Research Projects

The aryl hydrocarbon receptor (AHR) modulates both tumor’s intrinsic malignancy and anti-tumor immunity, thereby acting as a master regulator of tumor progression. However, in a very cell type-, ligand- and context specific manner, AHR can exert both tumor-promoting and tumor-suppressive effects. These opposing effects of AHR are likely derived from the complexity of AHR activation mechanisms and biological functionality. Even though the role of AHR in tumor maintenance and aggression has been widely been reported, in contrast the mechanism of AHR crosstalk with other signaling pathways and AHR agonist-induced carcinogenesis has largely escaped scientific scrutiny. Therefore, to utilize the AHR as a viable target entity for cancer therapy, an exhaustive understanding of AHR biology, its crosstalk and its mechanistic roles in not just tumor progression and maintenance but also in tumorigenesis is of utmost importance. However, until very recently the context specificity of AHR biological functions prevented comprehensive investigation of AHR across all human cancers. Combining the power of natural language processing (NLP) and gene expression analysis, we have previously developed and patented a pan-tissue AHR signature, which in combination with the proposed laboratory experimentations using gene expression analysis, metabolic as well as protein analysis, places us in a unique position to investigate and delineate the AHR activation mediated carcinogenesis. This proposed study to identify (a) AHR cross talk with other signaling pathways, (b) the molecular mechanisms underlying the AHR activation mediated carcinogenesis and (c) theranostic potential of AHR activation, will facilitate (i) a clear understanding of AHR crosstalk mediated tumor maintenance and progression; thus aiding the development of tailored clinical interventions for targeting AHR dependent cancers for precision therapies; (ii) the stratification of cancer patients, thus enabling identification of patients in which AHR activation contributes to tumorigenesis and to subsequent clinical outcomes.