1e
19
1
49
2
2
18
1b
1d
18
32
3b
1d
2 29
1d
25
Kenneth S Zaret, PhD
78
3b
Joseph Leidy Professor
28
a2
3
75
Executive Committee, University of Pennsylvania Center for Molecular Studies in Digestive and Liver Disease
6d
Member, Institute for Diabetes, Obesity and Metabolism
68
Director, The Institute for Regenerative Medicine
11
Department: Cell and Developmental Biology
4
1
23
1f
Graduate Group Affiliations
8
a
b
1d
46
Contact information
5a
4
3
3
1d
5a
Department of Cell and Developmental Biology
30 Smilow Center for Translational Research
4a 3400 Civic Center Blvd., Rm. 9-132
Philadelphia, PA 19104-5157
26
30 Smilow Center for Translational Research
4a 3400 Civic Center Blvd., Rm. 9-132
Philadelphia, PA 19104-5157
2e
Office: 215-573-5813
32 Fax: 215-898-9871
32 Lab: 215-573-5844
18
9b
32 Fax: 215-898-9871
32 Lab: 215-573-5844
18
Email:
zaret@pennmedicine.upenn.edu
12
zaret@pennmedicine.upenn.edu
18
Publications
23 a
3
2
29
23 a
Links
d3 Search PubMed for articles
8e Penn Medicine, Institute for Diabetes, Obesity and Metabolism (IDOM)
95 University of Pennsylvania, Cell and Molecular Biology Graduate Group (CAMB)
7e University of Pennsylvania, DNA Sequencing Facility
8b University of Pennsylvania, Microarray Facility
92 University of Pennsylvania, Proteomics Core Facility
68 Institute for Regenerative Medicine
9f Center for Liver and Digestive Disease, NIDDK
99 University of Pennsylvania School of Medicine, Cell and Developmental Biology
59 Zaret Lab website
7e University of Pennsylvania, Bioinformatics Core
c
4
b
1f
d3 Search PubMed for articles
8e Penn Medicine, Institute for Diabetes, Obesity and Metabolism (IDOM)
95 University of Pennsylvania, Cell and Molecular Biology Graduate Group (CAMB)
7e University of Pennsylvania, DNA Sequencing Facility
8b University of Pennsylvania, Microarray Facility
92 University of Pennsylvania, Proteomics Core Facility
68 Institute for Regenerative Medicine
9f Center for Liver and Digestive Disease, NIDDK
99 University of Pennsylvania School of Medicine, Cell and Developmental Biology
59 Zaret Lab website
7e University of Pennsylvania, Bioinformatics Core
c
13
Education:
21 7 BA 14 (Biology) c
30 University of Rochester, 1977.
21 8 PhD 20 (Biophysics/Genetics) c
3f University of Rochester Medical School, 1982.
c
3
3
3
3
8d
Permanent link21 7 BA 14 (Biology) c
30 University of Rochester, 1977.
21 8 PhD 20 (Biophysics/Genetics) c
3f University of Rochester Medical School, 1982.
c
2 29
21
1e
1d
24
5e
22 Mammalian gene regulation
1d cell differentiation
1c chromatin structure
8
75 Key words: chromatin, gene regulation, transcription, differentiation, liver and pancreas development.
8
26 Description of Research
654 The goal of the laboratory is to understand how genes are activated and different cell types are specified in embryonic development. These processes involve regulatory mechanisms that are used later in life to maintain human health, to respond to tissue damage, and during the initiation of cancers and other human diseases. The laboratory has two general approaches. First, we investigate the molecular signaling pathways that commit an undifferentiated embryonic cell, the endoderm, to a particular cell type fate, using the specification of liver and pancreas cells as a model. In the past year, we developed a fate map of the foregut endoderm in the mouse embryo, we discovered how a gene regulatory protein controls morphogenesis so that endoderm cells are properly positioned to receive organ-inductive signals, and we found distinct roles for blood vessel cells in promoting the growth of liver and pancreatic tissues at the earliest stages of organ development. The second approach of the laboratory is to investigate ways that gene regulatory proteins control the packaging of DNA in the cell nucleus, to control gene activity. Biochemical studies revealed that the regulatory protein FoxA possesses a protein segment that interacts with chromosome structural proteins, or histones, and is necessary for exposing genes sequences in chromosomes that are otherwise hidden by the histone proteins. Understanding how regulatory proteins and cell signals control gene activity and cell type decisions in development will help guide future efforts to control the differentiation and function of cells at will.
