Browsing by Author "Jhamb, Deepali"

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    The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities
    (Public Library of Science, 2015) Chen, Xiaoping; Song, Fengyu; Jhamb, Deepali; Li, Jiliang; Bottino, Marco C.; Palakal, Mathew J.; Stocum, David L.; Department of Biology, School of Science
    We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.
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    Condition-specific differential subnetwork analysis for biological systems
    (2015-04) Jhamb, Deepali; Liu, Xiaowen; Li, Lang; Liu, Yunlong; Palakal, Mathew J.; Stocum, David L.
    Biological systems behave differently under different conditions. Advances in sequencing technology over the last decade have led to the generation of enormous amounts of condition-specific data. However, these measurements often fail to identify low abundance genes/proteins that can be biologically crucial. In this work, a novel text-mining system was first developed to extract condition-specific proteins from the biomedical literature. The literature-derived data was then combined with proteomics data to construct condition-specific protein interaction networks. Further, an innovative condition-specific differential analysis approach was designed to identify key differences, in the form of subnetworks, between any two given biological systems. The framework developed here was implemented to understand the differences between limb regeneration-competent Ambystoma mexicanum and –deficient Xenopus laevis. This study provides an exhaustive systems level analysis to compare regeneration competent and deficient subnetworks to show how different molecular entities inter-connect with each other and are rewired during the formation of an accumulation blastema in regenerating axolotl limbs. This study also demonstrates the importance of literature-derived knowledge, specific to limb regeneration, to augment the systems biology analysis. Our findings show that although the proteins might be common between the two given biological conditions, they can have a high dissimilarity based on their biological and topological properties in the subnetwork. The knowledge gained from the distinguishing features of limb regeneration in amphibians can be used in future to chemically induce regeneration in mammalian systems. The approach developed in this dissertation is scalable and adaptable to understand differential subnetworks between any two biological systems. This methodology will not only facilitate the understanding of biological processes and molecular functions which govern a given system but also provide novel intuitions about the pathophysiology of diseases/conditions.
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    The Connection Between Regenerative Features of Salamander Limbs and Mammalian Somatic Cells
    (Office of the Vice Chancellor for Research, 2010-04-09) Rao, Nandini; Jhamb, Deepali
    The unique regenerative feature of urodele salamander limbs is their natural ability to dissolve tissue organization and re-program somatic cells to adult stem-like cells at the site of an amputation to create a blastema that self-organizes the missing limb parts. To understand this information, we used quantitative LC/MS/MS peptide separation to analyze temporal changes in proteins after amputation of axolotl hind limbs. The information from this study will be useful in devising chemical induction strategies to reprogram mammalian somatic cells or activate resident stem cells directly at the site of injury to regenerate damaged tissues and appendages.
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    Proteomic analysis of fibroblastema formation in regenerating hind limbs of Xenopus laevis froglets and comparison to axolotl
    (Springer Nature, 2014-07-25) Rao, Nandini; Song, Fengyu; Jhamb, Deepali; Wang, Mu; Milner, Derek J.; Price, Nathaniel M.; Belecky-Adams, Teri L.; Palakal, Mathew J.; Cameron, Jo Ann; Li, Bingbing; Chen, Xiaoping; Stocum, David L.; Oral Pathology, Medicine and Radiology, School of Dentistry
    Background: To gain insight into what differences might restrict the capacity for limb regeneration in Xenopus froglets, we used High Performance Liquid Chromatography (HPLC)/double mass spectrometry to characterize protein expression during fibroblastema formation in the amputated froglet hindlimb, and compared the results to those obtained previously for blastema formation in the axolotl limb. Results: Comparison of the Xenopus fibroblastema and axolotl blastema revealed several similarities and significant differences in proteomic profiles. The most significant similarity was the strong parallel down regulation of muscle proteins and enzymes involved in carbohydrate metabolism. Regenerating Xenopus limbs differed significantly from axolotl regenerating limbs in several ways: deficiency in the inositol phosphate/diacylglycerol signaling pathway, down regulation of Wnt signaling, up regulation of extracellular matrix (ECM) proteins and proteins involved in chondrocyte differentiation, lack of expression of a key cell cycle protein, ecotropic viral integration site 5 (EVI5), that blocks mitosis in the axolotl, and the expression of several patterning proteins not seen in the axolotl that may dorsalize the fibroblastema. Conclusions: We have characterized global protein expression during fibroblastema formation after amputation of the Xenopus froglet hindlimb and identified several differences that lead to signaling deficiency, failure to retard mitosis, premature chondrocyte differentiation, and failure of dorsoventral axial asymmetry. These differences point to possible interventions to improve blastema formation and pattern formation in the froglet limb.