Paul J Gadue, PhD

faculty photo
Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
3615 Civic Center Blvd.
CTRB, Rm. 5012
Philadelphia, PA 19104
Office: 267-426-9607
Education:
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, Liver, 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 and liver specification with the goal of generating functional beta cells and hepatocytes 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
Spencer Sullivan, Fellow

Human ES/iPS cell core facility*
Aline Disimone, Lab Manager
Jason Mills, Posdoctoral Fellow
Prasuna Paluru, Research Associate
Lin Lu, Research Associate
Helen Mac, Research Technician

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

Selected Publications

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.

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.

Xu Jian, Watts Jason A, Pope Scott D, Gadue Paul, Kamps Mark, Plath Kathrin, Zaret Kenneth S, Smale Stephen T: Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cells. Genes & development 23(24): 2824-38, Dec 2009.

Gadue Paul, Gouon-Evans Valerie, Cheng Xin, Wandzioch Ewa, Zaret Kenneth S, Grompe Markus, Streeter Philip R, Keller Gordon M: Generation of monoclonal antibodies specific for cell surface molecules expressed on early mouse endoderm. Stem cells (Dayton, Ohio) 27(9): 2103-13, Sep 2009.

Gadue Paul, Weiss Mitchell J: Stem cells unscramble yolk sac hematopoiesis. Blood 114(8): 1455-6, Aug 2009.

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Last updated: 05/15/2012
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