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
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 human development, 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
Mathew George, Postdoctoral Fellow
Catriana Nations, Graduate Student
Somdutta Mukherjee, Graduate Student
Sara Borst, Graduate Student
Karla Leavens, Endocrinology Attending Physician
Giulia Pavani, Research Associate

Human ES/iPS cell core facility*
Jean Ann Maguire, Stem Cell Core Technical Director
Alyssa Gagne, Research Technician
Chintan Jobaliya, Laboratory Manager
Elisa Waxman, Research Associate


* Dr. Gadue is Associate Director of the CHOP human ES/iPS cell core facility

Selected Publications

Kishore Siddharth, De Franco Elisa, Cardenas-Diaz Fabian L, Letourneau-Freiberg Lisa R, Sanyoura May, Osorio-Quintero Catherine, French Deborah L, Greeley Siri Atma W, Hattersley Andrew T, Gadue Paul: A Non-Coding Disease Modifier of Pancreatic Agenesis Identified by Genetic Correction in a Patient-Derived iPSC Line. Cell stem cell 27: 1-10, August 2020.

Lorberbaum David S, Kishore Siddharth , Rosselot Carolina , Sarbaugh Dylan , Brooks Elliott P, Aragon Eloise , Xuan Shouhong, Simon Olivier , Ghosh Debashis, Mendelsohn Cathy, Gadue Paul, Sussel Lori: Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification. Development EPub, 2020.

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.

Cardenas-Diaz Fabian L, Maguire Jean Ann, Gadue Paul*, French Deborah L*: Generation of Defined Genomic Modifications Using CRISPR-CAS9 in Human Pluripotent Stem Cells. Journal of visualized experiments : JoVE(151), Sep 2019 Notes: * co-corresponding author.

Chen Yi-Ju, Yamazoe Taiji, Leavens Karla F, Cardenas-Diaz Fabian L, Georgescu Andrei, Huh Dongeun, Gadue Paul, Stanger Ben Z: iPreP is a three-dimensional nanofibrillar cellulose hydrogel platform for long-term ex vivo preservation of human islets. JCI insight 4(21), Nov 2019.

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.

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.

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 8(3): 589-604, Feb 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.

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.

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.

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.

Sullivan Spencer K, Mills Jason A, Koukouritaki Sevasti B, Vo Karen K, Lyde Randolph B, Paluru Prasuna, Zhao Guoha, Zhai Li, Sullivan Lisa M, Wang Yuhuan, Kishore Siddharth, Gharaibeh Eyad Z, Lambert Michele P, Wilcox David A, French Deborah L, Poncz Mortimer, Gadue Paul: High-level transgene expression in induced pluripotent stem cell-derived megakaryocytes: correction of Glanzmann thrombasthenia. Blood 123(5): 753-7, Jan 2014.

Tiyaboonchai Amita, Mac Helen, Shamsedeen Razveen, Mills Jason A, Kishore Siddarth, French Deborah L, Gadue Paul: Utilization of the AAVS1 safe harbor locus for hematopoietic specific transgene expression and gene knockdown in human ES cells. Stem cell research 12(3): 630-637, Feb 2014.

Cheng Xin, Tiyaboonchai Amita, Gadue Paul: Endodermal stem cell populations derived from pluripotent stem cells. Current opinion in cell biology 25(2): 265-71, Apr 2013.

Mills Jason A, Wang Kai, Paluru Prasuna, Ying Lei, Lu Lin, Galvão Aline M, Xu Dongbin, Yao Yu, Sullivan Spencer K, Sullivan Lisa M, Mac Helen, Omari Amel, Jean Jyh-Chang, Shen Steve, Gower Adam, Spira Avi, Mostoslavsky Gustavo, Kotton Darrell N, French Deborah L, Weiss Mitchell J, Gadue Paul: Clonal genetic and hematopoietic heterogeneity among human induced pluripotent stem cell lines. Blood 122(12): 2047-51, Aug 2013.

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.

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 151(7): 1608-16, Dec 21 2012.

Nostro M Cristina, Cheng Xin, Keller Gordon M, Gadue Paul: Wnt, activin, and BMP signaling regulate distinct stages in the developmental pathway from embryonic stem cells to blood. Cell stem cell 2(1): 60-71, Jan 2008.

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Last updated: 03/26/2021
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