Research Interest
My laboratory studies cell fate decisions, focusing on endoderm and mesoderm specification using mouse and human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells.
Key Words: Stem Cell Research, ES cells, Megakaryocyte, Developmental Biology, ES Cell Differentiation, Mesoderm, Endoderm, iPS cells, Pancreas, Beta cell
Research Details
My laboratory studies cell fate decisions, focusing on endoderm and mesoderm specification using mouse and human ES cells and iPS cells. ES/iPS cells can differentiate into all cell types in the body and can be propagated in culture almost indefinitely, generating a virtually unlimited number of cells. These unique characteristics lead to the exciting prospect of using these cells to study disease processes and developmental pathways in vitro and eventually to treat a wide variety of diseases using cell replacement therapies.
The differentiation of ES cells into a given cell type closely mimics how that cell type is formed during embryogenesis. This developmental pathway starts with the formation of the primary germ layers, mesoderm, endoderm, and ectoderm. Progressively more differentiated cell types are formed until the functional mature cell is generated. My research program focuses on understanding the molecular mechanisms that regulate endoderm and mesoderm development utilizing the in vitro differentiation of ES cells and iPS cells.
One area of interest in the lab is in investigating hematopoiesis with a focus on megakaryocyte development. We are studying the molecular pathways which regulate megakaryopoeisis with the goal of optimizing the generation of platelets in vitro from ES/iPS cells. In addition, we are developing in vitro models of platelet disorders using iPS cells derived from patients with genetic diseases affecting platelet development and function.
The second area of interest in the lab is endoderm formation. We are studying a unique endodermal stem cell population that we have generated from human ES and iPS cells. Endoderm stem cells have the ability to be expanded in culture like ES cells and have the capability to generate many endoderm derived tissues such as liver, pancreas and intestine. We are studying the signaling and transcriptional pathways which regulate endoderm stem cell generation and maintenance. We are also utilizing the endodermal stem cell population as a model to study pancreatic beta cell specification with the goal of generating functional beta cells from human ES and iPS cells.
Rotation Projects
Please contact Dr. Gadue for rotation projects.
Lab Personnel
Xin Cheng, Posdoctoral Fellow
Lei Ying, Research Associate
Amita Tiyaboonchai, Graduate Student
Siddharth Kishore, Research Technician
Chiamin Liao, Postdoctoral Fellow
Xiuli Sim, Graduate Student
Spencer Sullivan, Fellow
Human ES/iPS cell core facility*
Aline Disimone, Lab Manager
Jason Mills, Research Associate
Prasuna Paluru, Research Associate
Helen Mac, Research Technician
Chintan Jobaliya, Research Technician
* Dr. Gadue is associate director of the CHOP human ES/iPS cell core facility
Selected Publications
Chou Stella T, Byrska-Bishop Marta, Tober Joanna M, Yao Yu, Vandorn Daniel, Opalinska Joanna B, Mills Jason A, Choi John Kim, Speck Nancy A, Gadue Paul, Hardison Ross C, Nemiroff Richard L, French Deborah L, Weiss Mitchell J: Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells. Proceedings of the National Academy of Sciences of the United States of America 109(43): 17573-8, Oct 2012.
Cheng Xin, Ying Lei, Lu Lin, Galvão Aline M, Mills Jason A, Lin Henry C, Kotton Darrell N, Shen Steven S, Nostro M Cristina, Choi John Kim, Weiss Mitchell J, French Deborah L, Gadue Paul: Self-renewing endodermal progenitor lines generated from human pluripotent stem cells. Cell stem cell 10(4): 371-84, Apr 2012.
Outten Joel T, Gadue Paul, French Deborah L, Diamond Scott L: High-throughput screening assay for embryoid body differentiation of human embryonic stem cells. Current protocols in stem cell biology Chapter 1: Unit 1D.6, Mar 2012.
Sommer Andreia Gianotti, Rozelle Sarah S, Sullivan Spencer, Mills Jason A, Park Seon-Mi, Smith Brenden W, Iyer Amulya M, French Deborah L, Kotton Darrell N, Gadue Paul, Murphy George J, Mostoslavsky Gustavo: Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Using the STEMCCA Lentiviral Vector. Journal of visualized experiments : JoVE(68), 2012.
Li Zhaoyu, Gadue Paul, Chen Kaifu, Jiao Yang, Tuteja Geetu, Schug Jonathan, Li Wei, Kaestner Klaus H: Foxa2 and H2A.Z Mediate Nucleosome Depletion during Embryonic Stem Cell Differentiation. Cell accepted, 2012.
Christodoulou Constantina, Longmire Tyler A, Shen Steven S, Bourdon Alice, Sommer Cesar A, Gadue Paul, Spira Avrum, Gouon-Evans Valerie, Murphy George J, Mostoslavsky Gustavo, Kotton Darrell N: Mouse ES and iPS cells can form similar definitive endoderm despite differences in imprinted genes. The Journal of clinical investigation 121(6): 2313-25, Jun 2011.
Outten Joel T, Cheng Xin, Gadue Paul, French Deborah L, Diamond Scott L: A high-throughput multiplexed screening assay for optimizing serum-free differentiation protocols of human embryonic stem cells. Stem cell research 6(2): 129-42, Mar 2011.
Han Songyan, Dziedzic Noelle, Gadue Paul, Keller Gordon M, Gouon-Evans Valerie: An endothelial cell niche induces hepatic specification through dual repression of Wnt and Notch signaling. Stem cells (Dayton, Ohio) 29(2): 217-28, Feb 2011.
Cheng Xin, Gadue Paul: Liver regeneration from induced pluripotent stem cells. Molecular therapy : the journal of the American Society of Gene Therapy 18(12): 2044-5, Dec 2010.
Somers Aba, Jean Jyh-Chang, Sommer Cesar A, Omari Amel, Ford Christopher C, Mills Jason A, Ying Lei, Sommer Andreia Gianotti, Jean Jenny M, Smith Brenden W, Lafyatis Robert, Demierre Marie-France, Weiss Daniel J, French Deborah L, Gadue Paul, Murphy George J, Mostoslavsky Gustavo, Kotton Darrell N: Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette. Stem cells (Dayton, Ohio) 28(10): 1728-40, Oct 2010.
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Last updated: 09/27/2012
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