Fellows and alumni

ETH Host: Prof. Dr. Andrew deMello, D-CHAB
Clinical Supervisor: Prof. Dr. Michael Weller, Dr. Dr. Tobias Weiss, University Hospital Zurich

Detection of cancer in blood holds tremendous potential to improve patient care. A non-invasive biomarker for brain cancer patients that accurately reflects tumor status throughout the course of the disease is a major unmet need in cancer diagnostics. Extracellular vesicles (EVs) are a promising solution to fill this gap given their abundance in circulation and resemblance to the composition of the cell of origin.

In this project, we develop a novel liquid biopsy platform based on a microfluidic device that isolates and quantifies tumor-specific extracellular vesicles (tu-EVs). We will quantify tu-EVs in the blood of brain cancer patients with malignant brain tumors both at the initial diagnosis and throughout the disease progression. Our approach goes beyond mere detection, as we intend to integrate the obtained data with clinical parameters (time to progression, overall survival, imaging data and histopathological features) to develop a risk classification pipeline for disease recurrence as well as a monitoring tool that improves patient surveillance during treatment.

This has the potential to bridge the gap in brain cancer diagnostics by providing a blood-based biomarker, a much-needed resource in this field.

ETH Host: Prof. Dr. Dagmar Iber, D-BSSE
Clinical Supervisor: Prof. Dr. med. Christian De Geyter, University Hospital Basel

Assisted Reproductive Technology (ART) plays a pivotal role in treating infertility. Hormonal hyperstimulation of the ovaries is essential to procure an adequate number of eggs, yet the process is complex and success rates exhibit significant variability.

In this project, a computational personalized medicine approach will be further developed to personalize treatment protocols, and thereby reduce the burden during ovarian hyperstimulation and improve the outcome of ART. The algorithm based on mechanistic mathematical modelling and quantitative patient data will be tested and refined for clinical use.

The results will be used to prepare for a future randomized clinical study to compare computational personalized medicine with the conventional approach in ovarian hyperstimulation.

ETH Host: Prof. Dr. Jess Snedeker, D-HEST
Clinical Supervisor: Prof. Dr. Mazda Farshad, Balgrist University Hospital

Spinal fusion aims to stiffen instable spine segments and is currently considered the most effective treatment for degenerative spinal conditions that cause segmental instability. However, spinal fusion still carries a significant risk of failure and complications, such as adjacent segment degeneration, screw loosening, pseudarthrosis or implant failure.

Therefore, a new treatment modality called ¡°vertebropexy¡± was recently developed by Farshad et al. The goal is to achieve targeted stabilization of the spine by inserting ligamentous allografts to counteract instability in clinically relevant directions, without immobilizing the segment. To become a broadly accepted surgical alternative, the new technique must restore the original stability; provide superior long-term results; show a high cost-effectiveness and be applicable fully predictable, easy, and safely. The latter is the primary aim of this biomechanical project: Stabilization will be implemented by augmented ligamentous human donor allografts, which are attached to the bony spine with different devices that should provide optimal ligament tension. Based on these research findings, artificial ligaments might be developed to further refine this technique in the future.

ETH Host: Prof. Dr. Roger Schibli, PD. Dr. Cristina M¨¹ller, D-CHAB
Clinical Supervisor: Prof. Dr. Ali Afshar-Oromieh and Prof. Dr. Axel O. Rominger, Dept. of Nuclear Medicine, University Hospital of Bern (Inselspital)

Targeted radionuclide therapy delivers ionizing radiation to tumor cells through the accumulation of intravenously injected radiopharmaceuticals. In the case of metastatic castration-resistant prostate cancer, the currently used agent [¹⁷⁷Lu]Lu-PSMA-617 is limited by side effects from the accumulation of radioligand in non-tumor tissues and the moderate biological efficacy of ¹⁷⁷Lu. To address these shortcomings, [¹⁶¹Tb]Tb-SibuDAB was developed at ETH Z¨¹rich/Paul Scherrer Institute.

As part of a toxicity trial, we assessed the impact of [¹⁶¹Tb]Tb-SibuDAB on the overall wellbeing of the animals, as well as organ and bone marrow function. Our trial showed no substantial toxicity at realistic doses. At elevated doses, we found reduced production of thrombocytes, however the declines witnessed were clinically insignificant, suggesting a reasonable safety profile.

Furthermore, we analysed data from a clinical trial of a previous version - [¹⁷⁷Lu]Lu-SibuDAB - demonstrating dosimetry estimates compare favorably to currently marketed alternatives targeting the same enzyme. We found similar response rates and survival to currently marketed compounds despite extensive pretreatment and advanced disease stage of the study participants, demonstrating promise for further commercial development. Assessing safety signals, we showed only a minor proportion of patients develop clinically irrelevant changes in blood cell levels, curiously also related to the number of thrombocytes produced by the bone marrow.

