{{short description|American biologist}}
{{Infobox scientist | name = Kenneth S. Zaret | birth_name = | birth_date = March 7, 1955 | birth_place = | death_date = | death_place = | fields = Biology | workplaces = University of California, San Francisco (1982-1985)<br>Brown University (1986-1999)<br>University of Pennsylvania (1999-) | alma_mater = University of Rochester }}
'''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,<ref>{{Cite web |url=https://www.aaas.org/fellows/listing |title=Elected Fellows |publisher=aaas.org |accessdate=June 30, 2023}}</ref> and a member of the American Academy of Arts and Sciences,<ref>{{Cite web |url=https://www.amacad.org/news/members-elected-2021-class-section |title=Members Elected in 2021, by Class & Section |date=6 December 2021 |publisher=amacad.org |accessdate= June 30, 2023}}</ref> the European Molecular Biology Organization,<ref>{{Cite web |url=https://www.embo.org/press-releases/embo-elects-67-new-members-and-associate-members/ |title=EMBO elects 67 new members and associate members |date=6 July 2022 |publisher=embo.org |accessdate= June 30, 2023}}</ref> and the National Academy of Sciences.<ref>{{Cite web |url=https://penntoday.upenn.edu/news/four-penn-elected-national-academy-sciences |title=Four from Penn elected to the National Academy of Sciences |date=3 May 2023 |publisher=upenn.edu |accessdate= June 30, 2023}}</ref>
==Career== Zaret developed an interest in the natural world when he was growing up, and while in high school, he 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.<ref name="auto">{{cite journal|url=https://journals.biologists.com/dev/article/137/19/3151/44013/An-interview-with-Ken-Zaret|title=An interview with Ken Zaret|last=Senior|first=Kathryn|journal=Development|volume=137|pages=3151–3152|year=2010|issue=19 |doi=10.1242/dev.055434 |pmid=20823060 }}</ref> 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.<ref name="auto"/><ref>{{Cite web|url=https://www.nasonline.org/member-directory/members/20056769.html|title=Kenneth S. Zaret|website=www.nasonline.org}}</ref>
== 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.<ref>{{Cite web |url=https://www.cell.com/cell/pdf/0092-8674(82)90211-2.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2F0092867482902112%3Fshowall%3Dtrue |title=DNA sequence required for efficient transcription termination in yeast |publisher=Cell |date= March 1982 |accessdate= June 30, 2023}}</ref> 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.<ref>{{Cite web |url=https://www.cell.com/cell/pdf/0092-8674(84)90523-3.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2F0092867484905233%3Fshowall%3Dtrue |title=Reversible and persistent changes in chromatin structure accompany activation of a glucocorticoid-dependent enhancer element |publisher=Cell |date= August 1984 |accessdate= June 30, 2023}}</ref>
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 of cell signaling, gene regulatory proteins, and chromosome structure in the early mammalian embryo, and the development of the liver.<ref>{{Cite journal |title=Generation and Regeneration of Cells of the Liver and Pancreas |journal=Science |date= December 5, 2008 |doi=10.1126/science.1161431 |last1=Zaret |first1=Kenneth S. |last2=Grompe |first2=Markus |volume=322 |issue=5907 |pages=1490–1494 |pmid=19056973 |pmc=2641009 |bibcode=2008Sci...322.1490Z }}</ref> His laboratory discovered embryonic signals that induce the formation of the liver,<ref>{{Cite journal |url=https://www.science.org/doi/10.1126/science.284.5422.1998?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed |title=Initiation of Mammalian Liver Development from Endoderm by Fibroblast Growth Factors |journal=Science |date=June 18, 1999 |doi=10.1126/science.284.5422.1998 |accessdate= June 30, 2023 |last1=Jung |first1=Joonil |last2=Zheng |first2=Minghua |last3=Goldfarb |first3=Mitchell |last4=Zaret |first4=Kenneth S. |volume=284 |issue=5422 |pages=1998–2003 |pmid=10373120 |url-access=subscription }}</ref> that there is a bipotential precursor population in the embryo for the liver and pancreas,<ref>{{Cite web |url=https://journals.biologists.com/dev/article/128/6/871/41526/A-bipotential-precursor-population-for-pancreas |title=A bipotential precursor population for pancreas and liver within the embryonic endoderm |publisher=Development |date= March 15, 2001 |accessdate= June 30, 2023}}</ref> and that primitive blood vessel cells, before they form blood vessels, signal to early liver cells to develop morphologically into the liver.