of Sciences and the National Academy of Medicine.[2] Scientific American has recognized him as one of the top 50 leaders in science, technology and business.[3] Young is among the most Highly Cited Researchers in his field.[4]

Education

Young was educated at Indiana University (Bachelor of Science, 1975) and Yale University (PhD, 1979).[5]

Research and career

Young has made major contributions to the understanding of gene control in human development and disease. He discovered that a small set of human embryonic stem cell master transcription factors form a core regulatory circuitry that controls the gene expression program of these cells.[6] This concept of core regulatory circuitry helps guide current efforts to understand gene control, to develop reprogramming protocols for other human cell types and to understand how gene dysregulation contributes to disease.[7]

Young has introduced the concept of transcriptional amplification and described how much of the gene control program in cancer cells is amplified by oncogenic transcription factors such as c-MYC.[8] According to Young, most genes experience transcription initiation,[9] but it is the control of transcription elongation that plays key roles in cell control in health and disease.[10]

Young discovered that large clusters of gene control elements, called super-enhancers, regulate genes that play prominent roles in cell identity.[11] Furthermore, Young showed that disease-associated human genome variation occurs frequently in these super-enhancers[12] and that cancer cell super-enhancers are especially vulnerable to certain transcriptional drugs.[13]

Young has proposed that control of gene expression occurs within insulated neighborhoods, which are structural DNA loops that contain enhancers and their target genes.[14] [15] [16] He has further shown that disruption of these neighborhoods in disease contributes to gene dysregulation.[17] [18]

Young and his colleagues have proposed that regulation of genes occurs in nuclear bodies called biomolecular condensates.[19] These condensates compartmentalize and concentrate the diverse biomolecules needed for proper regulation of gene expression.[20] [21] [22] [23] Young recently discovered that cancer drugs are concentrated in cellular condensates and has proposed that this pharmacodynamic behavior contributes to optimal drug action.[24]

Other activities

Young is also an educator, entrepreneur and aviator. He teaches three courses at MIT, “COVID-19, SARS-CoV-2 and the Pandemic”, "Cell Biology: Structure and Functions of the Nucleus" and "Topics of Mammalian Development and Genetics", and guest lectures at numerous universities and research institutes worldwide.[25] [26] [27] Young has founded multiple companies in the biotechnology industry, including Syros Pharmaceuticals, Inc., CAMP4 Therapeutics, Omega Therapeutics and Dewpoint Therapeutics. He holds a commercial pilot license and is a member of the Aircraft Owners and Pilots Association.

