Senada Koljenovic professor

Research Senada Koljenovic

Research team

Expertise

Pathologist-PI with main interest inHead and Neck pathology and Dermatopathology. Research to improve the surgical-pathological communication and correlation of information for better diagnosis, surgical results and patient outcome. International multidisciplinary research network to facilitate design and conduction of multi-center studies. Translational research with focus on applications of Raman spectroscopy-based tools in Head and Neck surgery (Raman-guided surgical resections facilitating safe surgical margins in oral cancer) and in characterisation of pre-neoplasia for its’s early diagnosis. Research on histological, clinical and molecular aspects of pre-neoplasia by conducting an extensive study on histological diagnosis (and classification) of pre-neoplasia in head and neck region and other sites (e.g. vulva). This investigation also involves exploring the potential role of immunohistochemical markers in aiding the diagnosis. Translation research with focus on the diagnosis of ambiguous melanocytic skin lesions by whole genome copy number analysis.

Innovative cell death diagnostics allowing stratifying critically ill patients for novel ferroptosis or pyroptosis intervention strategies 01/01/2023 - 31/12/2026

Abstract

The complexity of critical illness in intensive care essentially requires a precision approach. Organ failure and sepsis are key detrimental factors in critical illness, and fundamentally driven by an auto-amplifying loop of cell death and inflammation. This process feeds dynamic disease fluctuations and heterogeneity in critical care, which might partially explain inconsistent translatability. Patients with similar clinical presentations typically have different cellular and molecular responses due to individual differences and co- morbidities. To deal with this form of heterogeneity, innovative biomarkers with predictive value are needed to allow determining subtypes of clinically similar patients. There is a growing list of circulating detrimental biomolecules related to some forms of regulated non-apopoptic cell death (i.e. so-called ferroptotic and pyroptotic cell death), which are druggable and allow stratifying critically ill patients. Actually, we discovered that therapeutic targeting ferroptosis or pyroptosis respectively increased survival in experimental models of multi organ failure or septic shock. To allow follow-up of clinical intervention studies, real-time diagnostics for these detrimental factors are needed. Dynamic monitoring of a panel of cytokines in critically ill patients showed prognostic value for 30-day survival, septic shock and organ injury. To level up our proof of concept, we want to conduct a translational study in critically ill patients by using real-time immunodiagnostics to detect ferroptosis and pyroptosis; which should allow quick stratification for the linked targeted therapies thereby preventing organ/systemic dysfunction and mortality. To detect general tissue injury due to excess cell death, we also optimized a procedure to episequence plasma cell free DNA (cfDNA) using real-time Oxford Nanopore Technology. As a potential future complementary diagnostic tool, we want to determine the diagnostic power of nanopore episequencing to detect tissue specific cell death. To process the clinical and molecular fingerprint of the critically ill determined in biofluids, we additionally use big data mining approaches in these phenotypically well-characterized patients. Precision intervention based on innovative real-time molecular diagnostics and stratification could bring diagnostics in intensive care into the 21st century and pinpoint which patients are likely to benefit from a certain treatment.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

A new photoelectrochemical singlet oxygen-based detection platform for a panel of cancer biomarkers in tissue and liquid biopsies (SOCAN). 01/01/2023 - 31/12/2026

Abstract

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. SOCan will contribute to the (early) diagnosis and follow up of cancer via a new disruptive detection platform, i.e. singlet oxygen-based photoelectrochemical detection of cancer biomarkers. Those biomarkers are increasingly discovered and validated, but the detection necessitates rapid, accurate and sensitive devices. To achieve this, the combined use of electrochemical detection with light-triggered sensor technology for the specific and sensitive detection of pre-selected DNA and RNA cancer biomarkers is proposed. The application of this technology on tissue and liquid biopsy samples will be a major contribution to the early detection of cancer. SOCan aligns with the EU Mission on Cancer and will lead to an affordable and sensitive diagnosis of cancer, reducing the time to result which allows faster and specific treatment, and thereby saving lives.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Detection and quantification of a panel of clinically relevant DNA biomarker sequences containing KRAS mutations in tissue and liquid biopsies via a novel photoelectrochemical technology. 01/01/2023 - 31/12/2024

