Browsing by Author "Ma, Roger"

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    Characterizing the pro-inflammatory cytokine response by dendritic cells upon exposure to PrP proteins
    (2013-09-24) Ma, Roger; Czub, Markus
    Dendritic cell (DC) interaction with infectious prions (PrPSc) represents an important part of prion pathogenesis. Previous studies have shown that DCs are likely among the first immune cells to interact with PrPSc after oral exposure. This study looks at the initial exposure of PrPSc on DC activation by measuring TNFα and IL-12 production. There was no significant production of TNFα or IL-12 by bone marrow derived DCs (BMDC) after exposure to PrPSc infected brain homogenate, however, BMDCs had lower capacity to produce IL-12 after secondary stimulation with LPS. Semi-purified PrPSc also did not activate BMDCs, however, the recombinant MoPrP 23-231 and MoPrP 90-231 elicited TNFα and IL-12 production. These results may not be surprising since PrPSc closely resembles cellular PrPC and therefore, DCs recognized PrP in brain homogenates as self-antigens. However, MoPrP 23-231 and MoPrP 90-231 were recognized as foreign antigens since the proteins were produced in bacteria.
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    Origin and diversification of tissue-resident fibroblasts
    (2021-03-12) Ma, Roger; Huang, Peng; Grewal, Savraj; Mains, Paul
    Every cell within a multicellular organism contains the same genome and ultimately originates from a single cell. Despite this, a vast array of cell types is created during development. Understanding how a single progenitor can differentiate into distinct cell types is one of the fundamental questions in developmental biology. For example, while it is known that the somites generate much of the axial body, the specific mechanisms of how this occurs remains poorly understood. In this thesis, I use the zebrafish sclerotome as a model to study how different cell types can be generated from a common pool of progenitor cells. During development, the sclerotome is subdivided from the somite and gives rise to the axial skeleton, cartilage and tendons. In Chapter 2, I characterize sclerotome development in zebrafish and identify a novel dorsal sclerotome domain unique in zebrafish. Active hedgehog signaling is required for the migration of and maintenance of sclerotome-derived cells. Lineage analysis reveals that the sclerotome progenitors give rise to tenocytes (tendon fibroblasts) in a stereotypical manner. In Chapter 3, I ask how sclerotome progenitors diversify into multiple fibroblast subtypes. Using single cell lineage analysis, reveals that the sclerotome is multipotent and generates a variety of fibroblasts in the zebrafish trunk. BMP signaling is required for the generation and maintenance of a subset of sclerotome-derived fibroblasts, the fin mesenchymal cells. Together, my work shows that the zebrafish sclerotome is the embryonic origin of a diverse population of tissue-resident fibroblasts and can be a good model to study cell type diversification.