Notes and References

  1. News: Whitehead Member Richard Young elected to National Academy of Sciences. 15 October 2015. Whitehead Institute News Office. May 1, 2012.
  2. News: Whitehead Institute Member Richard Young elected to National Academy of Medicine . October 21, 2019.
  3. News: Scientific American 50: SA 50 Winners and Contributors. 15 October 2015. Scientific American. November 12, 2006.
  4. Web site: Highly Cited Researchers . Web of Science Group.
  5. PhD . Richard Allen. Young . Regulatory signals in ribosomal RNA operons of Escherichia coli . Yale University . 1979 . 638423416 . 10079/bibid/9851541. .
  6. Boyer. LA. Lee. TI. Cole. MF. Johnstone. SE. Levine. SS. Zucker. JP. Guenther. MG. Kumar. RM. Murray. HL. Jenner. RG. Gifford. DK. Melton. DA. Jaenisch. R. Young. RA. Core transcriptional regulatory circuitry in human embryonic stem cells.. Cell. 23 September 2005. 122. 6. 947–56. 16153702. 10.1016/j.cell.2005.08.020. 3006442.
  7. Transcriptional regulation and its misregulation in disease. Lee. TI. 2013. Cell. 10.1016/j.cell.2013.02.014. 23498934. Young. RA. 6. 1237–1251. 3640494. 152.
  8. Transcriptional amplification in tumor cells with elevated c-Myc. Lin. CY. 28 September 2012. Cell. 10.1016/j.cell.2012.08.026. 23021215. Lovén. J. Rahl. PB. Paranal. RM. Burge. JE. CB. Bradner. Lee. TI. Young. RA. 1. 151. 56–67. 3462372.
  9. Guenther. MG. Levine. SS. Boyer. LA. Jaenisch. R. Young. RA. A chromatin landmark and transcription initiation at most promoters in human cells.. Cell. 13 July 2007. 130. 1. 77–88. 17632057. 10.1016/j.cell.2007.05.042. 3200295.
  10. Rahl. PB. Lin. CY. Seila. AC. Flynn. RA. McCuine. S. Burge. CB. Sharp. PA. Young. RA. c-Myc regulates transcriptional pause release.. Cell. 30 April 2010. 141. 3. 432–45. 20434984. 10.1016/j.cell.2010.03.030. 2864022.
  11. Whyte. WA. Orlando. DA. Hnisz. D. Abraham. BJ. Lin. CY. Kagey. MH. Rahl. PB. Lee. TI. Young. RA. Master transcription factors and mediator establish super-enhancers at key cell identity genes.. Cell. 11 April 2013. 153. 2. 307–19. 23582322. 10.1016/j.cell.2013.03.035. 3653129.
  12. Super-enhancers in the control of cell identity and disease. Hnisz. D. 2013. Cell. 10.1016/j.cell.2013.09.053. 24119843. Lau. A. Saint-André. V. Sigova. AA. Hoke. HA. Lee. TI. Young. Abraham. BJ. RA. 4. 934–947. 3841062. 155.
  13. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Lovén. J. 2013. Cell. 10.1016/j.cell.2013.03.036. 23582323. Hoke. HA. Lin. CY. Lau. CR. DA. RA. A. Orlando. Vakoc. Bradner. JE. Lee. TI. Young. 153. 2. 320–334. 3760967.
  14. Dowen. JM. Fan. ZP. Hnisz. D. Ren. G. Abraham. BJ. Zhang. LN. Weintraub. AS. Schuijers. J. Lee. TI. Zhao. K. Young. RA. Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes.. Cell. 9 October 2014. 159. 2. 374–87. 25303531. 10.1016/j.cell.2014.09.030. 4197132.
  15. Ji. X. Dadon. DB. Powell. BE. Fan. ZP. Borges-Rivera. D. Shachar. S. Weintraub. AS. Hnisz. D. Pegoraro. G. Lee. TI. Misteli. T. Jaenisch. R. Young. RA. 3D Chromosome Regulatory Landscape of Human Pluripotent Cells.. Cell Stem Cell. 4 February 2016. 18. 2. 262–75. 26686465. 10.1016/j.stem.2015.11.007. 4848748.
  16. Hnisz. D. Day. DS. Young. RA. 2016. Insulated neighborhoods: structural and functional units of mammalian gene control. Cell. 167. 5. 1188–1200. 10.1016/j.cell.2016.10.024. 5125522. 27863240.
