Blog with our Expert - Jürg Schwaller
Author: Martina Konantz
Meet our Expert Jürg Schwaller from the Childhood Leukemia Laboratory at the Department of Biomedicine. One of his main areas of interest is understanding the cellular and molecular mechanisms of acute myeloid leukemia (AML), a rare but highly aggressive form of blood cancer. His work focuses on developing better disease models and identifying key molecular targets to support more effective, combination-based treatment strategies. Today, he discusses his research and perspective on advancing AML treatment strategies.
Jürg Schwaller was born in Solothurn and studied medicine at the University of Bern. After graduating in 1990, he worked as a fellow in clinical pathology at the University of Zurich. Fascinated by molecular medicine, he moved back to Bern as a research fellow in Experimental Hematology-Oncology before moving in 1996 to Harvard Medical School in Boston, where he developed mouse models of acute leukemia. After nearly four years abroad, he returned to Switzerland, where he led a laboratory for clinical molecular pathology at the University of Geneva, analyzing clinical samples and performing more translational research on hematological malignancies. Since 2004, he has been heading a research group at the Department of Biomedicine of the University of Basel and the University Children's Hospital Basel, focusing on the mechanisms of childhood leukemia. His work has received several awards including the SWISS BRIDGE Award for cancer research. Jürg is not only an accomplished scientist but also a dedicated mentor who genuinely enjoys sharing his knowledge with his own students, postdocs, and colleagues. He lives in Bottmingen and enjoys traveling, music, art, and wine.
What is your personal vision of the direction of your field of research? In other words, why is it relevant and what are your main long-term goals?
Our research aims to better understand the cellular and molecular mechanisms of acute myeloid leukemia (AML), a rather rare but highly aggressive form of blood cancer. Despite some significant progress for particular forms, many paediatric but also particularly older adult AML patients that cannot undergo bone marrow or stem cell transplantation face a poor prognosis. Intensive efforts in clinic as well as in the lab strongly indicate that successful AML therapy will most likely be a combinatorial approach using small molecules that target critical pathways in the tumor cells and their interaction with the microenvironment in combination with various immunological strategies. To establish these strategies, we need models that appropriately phenocopy the disease; and we need to functionally dissect critical hubs in a network of AML-maintaining signals. Our work is focused on AML forms that are driven by particular genetic lesions, and that frequently relapse or are primary therapy-resistant. We believe that by providing improved experimental platforms and/or identifying critical cellular and/or molecular targets, we are able to contribute to the long-term goal of making AML a potentially curable disease for all patients.
Thinking about this vision: which are your main contributions to the field
Our group has developed several models that closely phenocopy the human disease. One of these, an inducible transgenic line called “iMLL-AF9” is currently used by over ten research groups worldwide: several collaborative projects are currently running and first reports are in the pipeline. This particular model allowed us to demonstrate that the cell-of-origin determines the disease not only in this model but also in human patients. In another model we have shown that a particular genetic lesion called “ETO2-GLIS2” is the driver of a highly aggressive AML form that almost exclusively affects pediatric patients. More recently, we provided proof of concept that a different genetic lesion called “NFIA-ETO2” can initiate a rare AML subtype known as acute erythroleukemia. We got in contact with this very rare but mostly incurable subtype when characterizing an unexpected phenotype that we observe in a line upon genetic inactivation of a gene encoding for a chromatin-modifying enzyme. We later molecularly and cellularly characterized a cohort of erythroleukemia patient samples collected from all over the world. Although never planned, we have still some activities on acute erythroleukemia, a field that appears not intensively studied.
What are the main challenges in your field of research?
The main challenge is the nature of the disease. In other words, although overall rare, the disease is very heterogeneous with clear genetic and biological differences between different types of AML. Today one particular AML form called “APL” can be cured in the majority of patients by targeted interference with a particular oncogene that drives this disease. Despite the hope that this principle could be successfully applied for other AML forms, up to now, we are still waiting for this breakthrough. In addition, developing a therapy for subtypes of a disease that is already rare is particularly challenging for multiple reasons, including the often limited interest by pharmaceutical companies. Therefore, there are intensive research efforts to develop strategies that could be effective for many if not for all AML subtypes. Hereby combination of different immunological strategies including checkpoint inhibitors, monoclonal antibodies, dendritic cell vaccines and T and NK based cell therapies are currently intensively studied. Some of these approaches show promising results in AML models, the clinical breakthrough is however still lacking.
What part of your work as a group leader do you enjoy/appreciate the most?
I have to admit that I really appreciate those times when I can escape the office and do some more practical work. During these moments, I might clone a particular vector, do some tissue culture experiments or analyze histology from our models under the microscope! The latter is linked to the fact that I wanted initially to become a pathologist, a field in which I spent almost 2 years. As a more “group leader-related activity”, I also like in-depth scientific discussions at meetings with collaborators of which some have become friends over the years.
The main challenge is the nature of the disease.
Jürg Schwaller
Last but not least? If we could grant you a scientific “wish”, apart from enough resources to perform your research, what would that be? The sky is the limit...
The sky is the limit? Well, then I would make it possible that the research and clinical community in my field establishes a database that contains epi/genomic (deep sequencing) information as well as clinical history from an “unlimited” number of patients with leukemic disorders collected worldwide that everyone can access. In parallel one should store primary (or transplant amplified) tumor cells taken at diagnosis and/or relapse from the same patients. All would be freely accessible for all interested researchers around the globe! In addition, with unlimited resources and enough space, I would focus on developing AML models that phenocopy the epigenomic dynamics of the disease, incorporating the regulation of multiple cooperating transgenes within specific temporal and spatial framworks. I am fully convinced that these two cornerstones would really facilitate the development of novel therapeutic breakthroughs for AML— and most likely other forms of leukemia as well.