Project Details
Description
PROJECT SUMMARY
Mammary gland development requires complex interactions between mammary epithelial cells and
their surrounding environment. Tissue resident macrophages are present in the mammary gland in close
association with developing epithelial structures and within the adipose stroma, and are known to be important
for contributing to mammary gland development and maintaining tissue homeostasis. Understanding these
mechanisms is critical for determining the consequences of altered macrophage function on loss of
homeostasis and promotion of tissue specific disease, such as tumorigenesis. The goal of this project is to
delineate the mechanisms that maintain tissue resident macrophages in the mammary gland in a homeostatic
state and to determine whether the altering these mechanisms impacts mammary gland development. In
preliminary studies, we have developed a novel method for identifying and isolating distinct populations of
resident macrophages from the mammary gland, including macrophages associated with epithelial structures
and those associated with stromal regions. Based on preliminary studies, we propose that signal transducer
and activator of transcription (STAT) pathways are key regulators of resident macrophages in the mammary
gland and that deregulation of these pathways results in the formation of macrophages that create a
permissive environment for tumorigenesis. Proposed studies will 1) determine the source and localization of
tissue resident macrophage populations during mammary gland development, 2) demonstrate the importance
of STATs as key transcriptional regulators of tissue resident macrophages in the mammary gland and 3)
determine the effects of inflammatory factors on resident macrophage function in the mammary gland. Recent
studies have focused on understanding the mechanisms driving tissue resident macrophage function and their
contributions to tissue development and homeostasis. However, relatively little is known regarding the
mechanisms driving resident macrophage function in the mammary gland. Understanding these mechanisms
will provide insights into how alterations in resident macrophage function, such as by local or systemic
inflammatory signals, impact epithelial morphogenesis and contribute to cancer risk.
Status | Finished |
---|---|
Effective start/end date | 8/15/18 → 5/31/23 |
Funding
- National Institute of Child Health and Human Development: $377,300.00
- National Institute of Child Health and Human Development: $385,000.00
- National Institute of Child Health and Human Development: $377,300.00
- National Institute of Child Health and Human Development: $385,000.00
- National Institute of Child Health and Human Development: $385,000.00
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