8
20 Rotation Projects
a9 1. Biochemical and genetic analysis of cell signaling and transcription factor activation in mouse embryo tissues, during liver and pancreas cell specification.
42 2. Epigenetic regulation of developmental gene expression.
50 3. Mechanisms of transcription factor modulation of chromatin structure.
4f 4. Genetic lineage tracing of different liver and pancreas progenitors.
48 5. Basis for pluripotency reprogramming by transcription factor.
8
1e Lab personnel:
2e Jungsun Kim, Ph.D., Research Associate
34 Makiko I. Doi, Ph.D., Postdoctoral Associate
2f Jonathan Lerner, Postdoctoral Associate
2d Ryan McCarthy, Postdoctoral Associate
37 Gregory Donahue, M.Sc., Computational Biologist
2d Dario Nicetto, Postdoctoral Associate
2b Jessica Grindheim, Graduate Student
27 Kate Palozola, Graduate Student
31 Meilin Fernandez Garcia, Rotation Student
28 Kelsey Kaeding, Rotation Student
2c Katherine Palozola, Graduate Student
2b Naomi Takenaka, Research Specialist
2f Ann O'Brien Jenkins, Research Specialist
26 29
27
Description of Research Expertise
2a Research Interests22 Mammalian gene regulation
1d cell differentiation
1c chromatin structure
8
75 Key words: chromatin, gene regulation, transcription, differentiation, liver and pancreas development.
8
26 Description of Research
654 The goal of the laboratory is to understand how genes are activated and different cell types are specified in embryonic development. These processes involve regulatory mechanisms that are used later in life to maintain human health, to respond to tissue damage, and during the initiation of cancers and other human diseases. The laboratory has two general approaches. First, we investigate the molecular signaling pathways that commit an undifferentiated embryonic cell, the endoderm, to a particular cell type fate, using the specification of liver and pancreas cells as a model. In the past year, we developed a fate map of the foregut endoderm in the mouse embryo, we discovered how a gene regulatory protein controls morphogenesis so that endoderm cells are properly positioned to receive organ-inductive signals, and we found distinct roles for blood vessel cells in promoting the growth of liver and pancreatic tissues at the earliest stages of organ development. The second approach of the laboratory is to investigate ways that gene regulatory proteins control the packaging of DNA in the cell nucleus, to control gene activity. Biochemical studies revealed that the regulatory protein FoxA possesses a protein segment that interacts with chromosome structural proteins, or histones, and is necessary for exposing genes sequences in chromosomes that are otherwise hidden by the histone proteins. Understanding how regulatory proteins and cell signals control gene activity and cell type decisions in development will help guide future efforts to control the differentiation and function of cells at will.
8
20 Rotation Projects
a9 1. Biochemical and genetic analysis of cell signaling and transcription factor activation in mouse embryo tissues, during liver and pancreas cell specification.
42 2. Epigenetic regulation of developmental gene expression.
50 3. Mechanisms of transcription factor modulation of chromatin structure.
4f 4. Genetic lineage tracing of different liver and pancreas progenitors.
48 5. Basis for pluripotency reprogramming by transcription factor.
8
1e Lab personnel:
2e Jungsun Kim, Ph.D., Research Associate
34 Makiko I. Doi, Ph.D., Postdoctoral Associate
2f Jonathan Lerner, Postdoctoral Associate
2d Ryan McCarthy, Postdoctoral Associate
37 Gregory Donahue, M.Sc., Computational Biologist
2d Dario Nicetto, Postdoctoral Associate
2b Jessica Grindheim, Graduate Student
27 Kate Palozola, Graduate Student
31 Meilin Fernandez Garcia, Rotation Student
28 Kelsey Kaeding, Rotation Student
2c Katherine Palozola, Graduate Student
2b Naomi Takenaka, Research Specialist
2f Ann O'Brien Jenkins, Research Specialist
26 29
23
eb Becker Justin S, Nicetto Dario, Zaret Kenneth S: H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes. Trends in genetics : TIG 32(1): 29-41, Jan 2016.