Lastly, we made efforts towards implementing more realistic animal models of metastatic disease with reduced lesion size, drawing on previous experience demonstrating that microscopic cancer lesions are ultimately responsible for the majority of treatment failures.

ETH Host: Prof. Dr. Ferdinand von Meyenn, D-HEST
Clinical Supervisor: PD Dr. Matthias Betz, Dept. of Endocrinology, Diabetes and Metabolism, University hospital of Basel

Brown adipose tissue (BAT) can directly dissipate energy as heat in response to cold exposure. Its presence is variable in adult humans but is clearly associated with a metabolically favorable phenotype, i.e. a reduced risk of diabetes, hypertension, dyslipidemia and vascular disease. Despite a decade of research in human BAT, it is still unclear how BAT improves metabolic health.

We hypothesize that BAT may exert a metabolic buffer function by postprandial activation. It may take up metabolically unfavorable metabolites such as glucose, free fatty acids or branched chain amino acids from the blood and thus blunt their peak plasma levels. To test this hypothesis, subjects with and without active BAT will be enrolled into a clinical study. Additionally, the cellular composition of human BAT in relation to its metabolic activity will be established. The overarching goal of this proposal is to improve our understanding of BAT physiology and to elucidate why active BAT is beneficial for cardiovascular health.

ETH Host: Prof. Dr. Niko Beerenwinkel, D-?BSSE
Clinical Supervisor: Prof. Dr. med. Thorsten Zenz, Dept. of Medical Oncology and Haematology Clinic, University Hospital Zurich

In this study, we analyzed 33 patients with aggressive lymphoma, a type of blood cancer. Blood samples were collected at various points during their treatment to detect tumor DNA released into the bloodstream, known as circulating tumor DNA (ctDNA). To verify the accuracy of our methods, we conducted experiments to determine how well we could detect genetic changes, finding that we could reliably identify mutations if they constituted more than 5% of the DNA in a sample. We screened for mutations in 184 genes commonly involved in lymphoma, enabling us to reconstruct the genetic landscape of the disease in a non-invasive way, which is crucial for assessing patient prognosis. Additionally, we examined the genetic makeup of the actual tumor tissue using whole genome sequencing and single-cell DNA sequencing. This gave us a detailed understanding of the genetic changes driving the cancer and allowed us to correlate these changes with those found in ctDNA. Through this work, we tracked significant cancer-related genetic changes in several patients over time, providing deeper insights into disease progression and showing correlations with imaging results.  

ETH Host: Prof. Dr. J?rg Goldhahn, D-HEST
Clinical Supervisor: Prof. Dr. med. Jens Eckstein, PhD, CMIO, University Hospital Basel

In this project, a set of molecular heat strain markers from qualitative sweat analysis is investigated for the first time. The project is embedded into an interdisciplinary, clinical exploration study on the physiology of the human heat strain using a novel wearable device. Once fully investigated, the detection of molecular markers in sweat may optimize and personalize heat strain monitoring, if incorporated in wearable devices. These molecular sweat markers may prevent individuals from severe health threats such as heat shock and potentially increase occupational health and productivity in the long-term. Further, those molecular sweat markers have a great potential to be implemented in a variety of medical specialties such as Endocrinology and Psychiatry later.

ETH Host: Prof. Dr. Christian Wolfrum, Institute of Food Nutrition and Health, D-HEST
Clinical Supervisor: Prof. Dr. med. Thomas Frauenfelder, Diagnostic and Interventional Radiology, University Hospital Zurich

The aim of this research project was to analyze the potential impact of white adipose tissue in thermogenesis as well as finding clinical, lab and demographic parameters which might have an impact on white adipose tissue activity.  In our big retrospective study (including >12¡¯000 PET/CT scans), we found several parameters which affect the activity of white adipose tissue: BMI, age, sex, diabetes type II and blood glucose among others. In our prospective study, there was no significant difference of white adipose tissue activity in PET/CT during cold stimulation of the patients compared to PET/CT scans with regular room temperature.

ETH Host: Prof. Dr. Sebastian Kozerke, Institute for Biomedical Engineering, D-?ITET
Clinical Supervisor: Prof. Dr. med. Robert Manka, Heart Center, University Hospital Zurich

Our project aimed at imaging cardiac metabolism in heart failure by means of dynamic nuclear polarization. The technique uses C13 labeled pyruvate that has (other than naturally occurring pyruvate) a magnetic moment and can therefore be hyperpolarized and depicted using magnetic resonance imaging. Since pyruvate is part of the human sugar metabolism, it is well tolerated and is further metabolized by aerobic or anaerobic metabolic pathways. By not only imaging pyruvate, but also its downstream metabolites, the approach allows describing the energy supply and metabolism of the diseased human heart.