Marlen Metzner

As the Next Generation Sequencing Lead in the newly established Therapy Acceleration Laboratory (TAL) at the Weatherall Institute of Molecular Medicine, I am responsible for running the NGS and Molecular Section in the TAL, with the help of other members of the team. My role includes the development and validation of NGS and other molecular assays that can be used to perform genetic analyses on patient samples enrolled in national and international clinical trials testing new drugs or drug combinations for various diseases, among them Acute Myeloid leukemia. The assays we are developing include Next Generation sequencing panels of genes recurrently mutated in myeloid malignancies, which can be used for the genetic screening of patient samples at diagnosis but also for the purpose of measurable residual disease (MRD) detection at follow-up. This allows us to first define the genetic landscape of the disease at trial entry and then monitor the patient throughout treatment to assess how much disease is still present after therapy. In addition to NGS, we use other assays to detect single gene mutations or fusion genes with methodologies such as capillary electrophoresis or qPCR. Our work is helped by a high degree of automation in order to improve efficiency and reduce hands-on time and human errors. Examples include the extraction of DNA or RNA from biological samples or the preparation of NGS libraries or set-up of other molecular assays using various liquid handling robots. Apart from the implementation of genetic assays including bioinformatic data analysis, result review and reporting, I am involved in training and supervising other staff members in the molecular section and preparing documentation required for the accreditation of genetic assays.

Before moving to the TAL, I worked as a Research Assistant in Paresh Vyas’ laboratory at the Weatherall Institute of Molecular Medicine for 8 years. There I was working on a number of projects in the lab focussing on understanding the genetic heterogeneity of Acute Myeloid Leukemia (AML) and contributed to publishing scientific data. I helped set up and was routinely running a capture-based NGS sequencing panel to genetically characterise driver mutations in patient samples from the lab’s biobank as well as from large national AML clinical trials, as well as early-phase clinical trials of novel compounds and treatment combinations with the aim to better understand the impact of somatic mutations on clinical outcome and mechanisms of response and resistance to different therapies. Apart from bulk DNA and RNA sequencing techniques, we utilised single cell methods to study genetic, transcriptomic and chromatin accessibility changes at the single cell level in certain patient groups or throughout treatment. I have also been involved in setting up and providing Minimal Residual Disease (MRD) monitoring using multi-parameter flow cytometry for AML patients enrolled in clinical trials.

Prior to joining the WIMM in 2015, I studied for a B.Sc. and M.Sc. in Molecular Life Sciences at the University of Lübeck in Germany and worked on my master’s project at the Molecular Cancer Research Center of the Charite, Berlin, Germany.