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Volatile metabolomics signatures of cancer and its olfactory detection
Our research is based on the assumption that the metabolic state of cancerous tissue alters the profile of volatile metabolites and that within mammalian olfactory genome there are functional olfactory receptors able to detect this unique metabolic signature. We have developed a novel approach to analyze various volatile and semi-volatile metabolites of cancer using gas chromatography and mass spectrometry and provided a “proof of principle” demonstration that a differential volatile profile of melanoma does indeed exist. Now, we are expanding these studies to other cancers and pathologies. Furthermore, in close collaboration with Professor Matsunami, we are pursuing studies related to in vivo activation and molecular profiling of mouse olfactory receptors using a phosphorylated S6 ribosomal protein as an indicator of activated olfactory sensory neurons.
The role of ectopic olfactory receptors
Our second line of our research is focused on “ectopic” olfactory receptors. These GPCRs are present both within the olfactory system and in various non-olfactory tissues. Thus, in addition to participating in odorant recognition, these “ectopic” ORs are active in sensing various metabolites. Several human “ectopic” ORs are overexpressed in different cancers, indicating that they may have an important, yet unknown role in human pathophysiology. What is the function of these ectopic receptors?
In order to answer this question, we are studying their endogenous ligands using both in silico and in vitro approaches, as we believe that by identifying their agonists and antagonists, we will be one step closer to unravel their function. Can metabolite-ligands signal via specific ORs to modulate cellular response such as proliferation, migration and invasion? These processes are essential for many physiological and patho-physiological conditions like embryonic development, growth, wound healing, immunologic responses, inflammation and cancer. We are analyzing the activation of these receptors and their consequent immediate, as well as chronic effects on cellular metabolism and phenotype.
Our research is based on the assumption that the metabolic state of cancerous tissue alters the profile of volatile metabolites and that within mammalian olfactory genome there are functional olfactory receptors able to detect this unique metabolic signature. We have developed a novel approach to analyze various volatile and semi-volatile metabolites of cancer using gas chromatography and mass spectrometry and provided a “proof of principle” demonstration that a differential volatile profile of melanoma does indeed exist. Now, we are expanding these studies to other cancers and pathologies. Furthermore, in close collaboration with Professor Matsunami, we are pursuing studies related to in vivo activation and molecular profiling of mouse olfactory receptors using a phosphorylated S6 ribosomal protein as an indicator of activated olfactory sensory neurons.
The role of ectopic olfactory receptors
Our second line of our research is focused on “ectopic” olfactory receptors. These GPCRs are present both within the olfactory system and in various non-olfactory tissues. Thus, in addition to participating in odorant recognition, these “ectopic” ORs are active in sensing various metabolites. Several human “ectopic” ORs are overexpressed in different cancers, indicating that they may have an important, yet unknown role in human pathophysiology. What is the function of these ectopic receptors?
In order to answer this question, we are studying their endogenous ligands using both in silico and in vitro approaches, as we believe that by identifying their agonists and antagonists, we will be one step closer to unravel their function. Can metabolite-ligands signal via specific ORs to modulate cellular response such as proliferation, migration and invasion? These processes are essential for many physiological and patho-physiological conditions like embryonic development, growth, wound healing, immunologic responses, inflammation and cancer. We are analyzing the activation of these receptors and their consequent immediate, as well as chronic effects on cellular metabolism and phenotype.
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Molecular pharmacologyno. 1 (2024): 21-32
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