项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

FRIEDEN, LESLIE A

项目受资助机构

STATE UNIVERSITY OF NEW YORK AT BUFFALO

项目编号

1K18DE029526-01

立项年度

2020

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

94393.00美元

学科

Aging; Dental/Oral and Craniofacial Disease; Genetics; Human Genome; Infectious Diseases; Microbiome;

学科代码

未公开

基金类别

Other Research Related

关键词

未公开

参与者

KIRKWOOD, KEITH L

参与机构

NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH

项目标书摘要：PROJECT SUMMARY Research: With advancing age, the immune system undergoes dynamic changes characterized by both impairment of adaptive immunity and activation of low-grade chronic inflammation. This chronic activation of inflammation associated with aging or `inflammaging'. Tristetraprolin (TTP) is an RNA binding protein that post- translationally binds to adenylate-uridylate?rich elements in the 3?-UTR of target mRNAs (including key pro- inflammatory mRNAs e.g. TNF?, COX-2 and IL-6) to promote their rapid turnover. Importantly, the project laboratory has demonstrated that failure to regulate expression of cytokines at the posttranscriptional level contributes to chronic inflammation and spontaneous alveolar bone loss with age in TTP-/- mice compared to age/sex match controls. Thus, TTP expression appears to be essential for alveolar bone homeostasis in an age- dependent manner. Data in this application and recently published data strongly support the concept that macrophages and myeloid-derived suppressor cell (MDSC) populations are expanded with age in TTP-/- mice, with concomitant reduction in lymphocyte populations. Taken together, these results support the notion that TTP may be a critical intrinsic factor of inflammaging and myeloid lineage expansion/differentiation that contributes towards skeletal homeostasis. For this K18 application, it is proposed to use data sets generated already under 5R01DE028258, to examine the role of the microbiome in contributing towards the TTP null hyperinflammatory phenotype and understand if MDSC populations from oral and non-oral sources have different expression profiles by single cell RNA sequencing. Fellowship training plan/environment: The applicant has assembled a strong mentoring team who have a long history of working together and training scientists to become successful independent investigators. The proposed project will allow the applicant to integrate his translation research portfolio with bioinformatics, which will foster the perspectives and skills necessary to continue to be a successful oral biologist.