Abstract

Inspired by the mission of the EU commission, this project commits to tackle a major societal challenge, i.e. fighting cancer. A striking target for 2030 has been set by the EU: more than 3 million lives saved, living longer and better, achieve a thorough understanding of cancer, prevent what is preventable, optimize diagnosis and treatment, support the quality of life of all people exposed to cancer, and ensure equitable access to the above across Europe. This project contributes to (early) diagnosis and follow up of the disease. More and more biomarkers are discovered and validated for cancer and the highly precise determination thereof is high on the priority list, necessitating analytical devices that allow rapid and accurate analysis with high sensitivity. Electrochemical biochips are an emerging tool for point-of-care diagnostic systems due to their inherent high sensitivity and cost and time effectiveness. We propose the combined use of electrochemical detection with a light-triggered sensing technology for the specific and selective photoelectrochemical detection of low concentrations of cancer biomarkers (i.e. KRAS mutations), also allowing us to detect a panel of cancer biomarkers. Detection and quantification of the selected target sequences will be performed in tissue and liquid biopsies, to ensure the translation from a lab technology to a device for clinicians and even patients.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Prediction of malignant potential of Ambiguous MELanocytic skin lesions by whole genome copy number Analysis: a multicenter study (AMELA). 01/10/2022 - 30/09/2026

Abstract

Melanocytic skin lesions can either be benign or malignant. Although pathologic examination often provides a final diagnosis, in a number of cases the morphology is ambiguous and the malignant potential of the lesion cannot be determined. This uncertainty of the diagnosis has important consequences for the patients and the community. In case patients are incorrectly diagnosed with melanoma instead of a benign lesion, they will be subjected to unnecessary clinical examinations, psychological pressure and social disadvantages. On the other hand, patients with an incorrect diagnosis of a benign lesion instead of melanoma are insufficiently treated leading to a high risk of developing deadly metastatic disease. In this project we aim to technically verify and clinically validate a molecular assay to predict the malignant potential of ambiguous melanocytic lesions for which proof-of-concept has ready been established. This assay is based on genome-wide copy number variation (CNV) analysis. In a first phase we will finetune and standardize the proof-of-concept assay using a training set of 106 cases, enriched with ambiguous cases. The diagnostic accuracy and ideal cut-off will be determined and the performance of the assay will be verified in an independent test set of 76 ambiguous cases. The resulting assay, hereafter named AMELA assay (assay for Ambiguous MELanocytic skin lesions Analysis), will be validated in the second phase of the study. In a second phase a prospective, observational multicenter study will be conducted. Samples of 552 patients with ambiguous lesions will be included. The clinical performance (accuracy, sensitivity and specificity) of the assay will be determined based on adverse events during 2 years of follow-up. In addition, the robustness of the assay and the potential financial impact on the society will be assessed

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Multiplexed photoelectrochemical detection technology for molecular cancer biomarkers (MultiSens). 01/01/2023 - 31/12/2023

Abstract

Inspired by the mission of the EU commission, this project commits to tackle a major societal challenge, i.e. fighting cancer. A striking target for 2030 has been set by the EU: more than 3 million lives saved, living longer and better, achieve a thorough understanding of cancer, prevent what is preventable, optimise diagnosis and treatment, support the quality of life of all people exposed to cancer, and ensure equitable access to the above across Europe. This project contributes to (early) diagnosis and follow up of the disease. More and more biomarkers are discovered and validated for cancer and the highly precise determination thereof is high on the priority list, necessitating analytical devices that allow rapid and accurate analysis with high sensitivity. Electrochemical biochips are an emerging tool for point-of-care diagnostic systems due to their inherent high sensitivity and cost and time effectiveness. We propose the combined use of electrochemical detection with a light-triggered sensing technology for the specific and selective photoelectrochemical detection of low concentrations of cancer biomarkers (i.e. KRAS mutations). In this project we will focus on the development of a multiplexed 96-well plate-based detection of a panel of cancer biomarkers. Detection and quantification of the selected target sequences will be performed in liquid biopsies, to ensure the translation from a lab technology to a device for clinicians and even patients.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project