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Paul J Gadue

Associate Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine

Contact information
Children's Hospital of Philadelphia
3615 Civic Center Blvd.
CTRB, Rm. 5012
Philadelphia, PA 19104
Office: 267-426-9607
Graduate Group Affiliations
B.S (Cell and Developmental Biology)
University of Rochester, Rochester NY, 1995.
Ph.D. (Immunology)
University of Pennsylvania, Philadelphia, PA, 2002.
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Description of Research Expertise

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. Lastly, we are also using the stem cell system to model genetic forms of diabetes.

Rotation Projects
Please contact Dr. Gadue for rotation projects.

Lab Personnel
Lei Ying, Research Associate
Amita Tiyaboonchai, Graduate Student
Siddharth Kishore, Graduate Student
Chiamin Liao, Postdoctoral Fellow
Xiuli Sim, Graduate Student
Fabian Cardenas, Graduate Student
Somdutta Mukherjee, Graduate Student
Sara Borst, Graduate Student

Human ES/iPS cell core facility*
Jean Ann Maguire, Research Associate
Alyssa Gagne, Research Technician
Chintan Jobaliya, Research Technician
Grace Liang, Research Associate

* Dr. Gadue is associate director of the CHOP human ES/iPS cell core facility

Selected Publications

Sim Xiuli, Poncz Mortimer, Gadue Paul, French Deborah L: Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets. Blood Jan 2016.

Liebau Stefan, Gadue Paul, Nalapareddy Kodandaramireddy, von Figura Guido, Kleger Alexander: Factors Regulating Stem Cell Biology in Development and Disease. Stem cells international 2016: 7170642, 2016.

Ying Lei, Mills Jason A, French Deborah L, Gadue Paul: OCT4 Coordinates with WNT Signaling to Pre-pattern Chromatin at the SOX17 Locus during Human ES Cell Differentiation into Definitive Endoderm. Stem cell reports 5(4): 490-8, Oct 2015.

Wang Yuhuan, Hayes Vincent, Jarocha Danuta, Sim Xiuli, Harper Dawn C, Fuentes Rudy, Sullivan Spencer K, Gadue Paul, Chou Stella T, Torok-Storb Beverly J, Marks Michael S, French Deborah L, Poncz Mortimer: Comparative analysis of human ex vivo-generated platelets vs megakaryocyte-generated platelets in mice: a cautionary tale. Blood 125(23): 3627-36, Jun 2015.

Wilson Andrew A, Ying Lei, Liesa Marc, Segeritz Charis-Patricia, Mills Jason A, Shen Steven S, Jean Jyhchang, Lonza Geordie C, Liberti Derek C, Lang Alex H, Nazaire Jean, Gower Adam C, Müeller Franz-Josef, Mehta Pankaj, Ordóñez Adriana, Lomas David A, Vallier Ludovic, Murphy George J, Mostoslavsky Gustavo, Spira Avrum, Shirihai Orian S, Ramirez Maria I, Gadue Paul*, Kotton Darrell N*: Emergence of a stage-dependent human liver disease signature with directed differentiation of alpha-1 antitrypsin-deficient iPS cells. Stem cell reports 4(5): 873-85, May 2015 Notes: * Co-corresponding author.

Ditadi Andrea, Sturgeon Christopher M, Tober Joanna, Awong Geneve, Kennedy Marion, Yzaguirre Amanda D, Azzola Lisa, Ng Elizabeth S, Stanley Edouard G, French Deborah L, Cheng Xin, Gadue Paul, Speck Nancy A, Elefanty Andrew G, Keller Gordon: Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages. Nature cell biology 17(5): 580-91, May 2015.

Noh Ji-Yoon, Gandre-Babbe Shilpa, Wang Yuhuan, Hayes Vincent, Yao Yu, Gadue Paul, Sullivan Spencer K, Chou Stella T, Machlus Kellie R, Italiano Joseph E, Kyba Michael, Finkelstein David, Ulirsch Jacob C, Sankaran Vijay G, French Deborah L, Poncz Mortimer, Weiss Mitchell J: Inducible Gata1 suppression expands megakaryocyte-erythroid progenitors from embryonic stem cells. The Journal of clinical investigation 125(6): 2369-74, May 2015.

Sim Xiuli, Cardenas-Diaz Fabian L, French Deborah L, Gadue Paul: A Doxycycline-Inducible System for Genetic Correction of iPSC Disease Models. Methods in molecular biology (Clifton, N.J.) Jan 2015.

Byrska-Bishop Marta, VanDorn Daniel, Campbell Amy E, Betensky Marisol, Arca Philip R, Yao Yu, Gadue Paul, Costa Fernando F, Nemiroff Richard L, Blobel Gerd A, French Deborah L, Hardison Ross C, Weiss Mitchell J, Chou Stella T: Pluripotent stem cells reveal erythroid-specific activities of the GATA1 N-terminus. The Journal of clinical investigation Jan 2015.

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: 2157-2170, Aug 2014.

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Last updated: 03/01/2016
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