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Peggi Angel, PhD
Training focus:Heart valve proteome during organ development in vitro
Training period:06/23/2008 – 06/22/2010Co-mentors:Scott Baldwin, MD Richard Caprioli, PhD
Abnormal heart valve formation affects over 1% of the US population and is a primary cause of prenatal and postnatal death. Although morphological progression of heart valve development has been well studied, the molecular factors that guide this process are poorly defined. Our goal is to produce a comprehensive proteomic portrait of early mouse heart valve development. A key element of this goal is the identification of proteins important to endothelial-mesenchymal transformation, a process that is critical not only to early valve cushion formation but to other major developmental events such as tooth germ formation. The data will be made available for comparison to tooth germ formation and pancreatic islet formation to better understand the developmentally important endothelial-mesenchymal transformation. Information from this study will be directly applicable to tissue engineering approaches to heart valve formation. |
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Otger Campàs, PhD
Training focus:Mechanical determinants of tooth formation
Training period:06/01/2009 – 05/31/2011Co-mentors:Donald Ingber, MD, PhD Lakshminarayanan Mahadevan, PhD
The ultimate functional morphology of a tissue is governed by both signaling molecules and physical forces. Understanding how mechanics and gene expression act together to shape tissues would be of capital importance to design ways in which developmental processes could be guided to engineer organ morphology. In order to address these questions we will focus on tooth formation because the signaling molecules that orchestrate the different stages of development are relatively well known and also because it is simple enough for theoretical treatment. As a SysCODE fellow I will approach tooth development from two different, but complementary, perspectives: |
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Kaustabh Ghosh, PhD
Training focus:Engineered microenvironments for in situ pancreatic islet generation
Training period:06/30/2008 – 06/29/2010Co-mentors:Donald Ingber, MD, PhD Robert S. Langer, PhD
Diabetes, which poses major health and financial burden, arises from the loss of insulin production by ß cells of the islets of Langerhans. Islet transplantation, however, has had limited success in restoring normal islet function, largely due to post-transplantation challenges such as immune rejection, loss of islet cell viability and lack of optimal vascularization, thus suggesting the need to develop alternate therapies. For this proposal, I will seek to identify micro-environmental (chemical as well as physical) determinants that promote EPC adhesion, proliferation and differentiation into mature functional endothelium, and use these findings as design criteria to fabricate multi-functional biomaterials that will induce endothelium-mediated pancreatic islet normalization and/or survival of transplanted ß cells when targeted to diseased islets in the body. |
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Yinghua Guan, PhD
Training focus:Applied single molecular imaging techniques in vitro and in vivo
Training period:06/15/2009 – 06/14/2011Co-mentors:Jagesh Shah, PhD Sangeeta Bhatia, MD, PhD
It has been a significant challenge to quantitatively study the dynamic intracellular processes in live cells. These studies are essential for a thorough understanding of the underlying mechanisms regulating the signaling pathways and the transitions during cell proliferation and differentiation. As a SysCODE fellow I will apply my knowledge in single molecule detection instruments - confocal, wide-field and total internal reflection fluorescence microscopy - to study cell transformation, proliferation and differentiation during early odontogenesis by using single molecule and cell imaging technique in vitro and in vivo. The key element of this study will be to provide a comprehensive dynamic description of the live cell transformation under mechanical or chemical stress monitored with a number of known genetic markers. Specific aims: 1) Use quantitative models for cell behavior developed in Dr. Shah and Dr. Bhatia laboratories to measure degree of morphological changes in cell during early odontogenesis; 2) Study temporal kinetics for alleles known to be involved in odontogenesis (Pax9, Wnt, Msx, etc.) to validate and/or complement the construction of gene regulatory network (GRN) with live cell information; 3) Provide Proof of Principle results for reporter cell imaging protocol that can be adopted by other SysCODE teams. |
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Charlotte Hinault, PhD
