Children's Hospital of Philadelphia 3615 Civic Center Blvd. CTRB, Rm. 5012

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.

Rotation Projects
Please contact Dr. Gadue for rotation projects.

Lab Personnel
Lei Ying, Research Associate
Amita Tiyaboonchai, Graduate Student
Siddharth Kishore, Research Technician
Chiamin Liao, Postdoctoral Fellow
Xiuli Sim, Graduate Student
Fabian Cardenas, Graduate Student
Hridey Manghwani, Research Technician

Human ES/iPS cell core facility*
Floris Van Alphen, Research Technician
Jason Mills, Research Associate
Prasuna Paluru, Research Associate
Helen Mac, Research Technician
Chintan Jobaliya, Research Technician

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

Assistant Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (2008– present)
Ph.D., Immunology, University of Pennsylvania, Philadelphia, PA (2002)
B.S, Cell and Developmental Biology, University of Rochester, Rochester NY (1995)
Selected Publications
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. 2013 Aug.
Garçon Loïc, Ge Jingping, Manjunath Shwetha H, Mills Jason A, Apicella Marisa, Parikh Shefali, Sullivan Lisa M, Podsakoff Gregory M, Gadue Paul, French Deborah L, Mason Philip J, Bessler Monica, Weiss Mitchell J. Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.. Blood. 2013 Jun.
Smith Brenden W, Rozelle Sarah S, Leung Amy, Ubellacker Jessalyn, Parks Ashley, Nah Shirley K, French Deborah, Gadue Paul, Monti Stefano, Chui David H K, Steinberg Martin H, Frelinger Andrew L, Michelson Alan D, Theberge Roger, McComb Mark E, Costello Catherine E, Kotton Darrell N, Mostoslavsky Gustavo, Sherr David H, Murphy George J. The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation.. Blood. 2013 May.
Cheng Xin, Tiyaboonchai Amita, Gadue Paul. Endodermal stem cell populations derived from pluripotent stem cells.. Current opinion in cell biology. Vol 25(2) . 2013 Apr:265-71.
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. Vol 151(7) . 2012 Dec 21:1608-16.
Chou Stella T, Byrska-Bishop Marta, Tober Joanna M, Yao Yu, Vandorn Daniel, Opalinska Joanna B, Mills Jason A, Choi John Kim, Speck Nancy A, Gadue Paul, Hardison Ross C, Nemiroff Richard L, French Deborah L, Weiss Mitchell J. Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells.. Proceedings of the National Academy of Sciences of the United States of America. Vol 109(43) . 2012 Oct:17573-8.