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 activitiesedit
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.
Referencesedit
^ abc"Whitehead Member Richard Young elected to National Academy of Sciences". Whitehead Institute News Office. May 1, 2012. Retrieved 15 October 2015.
^"Whitehead Institute Member Richard Young elected to National Academy of Medicine". October 21, 2019.
^"Scientific American 50: SA 50 Winners and Contributors". Scientific American. November 12, 2006. Retrieved 15 October 2015.
^"Highly Cited Researchers". Web of Science Group.
^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.
^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. PMC3006442. PMID 16153702.
^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. PMC3640494. PMID 23498934.
^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. PMC3462372. PMID 23021215.
^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. PMC3200295. PMID 17632057.