Knowledge about genes involved in haematological cancer diseases is important for the development of new forms of treatment. In her PhD project, Louise Berkhoudt Lassen studied the function of two cancer-relevant genes – SEPT9 and NRAS. SEPT9 (septin 9) is important for the cell division process, and Louise Berkhoudt Lassen studied its function in special genetically modified cells and mice lacking the gene. She found that septin 9 is important for a particular type of cell in the immune system – the T cell. Using a technique in which the cells are stained with fluorescent dyes, she and her colleagues discovered that it was more difficult for T cells to develop from a particular stage (the double negative stage), but that memory T cells were upregulated.

NRAS (neuroblastoma RAS viral oncogene homolog gene) is among the most potent genes associated with developing cancer. Using a special technique to control the level of NRAS expression in specific mouse tissue, Louise Berkhoudt Lassen found that a strong upregulation (25 times the control level) was the reason the mice died shortly after birth. An in-depth analysis of the mice showed that they were suffering from granulocytosis, and that there was an elevated number of T cells in the spleen. The increased population of granulocytes was largely made up of immature cells, and a reduction was also found in the number of another type of cell – the monocyte. This indicates that NRAS upregulation results in a shift in the development of monocytes and granulocytes by directing too many cells towards granulocyte development.

An analysis of the two functionally very different genes shows fatal consequences of the imbalance or absence of a single gene, which is important for the future understanding of the underlying genetic changes during the development of cancer.

Time: Wednesday 17 October at 12.00
Place: William Scharft Lecture Theatre, building 1253, room 317
Title of dissertation: Functional analysis of the proto-oncogenes septin 9 and NRAS
Contact information: Louise Berkhoudt Lassen, lbl@mb.au.dk
Members of the assessment committee: 
Professor S. E. Hilary Russell, Departments of Molecular Oncology and Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Professor Bo Porse, Finsen Laboratory, Rigshospitalet, Copenhagen
Professor Claus Oxvig (chair), Department of Molecular Biology and Genetics, Aarhus University
Main supervisor:
Associate Professor Ernst-Martin Füchtbauer, Department of Molecular Biology and Genetics, Aarhus University
Language: The dissertation will be defended in English

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1521, room 112, 8000 Aarhus C.