<ref>{{Cite journal |url=https://www.science.org/doi/10.1126/science.1063889?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed |title=Liver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function |journal=Science |date=September 27, 2001 |doi=10.1126/science.1063889 |accessdate= June 30, 2023 |last1=Matsumoto |first1=Kunio |last2=Yoshitomi |first2=Hideyuki |last3=Rossant |first3=Janet |last4=Zaret |first4=Kenneth S. |volume=294 |issue=5542 |pages=559–563 |pmid=11577199 |bibcode=2001Sci...294..559M |s2cid=44496195 |url-access=subscription }}</ref> The findings from his laboratory have been used by other laboratories to engineer new liver cells and liver tissue from stem cells.<ref>{{Cite journal |title=Human liver model systems in a dish |journal=Development, Growth & Differentiation |date= January 10, 2021|doi=10.1111/dgd.12708 |last1=Thompson |first1=Wendy L. |last2=Takebe |first2=Takanori |volume=63 |issue=1 |pages=47–58 |pmid=33423319 |pmc=7940568 }}</ref>
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.<ref>{{Cite journal |title=Opening of Compacted Chromatin by Early Developmental Transcription Factors HNF3 (FoxA) and GATA-4 |journal=Molecular Cell |date=February 2002 |doi=10.1016/S1097-2765(02)00459-8 |last1=Cirillo |first1=Lisa Ann |last2=Lin |first2=Frank Robert |last3=Cuesta |first3=Isabel |last4=Friedman |first4=Dara |last5=Jarnik |first5=Michal |last6=Zaret |first6=Kenneth S. |volume=9 |issue=2 |pages=279–289 |pmid=11864602 |doi-access=free }}</ref> 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.<ref>{{Cite journal |title=Pioneer Transcription Factors Initiating Gene Network Changes |journal=Annual Review of Genetics |date=September 4, 2020 |doi=10.1146/annurev-genet-030220-015007 |last1=Zaret |first1=Kenneth S. |volume=54 |pages=367–385 |pmid=32886547 |pmc=7900943 }}</ref>
Zaret's laboratory revealed an unexpectedly dynamic nature of the most compacted form of chromosome structure, called heterochromatin, during embryonic development.<ref>{{Cite journal |title=H3K9me3-heterochromatin loss at protein-coding genes enables developmental lineage specification |journal= Science |date=January 3, 2019 |doi=10.1126/science.aau0583 |last1=Nicetto |first1=Dario |last2=Donahue |first2=Greg |last3=Jain |first3=Tanya |last4=Peng |first4=Tao |last5=Sidoli |first5=Simone |last6=Sheng |first6=Lihong |last7=Montavon |first7=Thomas |last8=Becker |first8=Justin S. |last9=Grindheim |first9=Jessica M. |last10=Blahnik |first10=Kimberly |last11=Garcia |first11=Benjamin A. |last12=Tan |first12=Kai |last13=Bonasio |first13=Roberto |last14=Jenuwein |first14=Thomas |last15=Zaret |first15=Kenneth S. |volume=363 |issue=6424 |pages=294–297 |pmid=30606806 |pmc=6664818 |bibcode=2019Sci...363..294N }}</ref> They also found that the H3K9me3 subtype of heterochromatin is the most repressive form to overcome when reprogramming cell fates.<ref>{{Cite journal |title=Diverse heterochromatin-associated proteins repress distinct classes of genes and repetitive elements |journal=Nature Cell Biology |date=August 5, 2021 |doi=10.1038/s41556-021-00725-7 |last1=McCarthy |first1=Ryan L. |last2=Kaeding |first2=Kelsey E. |last3=Keller |first3=Samuel H. |last4=Zhong |first4=Yu |last5=Xu |first5=Liqin |last6=Hsieh |first6=Antony |last7=Hou |first7=Yong |last8=Donahue |first8=Greg |last9=Becker |first9=Justin S. |last10=Alberto |first10=Oscar |last11=Lim |first11=Bomyi |last12=Zaret |first12=Kenneth S. |volume=23 |issue=8 |pages=905–914 |pmid=34354237 |pmc=9248069 }}</ref> These findings can be applied to controlling cell fates at will for modeling human disease and developing cell-based therapies.
==References== {{Reflist}}
{{Authority control}}
{{DEFAULTSORT:Zaret, Kenneth}} Category:Living people Category:Fellows of the American Association for the Advancement of Science Category:Fellows of the American Academy of Arts and Sciences Category:Members of the European Molecular Biology Organization Category:Members of the United States National Academy of Sciences Category:21st-century American biologists Category:University of Rochester alumni Category: University of Pennsylvania faculty Category:1955 births