  17. Hnisz. D. Weintraub. AS. Day. DS. Valton. AL. Bak. RO. Li. CH. Goldmann. J. Lajoie. BR. Fan. ZP. Sigova. AA. Reddy. J. Borges-Rivera. D. Lee. TI. Jaenisch. R. Porteus. MH. Dekker. J. Young. RA. Activation of proto-oncogenes by disruption of chromosome neighborhoods.. Science. 25 March 2016. 351. 6280. 1454–8. 26940867. 10.1126/science.aad9024. 4884612. 2016Sci...351.1454H.
  18. News: A Family's Shared Defect Sheds Light on the Human Genome. Angier. Natalie. The New York Times. January 9, 2017.
  19. Hnisz . D . Shrinivas . K . Young . RA . Chakraborty . AK . Sharp . PA . A Phase Separation Model for Transcriptional Control . Cell . 23 March 2017 . 169 . 1 . 13–23 . 10.1016/j.cell.2017.02.007 . 28340338 . 5432200.
  20. Boija . A . Klein . IA . Sabari . BR . Dall'Agnese . A . Coffey . EL . Zamudio . AV . Li . CH . Shrinivas . K . Manteiga . JC . Hannett . NM . Abraham . BJ . Afeyan . LK . Guo . YE . Rimel . JK . Fant . CB . Schuijers . J . Lee . TI . Taatjes . DJ . Young . RA . Transcription factors activate genes through the phase separation capacity of their activation domains . Cell . 13 December 2018 . 175 . 7 . 1842–1855 . 10.1016/j.cell.2018.10.042 . 30449618 . 6295254.
  21. Sabari . BR . Dall'Agnese . A . Boija . A . Klein . IA . Coffey . EL . Shrinivas . K . Abraham . BJ . Hannett . NM . Zamudio . AV . Manteiga . JC . Li . CH . Day . DS . Schuijers . J . Vasile . E . Malik . S . Hnisz . D . Lee . TI . Cisse . II . Roeder . RG . Sharp . PA . Chakraborty . AK . Young . RA . Coactivator condensation at super-enhancers links phase separation and gene control . Science . 27 July 2018 . 361 . 6400 . 10.1126/science.aar3958 . 29930091 . 6092193 . eaar3958.
  22. Guo . YE . Manteiga . JC . Henninger . JE . Sabari . BR . Dall'Agnese . A . Hannnett . NM . Spille . JH . Afeyan . LK . Zamudio . AV . Shrinivas . K . Abraham . BJ . Boija . A . Decker . TM . Rimel . JK . Fant . CB . Lee . TI . Cisse . II . Sharp . PA . Taatjes . DJ . Young . RA . Pol II phosphorylation regulates a switch between transcriptional and splicing condensates . Nature . August 2019 . 572 . 7770 . 543–548 . 10.1038/s41586-019-1464-0 . 31391587 . 6706314. 2019Natur.572..543G .
  23. Daneshvar K, Ardehali MB, Klein IA, Hsieh FK, Kratkiewicz AJ, Mahpour A . etal. lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation. . Nat Cell Biol . 2020 . 22 . 10 . 1211–1222 . 32895492 . 10.1038/s41556-020-0572-2 . 8008247 .
  24. Klein . I.A. . Boija . A. . Afeyan . L.K. . Hawken . S.W. . Fan . M. . Dall'Agnese . A. . Oksuz . O. . Henninger . J.E. . Shrinivas . K. . Sabari . B.R. . Sagi . I. . Clark . V.E. . Platt . J.M. . Kar . M. . McCall . P.M. . Zamudio . A.V. . Manteiga . J.C. . Coffey . E.L. . Li . C.H. . Hannett . N.M. . Guo . Y.E. . Decker . T.M. . Lee . T.I. . Zhang . T. . Weng . J.K. . Taatjes . D.J. . Chakraborty . A. . Sharp . P.A. . Chang . Y.T. . Hyman . A.A. . Gray . N.S. . Young . R.A. . Partitioning of cancer therapeutics in nuclear condensates . Science . 2020 . 368 . 6497 . 1454–1458 . 10.1126/science.aaz4427 . 26940867. 7735713 . 2020Sci...368.1386K .
  25. Web site: CSHL Keynote: Dr Richard Young, Whitehead Institute for Biomedical Research Mass. Institute of Tech. Oct 31, 2013. Cold Spring Harbor Laboratory.
  26. Web site: Roles for Transcriptional Super-Enhancers in Cell Identity and Disease. November 21, 2013. NIH Center for Information Technology.
  27. Web site: CSHL 2015 Symposium Interview Series with Richard Young. May 30, 2015. Cold Spring Harbor Laboratory.

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