Training focus:Analyses of the islet proteome
Training period:04/01/2008 – 10/23/2008Co-mentors:Rohit Kulkarni, MD, PhD Steven Gygi, PhD
The pancreatic islets of Langerhans, and especially the insulin-producing beta cells, play a central role in the maintenance of glucose homeostasis. Due to the importance of islets in the pathogenesis of both types of diabetes, a thorough understanding of islet biology is essential for the development of therapeutic strategies for the prevention, management and/or cure of the diseases. Our objective was to examine the islet proteome and compare the protein expression levels with gene expression patterns. A proteomic approach was undertaken to identify the proteins in adult islets isolated from male mice on a pure C57Bl/6 genetic background. Subsequent studies at distinct islets maturation stages as well as sorted beta cells from isolated adult mouse islets will complete this work in order to generate a complete database as a reference resource for the tissue engineering studies and for the diabetes research community. |
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Chong Wee Liew, PhD
Training focus:Analyses of the islet proteome
Training period:01/01/2009 – 12/31/2010Co-mentors:Rohit Kulkarni, MD, PhD Steven Gygi, PhD
The pancreatic islets of Langerhans, and especially the insulin-producing beta cells, play a central role in the maintenance of glucose homeostasis. The proposed experiments will allow the generation of a novel data base of proteins and gene expression in the endocrine pancreas (islets and beta cells) of a mammalian model (the mouse) -from adults and animal at different pancreatic islets maturation periods. These data will be useful for planning mammalian tissue engineering for pancreatic islets with specific reference to pancreatic beta cells. Specific Aims: a) A proteomic approach to identify the proteins in adult islets isolated from male mice on a pure C57Bl/6 genetic background. Due to the reason that islets constitute only ~2% of the pancreas we will use this initial set of experiments to generate data and in parallel standardize the methodology and fine-tune the technique to improve total protein yield. b) Subsequent studies will utilize islets pooled from appropriate numbers of male mice at distinct islets maturation stages as well as sorted beta cells from isolated adult islets. c) In subsequent periods of the Program we will focus on characterizing the proteome using islets from models that exhibit beta cell expansion. |
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David Nusinow, PhD
Training focus:Computational Methods for Proteomic Data Analysis
Training period:06/15/2009 – 06/14/2011Co-mentors:Shamil Sunyaev, PhD Richard Maas, MD, PhD
Proteomic methods present the opportunity to sharpen our global view of biological processes. However, developmental biologists have yet to widely embrace proteomics due to various difficulties with the methods. Perhaps the most notable difficulties include analyzing and interpreting the data from such experiments. One goal of the SysCODE project is to use proteomic data to understand organ composition, but to do so we must overcome these hurdles and find ways to integrate findings from proteomic experiments with that of whole-genome gene expression studies and classical genetic models. The goal of my project is to develop methods to do this, and apply them to the analysis of the mammalian organs that are the focus of the SysCODE effort. These analyses will be applied to further experimental design, and provide a cohesive framework to utilize proteomics in the study of organ development. |
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Alex Rolfe, PhD
Training focus:Computational Discovery of Regulatory Networks in Pancreatic Islets
Training period:06/01/2009 – 05/31/2011Co-mentors:David Gifford, PhD Doug Melton, PhD
Much of the work in regulatory network discovery has focused on integrating expression data, binding data, and motif presence to detect regulatory relationships, modules, and programs. Recent work in our lab and others has demonstrated the existence and importance of overlapping and interfering transcripts as regulatory mechanisms. I plan to use RNASeq experiments performed on pancreatic islets to identify examples of these mechanisms. By combining these newer mechanisms with our existing models, we should be able to more accurately explain the key features of gene regulation in the pancreas. The second focus of my work will be smaller networks that incorporate disparate data sources, for example metabolic pathway and protein interaction databases. Since these databases are often incomplete, we must adapt our computational methods to work around missing information and produce more detailed results for smaller sets of genes. |
