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
Xin Cheng, Posdoctoral Fellow
Lei Ying, Research Associate
Amita Tiyaboonchai, Graduate Student
Siddharth Kishore, Research Technician
Chiamin Liao, Postdoctoral Fellow
Xiuli Sim, Graduate Student
Fabian Cardenas, Graduate Student
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
Selected Publications
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 Jun 2013.
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 May 2013.
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.
Vasireddy Vidyullatha, Mills Jason A, Gaddameedi Rajashekhar, Basner-Tschakarjan Etiena, Kohnke Monika, Black Aaron D, Alexandrov Krill, Zhou Shangzhen, Maguire Albert M, Chung Daniel C, Mac Helen, Sullivan Lisa, Gadue Paul, Bennicelli Jeannette L, French Deborah L, Bennett Jean: AAV-mediated gene therapy for choroideremia: preclinical studies in personalized models. PloS one 8(5): e61396, 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, Jyh-Chang Jean, 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.
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.
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 109(43): 17573-8, Oct 2012.
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.
Sommer Andreia Gianotti, Rozelle Sarah S, Sullivan Spencer, Mills Jason A, Park Seon-Mi, Smith Brenden W, Iyer Amulya M, French Deborah L, Kotton Darrell N, Gadue Paul, Murphy George J, Mostoslavsky Gustavo: Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Using the STEMCCA Lentiviral Vector. Journal of visualized experiments : JoVE(68), 2012.
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Last updated: 08/02/2013
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