Selection of publications and patents of my research work.
Zertifikate und Zertifizierungen
Metabolomics in Personalized Medicine
Metabolomics is the newest member of the "omics" family. Metabolomics is the totality of all metabolites such as amino acids, fatty acids, carbohydrates or other intermediates of an individual at a given time. So, while the genome is the blueprint for an individual, the metabolome describes the current state of an individual. Accordingly, "show me your metabolome and I'll tell you how you're doing," metabolomics is playing an increasing role in diagnostics and personalized medicine. The German company Numares is the first company that has developed and commercialized a metabolomics-based in vitro diagnostic test system.
Kaletta T. und Proll C.: „Der Stoffwechsel in der Diagnostik …: Neue Möglichkeiten der personalisierten Medizin mit Metabolomics“. Going Public - Life Sciences (2016), 22-23
Nicotinic Receptor Modulators for Treatment of Alzheimer's
Alzheimer's disease is the most common dementia. Around 1.6 million people are affected in Germany alone (Deutsche Alzheimer Gesellschaft, 2018). Unfortunately, despite intensive research, there are no new effective treatment options. The German company Galantos Pharma has developed an allosteric modulator of the alpha7 nicotinic acetylcholine receptor to improve the cognitive performance of Alzheimer's patients. The advantage of this modulator is its dual mechanism of action with fewer side effects. The compound, alpha-1062, is currently under clinical development (Phase II / III) by Alpha Cognition.
Ludwig J., Rabe H., Höffle-Maas A., Samochocki M., Maelicke A., Kaletta T.: Directed mutagenesis of nicotinic receptors to investigate receptor function. InTech (2012), in: David Figurski, ed.: Directed Mutagenesis.
New Small Molecules for Treatment of Atrial Fibrillation
Atrial fibrillation is a heart rhythm disorder that affects about 2% of the German population. Patients experience palpitations, for example. Even though atrial fibrillation is usually not acutely life-threatening, there is a risk of complications such as stroke or heart failure. About 20% of strokes are due to atrial fibrillation (German Stroke Society, 2013). The Belgian company Devgen has developed modulators for potassium channels up to the preclinical stage with the aim of suppressing atrial fibrillation episodes. For this purpose, in addition to classical electrophysiology, the model organism C. elegans was used in high-throughput screening campaigns.
Patent: WO2007138110A2: Compounds that interact with ion channels from the KV family; Erfinder: P. Blom, O. Defert, T. Kaletta, D. Leysen
The Role of Model Organisms in Drug Discovery
Model organisms such as the nematode C. elegans are ideal for screening new drug targets in a physiological context. This means testing the effect of 1000ths of chemical substances on a protein that is important for the therapy of a disease. It plays a major role that such a test systems recapitulates critical disease mechanisms as good as possible. At the beginning of this century, this was impossible with 2D cell cultures. Can a human drug have any specific effect at all in C. elegans? Yes, the compounds described above were discovered in a high-throughput screen with C. elegans and further validated in mammalian models.
Kaletta T. and Hengartner M. O.: Finding function in novel targets: C. elegans as a model organism. Nature Reviews Drug Discovery (2006) 5, 387-398.
Polycystic Kidney Disease - Mastering Target Validation
With the sequencing of the human genome, the pharmaceutical industry was suddenly flooded with an incredible number of new genes that could potentially help in the development of new drugs. But how useful is such a new gene - a drug target - if you do not understand its function? Take the polycystins as an example, which are defective in the most common genetic disease, polycystic kidney disease (ADPKD). Devgen has used C. elegans to elucidate the function of the polycystins. The polycystins are pressure- and mechanosensors required for the development of the tubular system of the kidney as was years later confirmed in mice.
Kaletta T., Van der Craen M., Van Geel A., Dewulf N., Bogaert T., Branden M., King K. V., Buechner M., Barstaed R., Hyink D., Li H. P., Geng L., Burrow C., Wilson P.: Towards understanding the polycystins. Nephron (2003) 93, E9-E17.
Discovery of a New Paradigm in Embryogenesis
Everyone knows the "chicken-egg problem". But how does a simple egg actually develop into a chicken? This is the subject of developmental biology. One established model is the nematode C. elegans. One of its advantages is its transparency, which allows to observe embryonic development in real time under a microscope. Thus, one can precisely follow when and how the intestine or the nervous system develops. But how does a cell actually know that it is supposed to develop into an intestinal or a nerve cell? My thesis provided the answer: In C. elegans, each cell has a binary code that determines whether it will become an intestinal, nervous or any other cell.
Kaletta T., Schnabel H., Schnabel R.: Binary specification of the embryonic lineage in Caenorhabditis elegans. Nature (1997) 390, 294-8.
(The principle of binary specification of blastomers, embryonic precursor cells, is one of the five accepted paradigms of the embryogenesis of C. elegans )
Saenez-Narciso et.al.: The embryonic cell lineage of C. elegans. Wiley Bioassays (2014) 36, 1-3.)