PEOPLE

Paul J. Gadue, PhD

Associate Professor of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine

Contact InformationChildren's Hospital of Philadelphia
3615 Civic Center Blvd.
CTRB, Rm. 5012
Philadelphia, PA 19104
Office: 267-426-9607

Email: gaduep@email.chop.edu

Specialty Division

Immunobiology and Experimental Pathology

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 as well as using CRISPR/Cas9 technology to both correct mutant iPS cell lines and generate patient specific mutations in wild-type lines.

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 human stem cell model to study pancreatic beta cell specification with the goal of generating functional beta cells from human ES and iPS cells. Lastly, we are using the stem cell system to model genetic forms of diabetes, using both patient specific iPS cells and genome editing to generate genetic models of these diseases.

Rotation Projects
Please contact Dr. Gadue for rotation projects.


Lab Personnel
Lei Ying, Research Associate
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

Graduate Groups

Cell and Molecular Biology

Education

B.S (Cell and Developmental Biology), University of Rochester, Rochester NY, 1995
Ph.D. (Immunology), University of Pennsylvania, Philadelphia, PA, 2002

Specialty Certification

Postgraduate Training

Post Doctoral Fellow, Laboratory of Dr. Gordon Keller, Mt. Sinai School of Medicine, New York, NY, 2002-2008
Post Doctoral Fellow, University of Pennsylvania, Philadelphia, PA., 2002-2002

Awards and Honors

Predoctoral fellowship, NIH training grant: Immunology of the Eye., 1995-2000
Goldie Simon Preceptorship Award, Lupus Foundation of Southeastern Pennsylvania., 2002
Ruth L. Kirschstein National Research Service Award, NIH., 2003-2006

Memberships and Professional Organizations

International Society for Stem Cell Research, 2004 - Present
NIH, 2009 - 2009
Society for Hematology and Stem Cells, 2010 - Present
American Society of Gene and Cell Therapy, 2011 - Present
American Diabetes Association, 2013 - Present

Web Links


Selected Publications

Identifying and enriching the platelet-producing human stem cell-derived megakaryocytes using factor V uptake.

Sim Xiuli, Jarocha Danuta, Hayes Vincent, Hanby Hayley A, Marks Michael S, Camire Rodney M, French Deborah L, Poncz Mortimer, Gadue Paul, Blood, 2017, PMID:28455282

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GATA6 Plays an Important Role in the Induction of Human Definitive Endoderm, Development of the Pancreas, and Functionality of Pancreatic β Cells.

Tiyaboonchai Amita, Cardenas-Diaz Fabian L, Ying Lei, Maguire Jean Ann, Sim Xiuli, Jobaliya Chintan, Gagne Alyssa L, Kishore Siddharth, Stanescu Diana E, Hughes Nkecha, De Leon Diva D, French Deborah L, Gadue Paul, Stem cell reports, 2017, PMID:28196690

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Generation of human control iPS cell line CHOPWT10 from healthy adult peripheral blood mononuclear cells.

Maguire Jean Ann, Gagne Alyssa L, Jobaliya Chintan D, Gandre-Babbe Shilpa, Gadue Paul, French Deborah L, Stem cell research 16(2): 338-41, 2016, PMID:27345999

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Generation of Hermansky-Pudlak Syndrome Type 1 (HPS1) induced pluripotent stem cells (iPSCs).

Maguire Jean Ann, Lu Lin, Mills Jason A, Sullivan Lisa M, Gagne Alyssa, Gadue Paul, French Deborah L, Stem cell research 16(2): 233-5, 2016, PMID:27345974

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Generation of Hermansky Pudlak syndrome type 2 (HPS2) induced pluripotent stem cells (iPSCs).

Maguire Jean Ann, Lu Lin, Mills Jason A, Sullivan Lisa M, Gadue Paul, French Deborah L, Stem cell research 16(2): 287-9, 2016, PMID:27345985

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Generation of human control iPS cell line CHOPWT9 from healthy adult peripheral blood mononuclear cells.

Maguire Jean Ann, Gagne Alyssa, Mills Jason A, Gadue Paul, French Deborah L, Stem cell research 16(1): 14-6, 2016, PMID:27345777

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Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets.

Sim Xiuli, Poncz Mortimer, Gadue Paul, French Deborah L, Blood, 2016, PMID:26787738

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Factors Regulating Stem Cell Biology in Development and Disease.

Liebau Stefan, Gadue Paul, Nalapareddy Kodandaramireddy, von Figura Guido, Kleger Alexander, Stem cells international 2016(): 7170642, 2016, PMID:26798362

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OCT4 Coordinates with WNT Signaling to Pre-pattern Chromatin at the SOX17 Locus during Human ES Cell Differentiation into Definitive Endoderm.

Ying Lei, Mills Jason A, French Deborah L, Gadue Paul, Stem cell reports 5(4): 490-8, 2015, PMID:26411902

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Comparative analysis of human ex vivo-generated platelets vs megakaryocyte-generated platelets in mice: a cautionary tale.

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, Blood 125(23): 3627-36, 2015, PMID:25852052

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