In the past months six new junior group leaders joined the NKI. At the recent NKI research retreat, they introduced themselves to the whole NKI research community by presenting a short overview of the projects they are working on. Below be profile each of the new junior PIs (Top row: Tineke Lenstra, Gerben Borst, Leila Akkari. Bottom row: William Faller, Benjamin Rowland, Pia Kvistborg)
Tineke Lenstra has joined the division of Gene Regulation. She is interested in gaining a better understanding of transcription regulation in eukaryotic cells. Transcription, the process in which genes are 'read' and transcribed into RNA to eventually produce proteins, is not continuous in time. It typically happens in burst of high activity, followed by sometimes quite long periods of little or no activity. This phenomenon of 'bursting' results in variability between cells, which can influence cell fate decisions and disease progression. Lenstra wants to understand the mechanisms that govern this transcriptional bursting. For this, she uses advanced live cell and single cell microscopy techniques.
Gerben Borst is an expert in the field of radiotherapy and last year became a junior group leader within the division of Cell Biology. His research focuses on a number of new strategies to improve the efficacy of radiotherapy. It is for instance known that the outcome of the treatment of brain tumors is poorer when there is a long period in between preparatory imaging and radiotherapy planning and the treatment itself. Borst has shown that this can in part be explained by movements of the tumor due to changes of the edema surrounding it; something that needs to be taken into account. In another line of research he wants to determine whether certain properties of the tumor seen on MRI's can be linked to patient outcome. Also, in the pre-clinical setting he investigates how to optimize the use of (new and traditional) radiosensitizing drugs during radiotherapy as well as the underlying mechanisms of radioresistance.
"We are very pleased with the recruitment result, a good balance of gender, excellent young researchers with exciting research plans, and with a good mix of recruits from within the NKI, from the Netherlands and from abroad. Our recruitment procedure has been modified in the last two years to be more inclusive. And it works."
Henri van Luenen, leader of the GEP team at the NKI
Leila Akkari recently joined the division of Tumor biology & Immunology. She investigates the role of the tumor microenvironment in brain and liver tumors, with the ultimate goal of harnessing the cells composing the stroma for beneficial uses. What is the role, for instance, of the macrophages in the tumor environment? She has shown that alteration of the numbers and phenotype of these macrophages in response to radiation treatment can lead to acquired therapy resistance in gliomas. But Akkari's work also shows that these macrophages can be 're-educated' to once again become potent anti-tumor effectors. In liver cancer, Akkari is interested in understanding how genetic mutations in cancer cells shape the tumor microenvironment to the tumor's advantage.
William Faller's group forms the latest addition to the division of Molecular Genetics. He studies the role of RNA translation in cancer, with a special focus on colorectal cancer (CRC). With the help of mouse models he has shown that CRC cells require increased RNA translation in order to proliferate. And that by blocking this RNA translation, mice can be protected from the disease. He now wants to fully understand the role that RNA translation plays, in order to identify therapeutic targets and potentially develop drugs that can target this process. As another interesting part of this research, Faller also investigates specific nutrient requirements of tumors.
Benjamin Rowland is the new junior group leader who was most recently appointed; as of April 1st he has his own group within the division of Gene Regulation. He already had his own research line within another division for a number of years. Rowland is interested in highly fundamental questions concerning the way DNA is organized within the nucleus of cells. More specifically, he looks at the role of two protein complexes, called cohesin and condensin. Both these ring-shaped complexes can entrap DNA inside their ring and thus, for instance, form loops and condense chromosomes during cell division. In the coming years Rowland will focus on the mechanism by which these highly conserved complexes structure chromosomes.
Pia Kvistborg is also a new group leader within the field of cancer immunology. She works on the characterization of T cells: how T cells function, how they dysfunction in cancer, and how this can be changed with the help of therapies. Part of her work is very translational. For instance, one of her research lines aims to resolve why only about half of the melanoma patients respond to checkpoint inhibition therapy (with two combined checkpoint inhibitors). The reason for this can be tumor intrinsic, but also T-cell intrinsic. Why are the T cells still not activated? In a more fundamental line of research, Kvistborg tries to determine if all tumor neoantigens are equal or if there is a hierarchy within these T cell epitopes, and which rules may help define such a hierarchy.
By Nadine Böke (scientific communication officer) and Henri van Luenen (director of operations and GEP team leader) at NKI, Netherlands.