Born and raised in Dordrecht, the Netherlands, Dr. Jerome Korzelius studied Biology at Utrecht University, where he graduated in 2003. After a brief period working as a research technician in his lab at Harvard Medical School, he followed his supervisor Sander van den Heuvel back to Utrecht University to pursue his PhD on cell cycle regulation in C. elegans. After graduating in 2010, he joined the lab of Bruce Edgar at the University of Heidelberg as an EMBO Long-Term Fellow to work on stem cell regulation using the intestine of the fruit fly (Drosophila melanogaster). After a brief post-doc studying the genetics of complex chromosomal disorders in patients at the Hubrecht Institute/UMCU Medical Center in Utrecht, he returned to working with Drosophila and joined up with Heinrich Jasper to set up a Collaboration Group between the Buck Institute on Aging and the FLI-Leibniz Institute on Aging in Jena, Germany. He was awarded a DFG-German Research Council grant to study entero-endocrine cell differentiation in the intestine. In late 2018, he continued this work at the Max Planck Institute for Biology of Aging in Cologne, Germany in the Department of Prof. Dame Linda Partridge. Dr. Korzelius joined the School of Biosciences at the University of Kent in 2020.
Ageing is accompanied by the gradual deterioration of many tissues in the body. Many organisms have tissue-resident adult stem cells to be able to replace dead and dying cells in tissues with high turnover, such as the skin, blood and the intestine. Hence, preserving the regenerative potential of these adult stem cells is a promising avenue in preventing age-related tissue decline. The Korzelius lab is interested in how adult stem cell differentiation is regulated in the intestine and how these regulatory mechanisms are affected by ageing. For this, we use the fruit fly Drosophila melanogaster as a model system due to its short lifespan, powerful genetics and conserved mechanisms of ageing.
Our previous work focused on the transcriptional control of stem cell maintenance and differentiation in the fly intestine and identified the Snail-type transcription factor Escargot as a critical factor for intestinal stem cell (ISC) maintenance (Korzelius et al., EMBO Journal 2014). Snail-type transcription factors have established roles as markers as well as drivers for cancer metastasis. This work connected well with work in mammals highlighting a role for Snail-type factors in adult stem cell maintenance in the intestine (Horvay et al., EMBO Journal 2015) and mammary gland (Guo et al., Cell 2012).
More recently, our work has focused on the differentiation of entero-endocrine (EE) cells of the Drosophila intestine. EE cells play a crucial role in the intestine of animals to relay signals about food, energy and pathogens both locally as well as systemically to distant tissues such as the brain, liver and fat tissue. We identified a pivotal role for the transcription factor Klumpfuss (Klu) in the determination of EE cell fate (Korzelius et al., Nature Communications 2019). Loss of Klu leads to an increase in EE cell differentiation. We are currently investigating the functional consequences of the loss of Klu for the intestine, as well as further looking into the role of several Klu target genes in EE cell differentiation.
Age affects all tissues of the body, but age-related changes in adult stem cells can be particularly harmful. Not only does age-related damage impair their potential to self-renew, mutations in ASCs can promote uncontrolled division and expansion of these cells, leading to the development of cancer. In Drosophila, both the proliferation and differentiation of intestinal stem cells is severely impaired with advanced age, eventually leading to death of the animal. Interventions in age-related pathways in ISCs can improve both gut health and lifespan (Biteau et al., PLoS Genetics 2010). In collaboration with Alessandro Ori (FLI-Leibniz Institute on Ageing), we have explored the mRNA and protein level changes in the intestine of Drosophila. From this, we have generated a set of high-confidence targets that change their expression at both protein and mRNA levels during ageing. We are currently addressing the role of several of these targets in preserving gut health and extending organismal lifespan.