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BACKGROUND & AIMS Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that they are highly radiosensitive. Cycling crypt base columnar(More)
Radiation gastrointestinal (GI) syndrome is a major lethal toxicity that may occur after a radiation/nuclear incident. Currently, there are no prophylactic countermeasures against radiation GI syndrome lethality for first responders, military personnel, or remediation workers entering a contaminated area. The pathophysiology of this syndrome requires(More)
Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5(+) crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regulation of the ISC compartment after(More)
Acid sphingomyelinase (ASMase) is a key initiator of sphingomyelin/ceramide signal transduction activated by many stress stimuli. Over the past two decades, much progress has been made in defining the clinical relevance of sphingomyelin/ceramide signaling in numerous diseases using ASMase knockout mice. Organs that operate this pathway are numerous and the(More)
BACKGROUND Bone-related complications are commonly reported in cancer patients receiving radiotherapy and are collectively referred to as the abscopal effect of irradiation, the mechanism of which remains poorly understood. When patients receive targeted radiotherapy to a tumor, the local skeleton is exposed to radiation, particularly within the bone(More)
While it is known that irradiation can induce local and systemic bone loss over time, how focal irradiation induces systemic bone complications remains unclear. Immune cells are thought to be crucial to bone homeostasis, and abnormal immune cells lead to serious disruption of bone homeostasis, such as in acute lymphoblastic leukaemia. This disruption(More)
Although small and large intestines possess seemingly similar Wnt-driven leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)+ adult epithelial stem cells, we report here that the two organs exhibit distinct mechanisms of tissue response to ionizing radiation. Employing Lgr5-lacZ transgenic mice and Lgr5 in situ hybridization, we found colonic(More)
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