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RESEARCH PROJECTS

Historically, the main interest of the lab was calcium signaling. Although this interest has not been abandoned, a number of other lines of research have been added. The lab now covers a number of fields of pharmacology, ranging from basic signal transduction mechanisms to pharmacogenetics and drug use.

Pyridine nucleotide second messengers

There is now ample evidence that, alongside IP3, the pyridine nucleotide derivatives cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) can act as second messengers, releasing calcium from intracellular stores. In particular, the lab focuses on the biochemical and pharmacological characterisation of the pathways involved in NAADP-induced Ca2+-release.

Deregulation of calcium signaling in neurodegenerative diseases

It is well established that changes in cytosolic or nuclear calcium levels can, directly or indirectly, either activate or inactivate transcription factors. The lab is interested in understanding the role of the calcium/calmodulin dependent phosphatase calcineurin in mediating calcium-dependent gene expression in neurons. In particular, the main focus of the lab at present is to understand whether the Abeta peptide, thought to mediate the development of Alzheimer’s disease, can induce Ca2+-dependent transcriptional changes in glial cells.

Nicotinamide phosphoribosyl transferase inhibitors in cancer therapy

Nicotinamide phosphoribosyl transferase (NAMPT) is an enzyme involved in the synthesis of NAD, and in particular it is involved in the recycling pathway. This enzyme has been shown to be up-regulated in a number of tumors and in inflammatory states. Furthermore, a soluble, extra-cellular form of this protein has been described (often under the name visfatin or PBEF), which is also increased in cancer patients and in inflammatory states. The lab, via the use of cell biology, molecular biology and pharmacological tools, is interested in unraveling the role of this enzyme in cancer and inflammation and to explore the therapeutic potential of NAMPT inhibitors.

Table1: NAMPT and cancer

Rapid synthetic methods for the generation of pharmacologically active drugs

In collaboration with the Synthetic Medicinal Chemistry group of the Department, the lab seeks to find novel chemical entities as anticancer agents. Most efforts are concentrated around tubulin and nicotinamide phosphoribosyl transferase inhibitors. While rapid synthetic methods (such as click chemistry) characterize most projects, other synthetic approaches are also considered.

Pharmacogenetics and pharmacogenomics

One of the interests of the lab is the understanding of how single nucleotide polymorphisms can affect drug action. Projects are undergoing in the field of nephrology, radiotherapy, neurology, pain, and oncology. The lab is also a founding member of the University Center CRIFF.

Meta-analyses of pharmacogenetic studies

Meta-analyses is an invaluable tool to provide conclusive data on the true impact of a particular medical intervention. While in the pharmacological field this approach is well established, pharmacogenetics appears to have been left behind. Contrasting reports on the role of particular SNPs appear in the literature, but few groups are interested in attempting to use such data for meta-analyses. We have now started to use such approach in the filed of oncology and nephrology.

Correct use of pharmaceutical resources

The lab is also interested in appropriateness of pharmaceutical resources, with particular emphasis on the correct use of generic and biosimilar drugs as well as a correct assessment of innovation and rapid access of new drugs to patients.


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