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Brian Lohse

Brian Lohse

Lektor

Primære forskningsområder

Research interests

- Epigenetics, with focus on disease, basic molecular mechanisms of action and pharmacology.

- Design and synthesis of mechanism based inhibitors for Histone modifyiers.

- Phage Display technology

Undervisnings- og vejledningsområder

I'm currently teaching all levels of University education: Ph.D.-Courses, Master courses and Bachelor courses.

Project supervision of Postdoc, Ph.d.-, Master and Bachelor students

Aktuel forskning

Chemical tools for Epigenetic Protein Families.

Epigenetic signaling controls gene regulation and repair, and is implemented in the cell via post-translational modifications such as phosphorylation, methylation and acetylation, of chromatin. The enzymes responsible for writing and erasing these chemical modifications that are located on the histone tails, may contribute to finding new therapeutic targets. New ligands can be used as chemical tools to gain insight into the impact of these modifications.

One enzyme family that is involved in these chemical modifications on the histone tails, are histone 3 lysine 9 (H3K9) demethylases. These demethylases have been shown to be involved in the development of a wide range of diseases, such as cancer, X-linked mental retardation and congenital heart disease, to mention a few. But H3K9 demethylases have also been linked to the regulation of self-renewal in embryonic stem cells, trough reversal of the H3K9 trimethylated marks at specific promoter regions, thereby preventing transcriptional repressors from binding.

Using phage display, enzyme kinetics and medicinal chemistry related strategies, we are studying the effect of various chemical tools synthesized in our group on the epigenetic protein families. Also we are investigating histone tail peptide modifications, such as phosphorylation, acetylation and methylation, through synthesizing mimics of the identified marks found in vivo. These in vitro experiments are used to asses the local effects of two marks on the same histone tail, also known as cross talk effects. This strategy is anticipated to contribute to our understanding of the dynamic processes underlying chromatin regulation and has the potential, through further development, to design specific inhibitors towards one member of the histone lysine demethylase family for epigenetic therapy.

Interesseområder

Research interests

- Synthesis of mechanism based inhibitors for Histone Demethylases, hereunder peptide chemistry.

- Assay development and drug delivery systems based on dendrimers.

- Transmembrane proteins, liposomes, enzymes, fluorescence techniques and photochemistry.

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