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In modern society, the average human being is exposed to thousands of chemicals every day. Many of these chemicals are capable of interfering with cellular signaling pathways which are regulated by intracellular receptors that belong to the Nuclear Receptor superfamily. These chemicals are known as EDCs or Endocrine Disruptive Chemicals. Much of Ingemar Pongratz’s research has focused on the effects of EDCs.
Ingemar Pongratz work was focused on how certain chlorinated compounds affect human health. Ingemar Pongratz work on dioxins and how dioxins bind a an intracellular receptor called AhR (Aryl Hydrocarbon Receptor).
The work of Ingemar Pongratz has been of basic science character. During the course of the investigation, Ingemar and his coworker made several key finding such as identifying one AhR associated protein as a key regulator of the estrogen receptor and thus for the first time provided evidence why the AhR has the ability to interfere with hormone receptor signaling. In addition, Ingemar and co-workers identified for the first time the enzymatic pathway that generated the endogenous ligand for the AhR demonstrating that this receptor is a potential pharmaceutical target. Ingemar Pongratz is currently in the process on following up these observations on a commercial basis.
Personal Work
The AhR bind to pollutants such as dioxin and to certain nutrients such as carbazoles and indoles and regulate the cellular response triggered by this compounds. Once dioxin binds to the AhR the cells responds with an increase in gene expression.
At the same time, dioxins, through the AhR, interfere with sex hormone signaling, most notably female hormones. Ingemar Pongratz and his group demonstrated that there is extensive crosstalk between the AhR and sex hormone signaling and that certain auxiliary factors are shared between these cellular pathways.
When one system is activated it competes with the other; an effect that ultimately can lead to disease. This observation, however, also has pharmaceutical potential.
There are certain conditions where overactive sex hormone receptor activity is linked to disease, such as breast cancer. Lowering their activity by activating the AhR is therefore, at least in theory an interesting source of new pharma compounds.
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The work of Ingemar Pongratz has been of basic science character. During the course of the investigation, Ingemar and his coworker made several key finding such as identifying one AhR associated protein as a key regulator of the estrogen receptor and thus for the first time provided evidence why the AhR has the ability to interfere with hormone receptor signaling.
In addition, Ingemar and co-workers identified for the first time the enzymatic pathway that generated the endogenous ligand for the AhR demonstrating that this receptor is a potential pharmaceutical target. Ingemar Pongratz is currently in the process on following up these observations on a commercial basis.