116 Bhat Neha, Park Jeehye, Zoghbi Huda Y, Arthur J Simon C, Zaret Kenneth S: The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development. PloS one 11(12): e0166703, 2016.
137 Soufi Abdenour, Garcia Meilin Fernandez, Jaroszewicz Artur, Osman Nebiyu, Pellegrini Matteo, Zaret Kenneth S: Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161(3): 555-68, Apr 2015.
e6 Kim Jungsun, Zaret Kenneth S: Reprogramming of human cancer cells to pluripotency for models of cancer progression. The EMBO journal 34(6): 739-47, Mar 2015.
d2 Iwafuchi-Doi Makiko, Zaret Kenneth S: Pioneer transcription factors in cell reprogramming. Genes & development 28(24): 2679-92, Dec 2014.
133 Xu Cheng-Ran, Li Lin-Chen, Donahue Greg, Ying Lei, Zhang Yu-Wei, Gadue Paul, Zaret Kenneth S: Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification. The EMBO journal 33(19): 2157-70, Oct 2014.
112 Xu,C.R., Li, L.C., Donahue, G., Ying, L., Zhang, Y.W., Gadue, P., Zaret, K.S.: Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification. EMBO Journal August 2014.
f4 Bhatia Sangeeta N, Underhill Gregory H, Zaret Kenneth S, Fox Ira J: Cell and tissue engineering for liver disease. Science translational medicine 6(245): 245sr2, Jul 2014.
10d Metzger, D.E., Liu, C., Ziaie, A.S., Naji, A., Zaret, K.S.: Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic β-cells while repressing α-cell functions. Diabetes 63(5): 1804-1816, May 2014.
2c
7
1d
1f
Selected Publications
188 Iwafuchi-Doi Makiko, Donahue Greg, Kakumanu Akshay, Watts Jason A, Mahony Shaun, Pugh B Franklin, Lee Dolim, Kaestner Klaus H, Zaret Kenneth S: The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation. Molecular cell 62(1): 79-91, Apr 2016.eb Becker Justin S, Nicetto Dario, Zaret Kenneth S: H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes. Trends in genetics : TIG 32(1): 29-41, Jan 2016.
116 Bhat Neha, Park Jeehye, Zoghbi Huda Y, Arthur J Simon C, Zaret Kenneth S: The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development. PloS one 11(12): e0166703, 2016.
137 Soufi Abdenour, Garcia Meilin Fernandez, Jaroszewicz Artur, Osman Nebiyu, Pellegrini Matteo, Zaret Kenneth S: Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161(3): 555-68, Apr 2015.
e6 Kim Jungsun, Zaret Kenneth S: Reprogramming of human cancer cells to pluripotency for models of cancer progression. The EMBO journal 34(6): 739-47, Mar 2015.
d2 Iwafuchi-Doi Makiko, Zaret Kenneth S: Pioneer transcription factors in cell reprogramming. Genes & development 28(24): 2679-92, Dec 2014.
133 Xu Cheng-Ran, Li Lin-Chen, Donahue Greg, Ying Lei, Zhang Yu-Wei, Gadue Paul, Zaret Kenneth S: Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification. The EMBO journal 33(19): 2157-70, Oct 2014.
112 Xu,C.R., Li, L.C., Donahue, G., Ying, L., Zhang, Y.W., Gadue, P., Zaret, K.S.: Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification. EMBO Journal August 2014.
f4 Bhatia Sangeeta N, Underhill Gregory H, Zaret Kenneth S, Fox Ira J: Cell and tissue engineering for liver disease. Science translational medicine 6(245): 245sr2, Jul 2014.
10d Metzger, D.E., Liu, C., Ziaie, A.S., Naji, A., Zaret, K.S.: Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic β-cells while repressing α-cell functions. Diabetes 63(5): 1804-1816, May 2014.
2c