Environmental Pollutants and AHR pathway in Uterine Leiomyoma

Project: Research project

Project Details

Description

Our overall hypothesis is that increased Trp uptake and metabolism, Kyn production, and AHR pathway activation, as a result of mut-MED12 or high exposure to the environmental pollutant DEHP, promote cell survival and proliferation and lead to LM growth. Using a xenograft mouse model and genome-wide studies, we will test our hypothesis in the following Aims: (1) Define the functional role of the Trp-Kyn-AHR pathway in LM tumorigenesis. Hypothesis: elevated expression of the TDO2 enzyme in mut�MED12 LM causes Kyn overproduction that activates AHR and promotes proliferation and survival of smooth muscle cells and tumor growth. (2) Determine whether DEHP stimulates LM growth via activation of the Trp�Kyn-AHR pathway. Hypothesis: exposure to DEHP and its metabolite MEHHP upregulates the expression of Trp transporters to increase its uptake, resulting in increased Kyn production and AHR activation leading to LM cell survival and tumor growth. The study will link, for the first time, abnormal amino acid metabolism and LM growth, opening a new avenue for translational research and the development of novel therapeutics for LM.
StatusActive
Effective start/end date12/13/2210/31/27

Funding

  • National Institute of Environmental Health Sciences (5R01ES034753-02)

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