Four projects were selected for funding in the LEADER POB BIB 2 competition. Three of them were proposed by heads of departments at CEZAMAT WUT.

The authors of the projects are Monika Staniszewska, PhD, prof. WUT – head of the Department of Microbiology, Molecular Genetics and Genomics, Mariusz Pietrzak, PhD, prof. WUT – head of the Department of Medical Diagnostics, and Elżbieta Jastrzębska, PhD, prof. WUT – head of the Department of Medical Biotechnology.

Congratulations to the awarded authors!

source: http://badawcza.pw.edu.pl/Konkursy/Wyniki-konkursow/2024/Wyniki-konkursu-LIDER-POB-BIB-2

---

Monika Staniszewska, Biomarker diagnostics for sarcomas in stratifying patients and monitoring treatment outcomes – personalised medicine (ONCOTRACE)

 

The project aims to validate and commercialize a diagnostic method created by our team based on our current results (TRL 5) obtained in cooperation with clinicians from the National Institute of Oncology in Warsaw (NIO). Based on the results of liquid biopsy (free circulating DNA, ctDNA), we identified (1) biomarkers significant for various types of sarcoma (including Undifferentiated pleomorphic sarcoma, Myxofibrosarcoma, Dedifferentiated liposarcoma, Pleomorphic liposarcoma, Leiomyosarcoma, Malignant Peripheral Nerve Sheath Tumor, Synovial sarcoma, Sarcoma not otherwise specified) and (2) points of interest for anticancer therapy (oncotrace).

Our main objective within the project is to commercialize our technology as a linked one for precise and effective diagnosis, and diagnosis-to-treatment pathways, and to create better treatment pathway selection. We propose an original diagnostic technology including genetic, epigenetic, and transcriptomic profiling of sarcomas and the implementation of targeted therapy. The main goal is to commercialize a method/technology ensuring precise and effective diagnosis and treatment pathway selection. We achieved the above by determining: (1) the compatibility of biomarkers with mutations in the tumor (DNAseq and RNAseq), (2) the usefulness and confirmation of biomarkers in profiling sarcoma types, (3) the usefulness of biomarkers in assessing the effectiveness of neoadjuvant treatment in the form of radiochemotherapy (+/- hyperthermia) in terms of the risk of recurrence and/or metastases and the risk of complications in patients with sarcomas. We plan epigenetic analyses (ONT) of tumors. For validation, we will use predictive machine learning models based on Bayesian inference built in this project.

The proposed diagnostic service for personalized treatment of patients with sarcomas is unique on a global scale. We performed sarcoma profiling using molecular analyses in adult patients. Biomarkers that determine treatment efficiency and the patient’s current status (related to metastasis and treatment resistance) were assessed. We identified the most common mutations in the form of point changes and deletions/insertions/duplications in the tested gene fragments. Based on selected markers and ctDNA measurements at various stages of treatment, a predictive tool for treatment effectiveness will be created, and trained on clinical information about the course of the disease. Our method will take into account tumor heterogeneity.

We will provide an interpretation of the results to support the clinicians in implementing appropriate targeted therapy (TRL 9). The originality of our method is based on i) an original set of biomarkers ii) taking into account the heterogeneity of tumors iii) developing a model based on clinical data from many treatment control points iv) close cooperation with clinicians in the development and interpretation of the method v) transparently presenting the results by estimating the probabilities of therapy effectiveness. An additional advantage is the development of a diagnostic method based on interdisciplinary research carried out entirely within our team (sequencing, liquid biopsy, predictive model, medical interpretation). Personal diagnosis is a key to effective personalized treatment.

 

Mariusz Pietrzak, Development of a microfluidic system for a highly-sensitive immunodetection of inflammation biomarkers based on in-situ electrochemical detection

This project aims to develop a new design of microsystems in the form of cassettes manufactured using polyester foil technology for fast and highly sensitive, quantitative immunodetection of selected biomarkers of general and localized inflammation in samples of selected physiological fluids. To achieve this goal, a new design of the diagnostic cassette will be proposed, guaranteeing the highest possible sensitivity of electrochemical detection and resistance to signal interference under conditions of contact of electrodes with real samples, while maximizing the simplification of the structure and minimizing the sample transfer operations. The microfluidic system to be developed will be obtained from PET films and porous materials using laser cutting technology and bonding by low-temperature lamination. It is intended to combine attractive analytical parameters, no worse than those offered by enzyme-linked immunosorbent assays on solid substrates (ELISA), while maintaining simplicity and short implementation time in the microsystem and ease of voltammetric readout.

The works planned as part of the project will allow achieving the VI level of technological readiness, i.e. as a result of the integration of biochemical and microfluidic components and a planar voltammetric sensor, a prototype of a diagnostic cassette with a unique structure will be obtained, based on a different signal reading mechanism compared to similar solutions developed so far. The cassette prototype will be compatible with the dedicated flow control module constructed by the Applicant’s Team, enabling testing of the prototype in laboratory conditions that mimic real conditions with high fidelity.

The implementation of the project’s objectives will open the possibility of further development of technology aimed at developing a complete diagnostic system. This will allow us to achieve a leading role at the national and European levels in the design and production of fast and sensitive automated immunodiagnostic tests to detect several clinically important protein-based bioanalytes.

 

Elżbieta Jastrzębska, Endometrial model in Organ-on-a-chip system

Endometriosis is a chronic disease characterized by the presence of endometrium-like tissue outside the uterine cavity, most often in the peritoneum and on the ovaries. This disease causes chronic pain, inflammation, forms scar tissue and tissue adhesions, often leading to infertility and an increased risk of ovarian cancer. Current treatments, focus on the use of drugs for pain, hormones and surgical removal of disease focus. The microenvironment of endometriosis focus is complex with different cell types and biochemical factors involved in cell migration, inflammation and the formation of new blood vessels, complicating in vitro studies of the disease. The goal of our project is the development of new research models of the endometrium in the form of a three-dimensional (3D) and vascularized structure using Organ-on-a-chip technology.

Current in vitro cellular models do not faithfully reproduce the complexity of the structure of the endometrium, the dynamic processes within it, and the influence of surrounding tissues on its function. In endometriosis, for unclear reasons, endometrial cells migrate outside the uterine cavity, forming foci of disease that can survive, develop and undergo cyclical changes, just like the physiological endometrium. The lack of effective pharmacological treatments for endometriosis is another challenge. The developed model, which mimics the microenvironment of the endometrium in Organ-on-a-chip systems, may be an innovative tool that will be a technological solution to support research not only on the endometrium, but also to simulate the pathological state of endometriosis, study the pathomechanism of this disease and evaluate the effectiveness of potential therapeutic approaches. Undoubtedly, the proposed solution will have a significant impact on the socio-economic environment, as it will be a new approach providing the opportunity to conduct research on endometriosis, thus may affect the progress in the treatment of this disease. Finally, it may influence the improvement of patients’ health.

The project is interdisciplinary and involves cell engineering and microtechnology. The obtained results will provide valuable information on endometrial processes, the pathomechanism of endometriosis and the impact of new therapeutic approaches on the effectiveness of treatment. The obtained results will show significant cognitive potential and will be presented at international conferences and published in high-scoring journals from the upper decile.