Paul J Gadue, PhD

faculty photo
Associate 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
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 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 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 supply 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 a 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 using the human stem cell model to study endoderm patterning examining pancreas, liver and lung specification and transcriptional control of these fate decisions. We also have a focus on 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
Catherine Osorio Quintero, Research Technician
Chiamin Liao, Research Associate
Siddharth Kishore, Graduate Student
Fabian Cardenas, Graduate Student
Somdutta Mukherjee, Graduate Student
Sara Borst, Graduate Student
Karla Leavens, Endocrinology Fellow

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

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

Selected Publications

Cardenas-Diaz Fabian L, Osorio-Quintero Catherine, Diaz-Miranda Maria A, Kishore Siddharth, Leavens Karla, Jobaliya Chintan, Stanescu Diana, Ortiz-Gonzalez Xilma, Yoon Christine, Chen Christopher S, Haliyur Rachana, Brissova Marcela, Powers Alvin C, French Deborah L, Gadue Paul: Modeling Monogenic Diabetes using Human ESCs Reveals Developmental and Metabolic Deficiencies Caused by Mutations in HNF1A. Cell stem cell 25(2): 273-289.e5, Aug 2019.

Maguire Jean Ann, Gagne Alyssa L, Gonzalez-Alegre Pedro, Davidson Beverly L, Shakkottai Vikram, Gadue Paul, French Deborah L: Generation of Spinocerebellar Ataxia Type 2 induced pluripotent stem cell lines, CHOPi002-A and CHOPi003-A, from patients with abnormal CAG repeats in the coding region of the ATXN2 gene. Stem cell research 34: 101361, Dec 2018.

Maguire Jean Ann, Cardenas-Diaz Fabian L, Gadue Paul*, French Deborah L*: Highly Efficient CRISPR-Cas9-Mediated Genome Editing in Human Pluripotent Stem Cells. Current protocols in stem cell biology Page: e64, Oct 2018 Notes: * co-corresponding author.

Gagne Alyssa L, Maguire Jean Ann, Gandre-Babbe Shilpa, Chou Stella T, Tasian Sarah K, Loh Mignon L, Weiss Mitchell J, Gadue Paul, French Deborah L: Generation of a human Juvenile myelomonocytic leukemia iPSC line, CHOPi001-A, with a mutation in CBL. Stem cell research 31: 157-160, Jul 2018.

Liao Chia-Min, Mukherjee Somdutta, Tiyaboonchai Amita, Maguire Jean Ann, Cardenas-Diaz Fabian L, French Deborah L, Gadue Paul: GATA6 suppression enhances lung specification from human pluripotent stem cells. The Journal of clinical investigation 128(7): 2944-2950, Jun 2018.

Beauvais Genevieve, Rodriguez-Losada Noela, Ying Lei, Zakirova Zuchra, Watson Jaime L, Readhead Ben, Gadue Paul, French Deborah L, Ehrlich Michelle E, Gonzalez-Alegre Pedro: Exploring the Interaction Between eIF2α Dysregulation, Acute Endoplasmic Reticulum Stress and DYT1 Dystonia in the Mammalian Brain. Neuroscience 371: 455-468, Dec 2017.

Borst Sara, Sim Xiuli, Poncz Mortimer, French Deborah L, Gadue Paul: Induced Pluripotent Stem Cell-Derived Megakaryocytes and Platelets for Disease Modeling and Future Clinical Applications. Arteriosclerosis, thrombosis, and vascular biology 37(11): 2007-2013, Nov 2017.

Sim Xiuli, Jarocha Danuta, Hayes Vincent, Hanby Hayley A, Marks Michael S, Camire Rodney M, French Deborah L, Poncz Mortimer, Gadue Paul: Identifying and enriching the platelet-producing human stem cell-derived megakaryocytes using factor V uptake. Blood 130(2): 192-204, Apr 2017.

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: GATA6 Plays an Important Role in the Induction of Human Definitive Endoderm, Development of the Pancreas, and Functionality of Pancreatic β Cells. Stem cell reports Feb 2017.

Maguire Jean Ann, Gagne Alyssa L, Jobaliya Chintan D, Gandre-Babbe Shilpa, Gadue Paul, French Deborah L: Generation of human control iPS cell line CHOPWT10 from healthy adult peripheral blood mononuclear cells. Stem cell research 16(2): 338-41, Mar 2016.

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Last updated: 08/19/2019
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