Richard A. Young

Last updated
Richard Young
Richardyoung hiking.jpg
Born
Richard Allen Young

(1954-03-12) March 12, 1954 (age 69)
Pittsburgh, Pennsylvania, United States
Alma mater
Awards
Scientific career
Fields Genetics
Genomics
Molecular Biology
Cancer
Institutions
Doctoral advisor Joan A. Steitz
Website wi.mit.edu/people/faculty/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]

Contents

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.

Related Research Articles

<span class="mw-page-title-main">Promoter (genetics)</span> Region of DNA encouraging transcription

In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA . Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism.

<span class="mw-page-title-main">Gene expression</span> Conversion of a genes sequence into a mature gene product or products

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in 1958, further developed in his 1970 article, and expanded by the subsequent discoveries of reverse transcription and RNA replication.

<span class="mw-page-title-main">Transcription (biology)</span> Process of copying a segment of DNA into RNA

Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA, while at least 80% of mammalian genomic DNA can be actively transcribed, with the majority of this 80% considered to be ncRNA.

<span class="mw-page-title-main">Enhancer (genetics)</span> DNA sequence that binds activators to increase the likelihood of gene transcription

In genetics, an enhancer is a short region of DNA that can be bound by proteins (activators) to increase the likelihood that transcription of a particular gene will occur. These proteins are usually referred to as transcription factors. Enhancers are cis-acting. They can be located up to 1 Mbp away from the gene, upstream or downstream from the start site. There are hundreds of thousands of enhancers in the human genome. They are found in both prokaryotes and eukaryotes.

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.

<span class="mw-page-title-main">Oct-4</span> Mammalian protein found in Homo sapiens

Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.

<span class="mw-page-title-main">Homeobox protein NANOG</span> Mammalian protein found in humans

Homeobox protein NANOG(hNanog) is a transcriptional factor that helps embryonic stem cells (ESCs) maintain pluripotency by suppressing cell determination factors. hNanog is encoded in humans by the NANOG gene. Several types of cancer are associated with NANOG.

An insulator is a type of cis-regulatory element known as a long-range regulatory element. Found in multicellular eukaryotes and working over distances from the promoter element of the target gene, an insulator is typically 300 bp to 2000 bp in length. Insulators contain clustered binding sites for sequence specific DNA-binding proteins and mediate intra- and inter-chromosomal interactions.

<span class="mw-page-title-main">Interferon regulatory factors</span> Protein family

Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons. Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a structure that binds specifically to the IRF-element (IRF-E) motifs, which is located upstream of the interferon genes. Some viruses have evolved defense mechanisms that regulate and interfere with IRF functions to escape the host immune system. For instance, the remaining parts of the interferon regulatory factor sequence vary depending on the precise function of the protein. The Kaposi sarcoma herpesvirus, KSHV, is a cancer virus that encodes four different IRF-like genes; including vIRF1, which is a transforming oncoprotein that inhibits type 1 interferon activity. In addition, the expression of IRF genes is under epigenetic regulation by promoter DNA methylation.

<span class="mw-page-title-main">CTCF</span> Transcription factor

Transcriptional repressor CTCF also known as 11-zinc finger protein or CCCTC-binding factor is a transcription factor that in humans is encoded by the CTCF gene. CTCF is involved in many cellular processes, including transcriptional regulation, insulator activity, V(D)J recombination and regulation of chromatin architecture.

<span class="mw-page-title-main">Mef2</span> Protein family

In the field of molecular biology, myocyte enhancer factor-2 (Mef2) proteins are a family of transcription factors which through control of gene expression are important regulators of cellular differentiation and consequently play a critical role in embryonic development. In adult organisms, Mef2 proteins mediate the stress response in some tissues. Mef2 proteins contain both MADS-box and Mef2 DNA-binding domains.

<span class="mw-page-title-main">FOXO3</span> Protein-coding gene in the species Homo sapiens

Forkhead box O3, also known as FOXO3 or FOXO3a, is a human protein encoded by the FOXO3 gene.

<span class="mw-page-title-main">DNA damage-inducible transcript 3</span> Human protein and coding gene

DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis and has an important role in the cell's stress response.

<span class="mw-page-title-main">HOXA5</span> Protein-coding gene in humans

Homeobox protein Hox-A5 is a protein that in humans is encoded by the HOXA5 gene.

<span class="mw-page-title-main">SUZ12</span> Protein-coding gene in the species Homo sapiens

Polycomb protein SUZ12 is a protein that in humans is encoded by the SUZ12 gene.

In genetics, a super-enhancer is a region of the mammalian genome comprising multiple enhancers that is collectively bound by an array of transcription factor proteins to drive transcription of genes involved in cell identity. Because super-enhancers are frequently identified near genes important for controlling and defining cell identity, they may thus be used to quickly identify key nodes regulating cell identity.

<span class="mw-page-title-main">Insulated neighborhood</span>

In mammalian biology, insulated neighborhoods are chromosomal loop structures formed by the physical interaction of two DNA loci bound by the transcription factor CTCF and co-occupied by cohesin. Insulated neighborhoods are thought to be structural and functional units of gene control because their integrity is important for normal gene regulation. Current evidence suggests that these structures form the mechanistic underpinnings of higher-order chromosome structures, including topologically associating domains (TADs). Insulated neighborhoods are functionally important in understanding gene regulation in normal cells and dysregulated gene expression in disease.

<span class="mw-page-title-main">Transcriptional amplification</span>

In genetics, transcriptional amplification is the process in which the total amount of messenger RNA (mRNA) molecules from expressed genes is increased during disease, development, or in response to stimuli.

Jeannie T. Lee is a Professor of Genetics at Harvard Medical School and the Massachusetts General Hospital, and a Howard Hughes Medical Institute Investigator. She is known for her work on X-chromosome inactivation and for discovering the functions of a new class of epigenetic regulators known as long noncoding RNAs (lncRNAs), including Xist and Tsix.

A chromatin variant corresponds to a section of the genome that differs in chromatin states across cell types/states within an individual (intra-individual) or between individuals for a given cell type/state (inter-individual). Chromatin variants distinguish DNA sequences that differ in their function in one cell type/state versus another. Chromatin variants are found across the genome, inclusive of repetitive and non-repetitive DNA sequence. Chromatin variants range in sizes. The smallest chromatin variants cover a few hundred DNA base pairs, such as seen at promoters, enhancers or insulators. The largest chromatin variants capture a few thousand DNA base pairs, such as seen at Large Organized Chromatin Lysine domains (LOCKs) and Clusters Of Cis-Regulatory Elements (COREs), such as super-enhancer.

References

  1. 1 2 3 "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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.