Richard A. Young

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.[1] He is a member of the National Academy of Sciences[1] 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]

For other uses, see Richard Young.
Richard Young
Born
Richard Allen Young

(1954-03-12) March 12, 1954
Pittsburgh, Pennsylvania, United States
Alma mater
Awards
Scientific career
FieldsGenetics
Genomics
Molecular Biology
Cancer
Institutions
Doctoral advisorJoan A. Steitz
Websitewi.mit.edu/people/faculty/young

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.

References
  1. "Whitehead Member Richard Young elected to National Academy of Sciences". Whitehead Institute News Office. May 1, 2012. Retrieved 15 October 2015.
  2. "Whitehead Institute Member Richard Young elected to National Academy of Medicine". October 21, 2019.
  3. "Scientific American 50: SA 50 Winners and Contributors". Scientific American. November 12, 2006. Retrieved 15 October 2015.
  4. "Highly Cited Researchers". Web of Science Group.
  5. Young, Richard Allen (1979). Regulatory signals in ribosomal RNA operons of Escherichia coli (PhD thesis). Yale University. hdl:10079/bibid/9851541. OCLC 638423416. ProQuest 303012111.
  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 (23 September 2005). "Core transcriptional regulatory circuitry in human embryonic stem cells". Cell. 122 (6): 947–56. doi:10.1016/j.cell.2005.08.020. PMC 3006442. PMID 16153702.
  7. Lee, TI; Young, RA (2013). "Transcriptional regulation and its misregulation in disease". Cell. 152 (6): 1237–1251. doi:10.1016/j.cell.2013.02.014. PMC 3640494. PMID 23498934.
  8. Lin, CY; Lovén, J; Rahl, PB; Paranal, RM; Burge, CB; Bradner, JE; Lee, TI; Young, RA (28 September 2012). "Transcriptional amplification in tumor cells with elevated c-Myc". Cell. 151 (1): 56–67. doi:10.1016/j.cell.2012.08.026. PMC 3462372. PMID 23021215.
  9. Guenther, MG; Levine, SS; Boyer, LA; Jaenisch, R; Young, RA (13 July 2007). "A chromatin landmark and transcription initiation at most promoters in human cells". Cell. 130 (1): 77–88. doi:10.1016/j.cell.2007.05.042. PMC 3200295. PMID 17632057.
  10. Rahl, PB; Lin, CY; Seila, AC; Flynn, RA; McCuine, S; Burge, CB; Sharp, PA; Young, RA (30 April 2010). "c-Myc regulates transcriptional pause release". Cell. 141 (3): 432–45. doi:10.1016/j.cell.2010.03.030. PMC 2864022. PMID 20434984.
  11. Whyte, WA; Orlando, DA; Hnisz, D; Abraham, BJ; Lin, CY; Kagey, MH; Rahl, PB; Lee, TI; Young, RA (11 April 2013). "Master transcription factors and mediator establish super-enhancers at key cell identity genes". Cell. 153 (2): 307–19. doi:10.1016/j.cell.2013.03.035. PMC 3653129. PMID 23582322.
  12. Hnisz, D; Abraham, BJ; Lau, A; Saint-André, V; Sigova, AA; Hoke, HA; Lee, TI; Young, RA (2013). "Super-enhancers in the control of cell identity and disease". Cell. 155 (4): 934–947. doi:10.1016/j.cell.2013.09.053. PMC 3841062. PMID 24119843.
  13. Lovén, J; Hoke, HA; Lin, CY; Lau, A; Orlando, DA; Vakoc, CR; Bradner, JE; Lee, TI; Young, RA (2013). "Selective inhibition of tumor oncogenes by disruption of super-enhancers". Cell. 153 (2): 320–334. doi:10.1016/j.cell.2013.03.036. PMC 3760967. PMID 23582323.
  14. Dowen, JM; Fan, ZP; Hnisz, D; Ren, G; Abraham, BJ; Zhang, LN; Weintraub, AS; Schuijers, J; Lee, TI; Zhao, K; Young, RA (9 October 2014). "Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes". Cell. 159 (2): 374–87. doi:10.1016/j.cell.2014.09.030. PMC 4197132. PMID 25303531.
  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 (4 February 2016). "3D Chromosome Regulatory Landscape of Human Pluripotent Cells". Cell Stem Cell. 18 (2): 262–75. doi:10.1016/j.stem.2015.11.007. PMC 4848748. PMID 26686465.
  16. Hnisz, D; Day, DS; Young, RA (2016). "Insulated neighborhoods: structural and functional units of mammalian gene control". Cell. 167 (5): 1188–1200. doi:10.1016/j.cell.2016.10.024. PMC 5125522. PMID 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 (25 March 2016). "Activation of proto-oncogenes by disruption of chromosome neighborhoods". Science. 351 (6280): 1454–8. Bibcode:2016Sci...351.1454H. doi:10.1126/science.aad9024. PMC 4884612. PMID 26940867.
  18. Angier, Natalie (January 9, 2017). "A Family's Shared Defect Sheds Light on the Human Genome". The New York Times.
  19. Hnisz, D; Shrinivas, K; Young, RA; Chakraborty, AK; Sharp, PA (23 March 2017). "A Phase Separation Model for Transcriptional Control". Cell. 169 (1): 13–23. doi:10.1016/j.cell.2017.02.007. PMC 5432200. PMID 28340338.
  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 (13 December 2018). "Transcription factors activate genes through the phase separation capacity of their activation domains". Cell. 175 (7): 1842–1855. doi:10.1016/j.cell.2018.10.042. PMC 6295254. PMID 30449618.
  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 (27 July 2018). "Coactivator condensation at super-enhancers links phase separation and gene control". Science. 361 (6400): eaar3958. doi:10.1126/science.aar3958. PMC 6092193. PMID 29930091.
  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 (August 2019). "Pol II phosphorylation regulates a switch between transcriptional and splicing condensates". Nature. 572 (7770): 543–548. Bibcode:2019Natur.572..543G. doi:10.1038/s41586-019-1464-0. PMC 6706314. PMID 31391587.
  23. Daneshvar K, Ardehali MB, Klein IA, Hsieh FK, Kratkiewicz AJ, Mahpour A; et al. (2020). "lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation". Nat Cell Biol. 22 (10): 1211–1222. doi:10.1038/s41556-020-0572-2. PMC 8008247. PMID 32895492.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. (2020). "Partitioning of cancer therapeutics in nuclear condensates". Science. 368 (6497): 1454–1458. Bibcode:2020Sci...368.1386K. doi:10.1126/science.aaz4427. PMC 7735713. PMID 26940867.
  25. "CSHL Keynote: Dr Richard Young, Whitehead Institute for Biomedical Research Mass. Institute of Tech". Cold Spring Harbor Laboratory. Oct 31, 2013.
  26. "Roles for Transcriptional Super-Enhancers in Cell Identity and Disease". NIH Center for Information Technology. November 21, 2013.
  27. "CSHL 2015 Symposium Interview Series with Richard Young". Cold Spring Harbor Laboratory. May 30, 2015.
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