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
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. Lastly, we are also using the stem cell system to model genetic forms of diabetes.
Please contact Dr. Gadue for rotation projects.
Lei Ying, Research Associate
Amita Tiyaboonchai, Graduate Student
Siddharth Kishore, Research Technician
Chiamin Liao, Postdoctoral Fellow
Xiuli Sim, Graduate Student
Fabian Cardenas, Graduate Student
Somdutta Mukherjee, 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
Noh Ji-Yoon, Gandre-Babbe Shilpa, Wang Yuhuan, Hayes Vincent, Yao Yu, Gadue Paul, Sullivan Spencer K, Chou Stella T, Machlus Kellie R, Italiano Joseph E, Kyba Michael, Finkelstein David, Ulirsch Jacob C, Sankaran Vijay G, French Deborah L, Poncz Mortimer, Weiss Mitchell J: Inducible Gata1 suppression expands megakaryocyte-erythroid progenitors from embryonic stem cells. The Journal of clinical investigation May 2015.
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.
Byrska-Bishop Marta, VanDorn Daniel, Campbell Amy E, Betensky Marisol, Arca Philip R, Yao Yu, Gadue Paul, Costa Fernando F, Nemiroff Richard L, Blobel Gerd A, French Deborah L, Hardison Ross C, Weiss Mitchell J, Chou Stella T: Pluripotent stem cells reveal erythroid-specific activities of the GATA1 N-terminus. The Journal of clinical investigation Jan 2015.
Ditadi Andrea, Sturgeon Christopher, Tober Joanna, Awong Geneve, Kennedy Marion, Phillips Amanda, Azzola Lisa, Ng Elizabeth, Stanley Edouard, French Deborah, Cheng Xin, Gadue Paul, Speck Nancy, Elefanty Andrew, and Keller Gordon: Haemogenic endothelium and arterial vascular endothelium represent
distinct lineages. Nature cell biology in press, 2015.
Wilson Andrew A, Ying Lie, Liesa Marc, Segeritz Charis-P, Mills Jason A, Shen Steven S, Jean Jyh C, Lonza Geordie C, Nazaire Jean, Shiriai Orian, Murphy George J, Mostoslavsky Gustavo, Gower Adam, Spira Avrum, Vallier Ludovic, Ramirez Marisa, Gadue Paul*, Kotton Darrell N*: Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells. Stem Cell Reports in press, 2015 Notes: *co-corresponding authors.
Wang Yuhuan, Hayes Vincent, Jarocha Danuta J, Sim Xiuli, Dawn C Harper, Fuentes Rudy, Sullivan Spencer K, Gadue Paul, Chou Stella T, Torok-Storb Beverly, Marks Michael S, French Deborah L, Poncz Mortimer: Comparative analysis of human ex vivo-generatedplatelets vs. megakaryocyte-generated platelets in mice: A cautionary tale. Blood in press, 2015.
Xu Cheng-Ran, Li Lin-Chen, Donahue Greg, Ying Lei, Zhang Yu-Wei, Gadue Paul, Zaret Kenneth S: Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification. The EMBO journal 33: 2157-2170, Aug 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.
Kamat Viraj, Paluru Prasuna, Myint Melissa, French Deborah L, Gadue Paul, Diamond Scott L: MicroRNA screen of human embryonic stem cell differentiation reveals miR-105 as an enhancer of megakaryopoiesis from adult CD34+ cells. Stem cells (Dayton, Ohio) 32(5): 1337-1346, Jan 2014.
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.
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Last updated: 05/15/2015
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