Michiel Pegtel is currently assistant professor at the Department of Pathology in the Free University Medical Center of the Free University of Amsterdam, The Netherlands. In addition Michiel is chief scientific officer of ExBiome B.V. a small RNA diagnostics start-up company. He is heading the Exosomes Research group (ERG) a multi-disciplinary laboratory focusing on cancer biology, cancer immunology and autoimmunity. The research lines are connected by the recent realization that most cells secrete small vesicles called ‘exosomes’ that have a key role in many biological processes and can be exploited useful for clinical purposes. The research lines of the ERG fall into three categories.
1. Tumor exosomes Biology and the microenvironment. The tumor microenvironment takes part in virtually every aspect of cancer development and progression, including metastasis formation and development of resistance to therapeutics. Mesenchymal stem cells (MSCs) are established contributors to malignant dissemination in breast cancer, brain tumors, colon cancer, multiple myeloma and osteosarcoma a devastating tumor of bone tissue that affects children. MSCs are adult stem cells that can home to sites of inflammation, where in response to environmental cues they can differentiate into cancer-supporting cells. We are trying to understand this process using innovative mouse models and find ways to target the tumor-stoma to stop metastasis. To discover how tumor cells secrete exosomes we developed a unique live-imaging approach that can study tumor cell behavior at the single cells level. Finally super-resolution microscopy is used to characterize tumor exosomes heterogeneity at the single particle level.
2. Exosomes and small non-coding RNAs. We aim to unravel how small RNA sorting and transmission via exosomes in the tumor microenvironment and autoimmune disease drives chronic inflammation and therapy resistance. We have shown that 22nt microRNAs can travel between cell-types and that viruses use this ancient communication pathway to their advantage and use this knowledge to investigate mechanisms of disease. Using clinical specimens such as tissue sections and state-of-art culture methods we investigate if and how genetic information in the form of small RNAs influence are transported in human disease and study the behavior of immune cells that received genetic information from exosomes.
3. Liquid Biopsy. We aim to decipher how exosomal small RNAs in cancer patient biofluids can be optimally used for diagnosis, assessment of prognosis, early detection of disease recurrence. We wish to exploit this information as a surrogate for traditional biopsies or imaging with the purpose of predicting response to treatment and the development of resistance to therapy. To achieve this we need to study how small 22 nucleotide (micro)RNAs are stabilized and detectable in human biofluids (blood, urine and CSF), develop clever isolation methods, design new detection techniques and improve sequencing approaches that are applicable for patient biofluids.