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Kenneth S. Zaret (born March 7, 1955) is a professor in the Department of Cell and Developmental Biology at the Perelman School of Medicine, University of Pennsylvania, and Director of the Institute for Regenerative Medicine at UPenn. He is a recipient of the Hans Popper Basic Science Award from the American Association for the Study of Liver Diseases and the American Liver Foundation, a fellow of the American Association for the Advancement of Science, and a member of the American Academy of Arts and Sciences, the European Molecular Biology Organization, and the National Academy of Sciences.

Career

Zaret developed an interest in the natural world when he was growing up, and while in high school gained a fellowship from the National Science Foundation to do some research at a medical school in Philadelphia. This introduced him to laboratory science, and eventually to biology and biochemistry at college. Zaret gained his BA in Biology and then a PhD in Biophysics at the University of Rochester. After postdoctoral research at the University of California, San Francisco, Zaret moved to Brown University in 1986, where he worked first in the Biochemistry section, and later in the Department of Molecular Biology, Cell Biology, and Biochemistry at Brown University Medical School. In 1999, Zaret moved to the Basic Science Division at the Fox Chase Cancer Center in Philadelphia.

Research

As a graduate student with Fred Sherman at the University of Rochester School of Medicine (1977-1982), Zaret discovered that when genes in DNA are transcribed into messenger RNA (mRNA), signals in the DNA cause a coupled termination of transcription and processing of the mRNA by polyadenylation. As a postdoctoral fellow with Keith Yamamoto at the University of California, San Francisco (1982-1985), Zaret discovered that when the steroid receptor for glucocorticoid becomes activated by hormone, the receptor loosens up the local chromosome structure at target genes that then become activated.

Zaret's laboratory investigates the ways that genes are activated and different cell types are specified in embryonic development, regenerating tissues, and disease. His group initially focused on the dynamics in cell signaling, gene regulatory proteins, and chromosome structure in the early mammalian embryo, in the development of the liver. His laboratory discovered embryonic signals that induce the formation of the liver, that there is a bipotential precursor population in the embryo for the liver and pancreas, and that primitive blood vessel cells, before they form blood vessels, signal to early liver cells to develop morphologically into the liver. The findings from his laboratory have been used by other laboratories to engineer new liver cells and liver tissue from stem cells.

His laboratory discovered and named pioneer transcription factors that can bind to compacted chromosome domains harboring silent genes, and that enable cooperative events with other proteins to allow silent genes to turn on. The mechanism of targeting of silent, compacted chromosome domains by pioneer factors has since been found by many laboratories to control the earliest stages of embryonic development and enable cell fate switching in development, regeneration, and human cancers.

Zaret's laboratory revealed an unexpectedly dynamic nature of the most compacted form of chromosome structure, called heterochromatin, during embryonic development. They also found that the H3K9me3 subtype of heterochromatin is the most repressive form to overcome when reprogramming cell fates. These findings can be applied to controlling cell fates at will for modeling human disease and developing cell-based therapies.

References

1. "Elected Fellows". aaas.org. Retrieved June 30, 2023.
2. "Members Elected in 2021, by Class & Section". amacad.org. 6 December 2021. Retrieved June 30, 2023.
3. "EMBO elects 67 new members and associate members". embo.org. 6 July 2022. Retrieved June 30, 2023.
4. "Four from Penn elected to the National Academy of Sciences". upenn.edu. 3 May 2023. Retrieved June 30, 2023.
5. ^ Senior, Kathryn (2010). "An interview with Ken Zaret". Development. 137: 3151–3152.
6. "Kenneth S. Zaret". www.nasonline.org.
7. "DNA sequence required for efficient transcription termination in yeast" (PDF). Cell. March 1982. Retrieved June 30, 2023.
8. "Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element" (PDF). Cell. August 1984. Retrieved June 30, 2023.
9. Zaret, Kenneth S.; Grompe, Markus (December 5, 2008). "Generation and Regeneration of Cells of the Liver and Pancreas". Science. 322 (5907): 1490–1494. Bibcode:2008Sci...322.1490Z. doi:10.1126/science.1161431. PMC 2641009. PMID 19056973.
10. Jung, Joonil; Zheng, Minghua; Goldfarb, Mitchell; Zaret, Kenneth S. (June 18, 1999). "Initiation of Mammalian Liver Development from Endoderm by Fibroblast Growth Factors". Science. 284 (5422): 1998–2003. doi:10.1126/science.284.5422.1998. PMID 10373120. Retrieved June 30, 2023.
11. "A bipotential precursor population for pancreas and liver within the embryonic endoderm". Development. March 15, 2001. Retrieved June 30, 2023.
12. Matsumoto, Kunio; Yoshitomi, Hideyuki; Rossant, Janet; Zaret, Kenneth S. (September 27, 2001). "Liver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function". Science. 294 (5542): 559–563. Bibcode:2001Sci...294..559M. doi:10.1126/science.1063889. PMID 11577199. S2CID 44496195. Retrieved June 30, 2023.
13. Thompson, Wendy L.; Takebe, Takanori (January 10, 2021). "Human liver model systems in a dish". Development, Growth & Differentiation. 63 (1): 47–58. doi:10.1111/dgd.12708. PMC 7940568. PMID 33423319.
14. Cirillo, Lisa Ann; Lin, Frank Robert; Cuesta, Isabel; Friedman, Dara; Jarnik, Michal; Zaret, Kenneth S. (February 2002). "Opening of Compacted Chromatin by Early Developmental Transcription Factors HNF3 (FoxA) and GATA-4". Molecular Cell. 9 (2): 279–289. doi:10.1016/S1097-2765(02)00459-8. PMID 11864602. Retrieved June 30, 2023.
15. Zaret, Kenneth S. (September 4, 2020). "Pioneer Transcription Factors Initiating Gene Network Changes". Annual Review of Genetics. 54: 367–385. doi:10.1146/annurev-genet-030220-015007. PMC 7900943. PMID 32886547.
16. Nicetto, Dario; Donahue, Greg; Jain, Tanya; Peng, Tao; Sidoli, Simone; Sheng, Lihong; Montavon, Thomas; Becker, Justin S.; Grindheim, Jessica M.; Blahnik, Kimberly; Garcia, Benjamin A.; Tan, Kai; Bonasio, Roberto; Jenuwein, Thomas; Zaret, Kenneth S. (January 3, 2019). "H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification". Science. 363 (6424): 294–297. Bibcode:2019Sci...363..294N. doi:10.1126/science.aau0583. PMC 6664818. PMID 30606806.
17. McCarthy, Ryan L.; Kaeding, Kelsey E.; Keller, Samuel H.; Zhong, Yu; Xu, Liqin; Hsieh, Antony; Hou, Yong; Donahue, Greg; Becker, Justin S.; Alberto, Oscar; Lim, Bomyi; Zaret, Kenneth S. (August 5, 2021). "Diverse heterochromatin-associated proteins repress distinct classes of genes and repetitive elements". Nature Cell Biology. 23 (8): 905–914. doi:10.1038/s41556-021-00725-7. PMC 9248069. PMID 34354237.

• Living people
• Fellows of the American Association for the Advancement of Science
• Fellows of the American Academy of Arts and Sciences
• Members of the European Molecular Biology Organization
• Members of the United States National Academy of Sciences
• 21st-century American biologists
• University of Rochester alumni
• University of Pennsylvania faculty
• 1955 births