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Hematopoietic stem cells can be injured. The Borghesi lab studies the pathways that maintain stem cell quality. Multipotent stem cells are the source of all white blood cells of the immune system. Infection, radiation exposure, chronic autoimmunity and even chronologic aging can diminish stem cell function. Indeed, the elderly amongst us are one of the hardest groups to vaccinate effectively due, in part, to diminished lymphocyte production. We are working to determine if stem cell injury can be reversed. |
Our work over the last decade defines a major role for the E47 transcription factor in regulating hematopoietic stem cell function as well as downstream B lymphocyte production and antibody formation. In the absence of E47, stem cells proliferate to exhaustion and fail to produce antibody-secreting B lymphocytes. Moreover, we have linked E47 overexpression to the B cell cancer CLL. Our findings provide a molecular mechanism for the stem cell exhaustion that frequently accompanies diseases of chronic inflammation, and suggests new opportunities for therapy. |
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