Molecular basis for dietary chemoprevention

饮食化学预防的分子基础

• 批准号: 10348744
• 负责人: Robert Stephen Chapkin
• 金额: $ 80.62万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10348744
• 关键词: Agonist; Biomedical Research; Botanicals; Cancer Patient; Cell membrane; Chronic Disease; Colon; Data; Diet; Early Diagnosis; Epithelial Cells; Funding; Goals; Head; Human; KRAS2 gene; Ligands; Link; Liquid substance; Malignant - descriptor; Malignant Neoplasms; Molecular; Nuclear Envelope; Obesity; Oncogenic; Pharmaceutical Preparations; Prevention; Proteins; Reducing Agents; Reporting; Research; Role; Safety; Signal Transduction; Time; amphiphilicity; anticancer research; biophysical properties; cancer prevention; cancer risk; colon cancer risk; design; dietary; dietary chemoprevention; experience; healthcare community; intestinal epithelium; microbial; nanoscale; novel; public health relevance; receptor; response; stem cell homeostasis; stemness; survivorship; translational impact; tumorigenesis

 DESCRIPTION (provided by applicant): If the healthcare community hopes to head off the impending cancer storm, we need to get more serious about cancer prevention soon. Unfortunately, less than 1.5% of total biomedical research funding is targeted to early detection and prevention of chronic disease. With respect to all human malignancies, 35% are linked directly to diet and an additional 14-20% to obesity. Consistent with these data, cancer risk can be lowered by 36% when humans adhere to healthy dietary principles. Establishing a causal role for cancer dietary chemoprevention approaches that are free of safety problems intrinsic to drugs administered over long periods of time would have a major translational impact in cancer prevention and patient survivorship. Therefore, our overall goal is to better understand the molecular (nuclear and plasma membrane targeted) mechanisms linking intestinal epithelial cell responses to diet-derived natural botanical products, and endogenous (gut microbial) modifiers of colon cancer risk. Our extensive experience in the dietary chemoprevention field has afforded us with a unique mechanistic perspective in this regard. We propose to pursue two novel research themes. Project 1 will assess the combined agonist and antagonistic role of Arylhydrocarbon Receptor (AhR) ligands as determinants in colon stem cell homeostasis and malignant transformation. Our studies to date indicate that AhR ligands have profound short-term effects on stemness, and may be beneficial in terms of malignant transformation. Project 2 is designed to determine whether by altering cell membrane liquid ordered nanoscale assemblies, and therefore protein spatial localization and signaling, that select amphiphilic dietary agents will reduce oncogenic K-Ras signaling leading to reduced tumorigenesis. This strategy is consistent with recent reports from our lab and others that select amphiphilic agents, through direct modulation of the biophysical properties of the plasma membrane, alter oncogenic K- Ras nanoclustering and suppress signal transduction.



项目成果

Health Benefits of Coffee Consumption for Cancer and Other Diseases and Mechanisms of Action.

• DOI: 10.3390/ijms24032706
• 发表时间: 2023-01-31
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 影响因子: 5.6
• 作者: Safe, Stephen;Kothari, Jainish;Hailemariam, Amanuel;Upadhyay, Srijana;Davidson, Laurie A.;Chapkin, Robert S.
• 通讯作者: Chapkin, Robert S.

Diet and Gut Microbes Act Coordinately to Enhance Programmed Cell Death and Reduce Colorectal Cancer Risk.

• DOI: 10.1007/s10620-020-06106-8
• 发表时间: 2020-03
• 期刊: Digestive diseases and sciences
• 影响因子: 3.1
• 作者: Chapkin RS;Navarro SL;Hullar MAJ;Lampe JW
• 通讯作者: Lampe JW

Sex-dependent differences in the stress mitigating and antidepressant effects of selective aryl hydrocarbon receptor modulators.

选择性芳烃受体调节剂的缓解压力和抗抑郁作用存在性别依赖性差异。

• DOI: 10.1016/j.jad.2022.09.155
• 发表时间: 2022
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Madison,CaitlinA;Debler,RoannaA;Vardeleon,NathanI;Hillbrick,Lauren;Jayaraman,Arul;Safe,Stephen;Chapkin,RobertS;Eitan,Shoshana
• 通讯作者: Eitan,Shoshana

AdipoRon Attenuates Wnt Signaling by Reducing Cholesterol-Dependent Plasma Membrane Rigidity

• DOI: 10.1016/j.bpj.2019.09.009
• 发表时间: 2020-02-25
• 期刊: BIOPHYSICAL JOURNAL
• 影响因子: 3.4
• 作者: Salinas, Michael L.;Fuentes, Natividad R.;Chapkin, Robert S.
• 通讯作者: Chapkin, Robert S.

From crypts to enteroids: establishment and characterization of avian intestinal organoids.

• DOI: 10.1016/j.psj.2021.101642
• 发表时间: 2022-03
• 期刊: Poultry science
• 影响因子: 4.4
• 作者: Zhao D;Farnell MB;Kogut MH;Genovese KJ;Chapkin RS;Davidson LA;Berghman LR;Farnell YZ
• 通讯作者: Farnell YZ