Internal Contamination (USUHS)
Abstract
Internal Contamination (USUHS): Radioactive material can enter the body by a variety of pathways including ingestion, inhalation, and wound contamination. While some internalized isotopes will be naturally eliminated from the body, many others are not. They remain immobile or are transported and deposited to other organs where they continually irradiate the surrounding tissue. This chronic internal radiation exposure can cause unrepairable cellular damage eventually leading to death. This Program uses innovative organic chemical synthesis (Molecularly Imprinted Polymer (MIPs), the novel development of gastrointestinal organ-on-chip technology and studies on the gut microbiome approaches to address this pressing health concern. First, MIPs have been shown to be highly-efficient and specific metal chelators. In order to expand the applicability of this approach, we synthesize chelation moieties onto dendritic polymer (dendrimers). Dendrimers are non-toxic, highly branched three-dimensional structures whose synthesis can be tightly controlled to yield a product of precise shape and size, thus, becoming highly-specific metal binders and can be tested as therapeutic agents for internalized radionuclides. Second, the development of organ-on-chip technology will lead to minimized use of animal models in the study of internal radiation effects. The model utilizes intestinal cell types and three dimensional architecture to mimic intestinal physiology and pathology. This novel 3D culture system will mimic the in vivo animal model and provide new stratagem to investigate the radiation induced gastrointestinal syndrome. This program also explores the internal radiation effects on the gut microbiome, understanding that alterations in the microbiome will share similar pathologic characteristics such as reduced bacterial diversity and the emergence of opportunistic pathogens that provide diagnostics and therapeutic targets. Determining the effect of ionizing radiation on altering the gut microbiome will reveal the effect on physiology, cell survival, inflammation, cytokine expression and metabolism.
Document Details
- Document Type
- Accomplishment
- Publication Date
- Oct 01, 2024
- Source ID
- 6a67dad4db26378204bbeb64c8c92ca2