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.
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
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
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 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) 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.
Mills Jason A, Paluru Prasuna, Weiss Mitchell J, Gadue Paul, French Deborah L: Hematopoietic differentiation of pluripotent stem cells in culture. Methods in molecular biology (Clifton, N.J.) 1185: 181-94, 2014.
Paluru Prasuna, Hudock Kristin M, Cheng Xin, Mills Jason A, Ying Lei, Galvão Aline M, Lu Lin, Tiyaboonchai Amita, Sim Xiuli, Sullivan Spencer K, French Deborah L, Gadue Paul: The negative impact of Wnt signaling on megakaryocyte and primitive erythroid progenitors derived from human embryonic stem cells. Stem cell research 12(2): 441-451, Dec 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.
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 122(6): 912-21, Jun 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, May 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 122(3): 376-85, May 2013.
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Last updated: 09/09/2014
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