With this project we aim to understand the interplay between tumor and its associated microenvironment in different stages of Prostate Cancer (PCa), and how they affect treatment response and metastatic progression. Molecular (genomic, transcriptomic and proteomic) and phenotypic characterisation of tumor and tumor microenvironment compartments in PCa patient-derived xenograft models (PDXs) and multifocal primary PCa. Heterogeneity in therapy response in PDXs from primary and advanced disease is addressed using 3D organoid culture models, with ultimate goal to implement this knowledge towards personalised, patient-derived routine test assays. To this aim, drug repurposing of FDA approved drugs for potential use in PCa is being evaluated and paralleled to specific genomic features of different tumors or multifocal tumor lesions in primary PCa stage.
Dr Sofia Karkampouna, PhD
We aim to investigate the molecular and functional characteristics of highly metastatic and oncogenic prostate cancer stem/progenitor-like cells. In particular, we are interested in identifying targetable molecules and metabolic pathways altered during prostate cancer progression and bone metastasis formation. The final goal will be to identify novel biomarkers that could provide a better stratification and effective treatment for prostate cancer patients.We work in close collaboration with the Clinical Department of Urology to implement a personalized medicine approach that can translate our findings into the clinic.
Dr. Eugenio Zoni, PhD
Short description project in development
Dr. Marta de Menna, PhD
Dr. Katja Ovinnikova, PhD
We aim to employ advanced in vitro models of the alveoli - the site of most severe COVID-19 manifestation - to study how SARS-CoV-2 infection abrogates normal cell function. These insights might enable the identification of promising candidate proteins for therapeutic targeting in severe cases of COVID-19.
Dr. Mirjam Kiener, PhD
Prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer-related male death. Currently, markers fail in providing an effective patient stratification. Lethal cases receive new therapies once they have failed local and hormonal treatment. The mammalian macromolecular complex, as CTLH E3-ubiquitin ligase, characterized by well conserved CTLH domain showing an ubiquitin ligase activity increasing cell radiosensitivity in prostate cancer. This suggests that the CTLH Complex, through its main protein RanBP9, is potentially involved in the PCa tumorigenesis. The aim of this project is to investigate the role of RanBP9 in PCa progression and to address the basis for a novel therapy response prediction.
Dr. Mario Scarpa, PhD
Bone metastasis of prostate cancer indicates that, unfortunately, the disease will most likely not be eradicated: while different clinical options are available to address bone-related symptoms, a definitive cure for bone-metastatic prostate cancer is still missing. This research project develop from this background and is directed towards the generation of versatile in vitro models to study the interactions of cancer cells with bone cells and cells of the immune system.
Federica La Manna, MSc.
Bladder cancer (BLCa) is the 5th most common cancer in the world and the costliest cancer to treat on a per patient basis. Muscle bladder cancer (MIBC) is a highly aggressive disease, to which about half of the patients succumb within 5 years after diagnosis. MIBC is highly heterogeneous and clinical guidelines offer cisplatin-based neoadjuvant chemotherapy (NAC) to all patients. Despite NAC, 45% of patients die within 5 years and 60% due to lack in response. The mechanisms of resistance of MIBC to systemic treatment are largely unknown. Moreover, models for the personalized investigation of drug response and strategies for co-targeting do not exist. Based on the expression of gene signatures MIBC can be subclassifies at least into 4 groups: Claudin-low, Basal, Luminal infiltrated Luminal tumor. Our patient derived models (Patient derived organoids (PDO), patient derived xenograft (PDX), and ex-vivo tissue slices) can be used for molecular and functional characterization of parental tumor and to test the therapeutic potential and possible responsiveness to selected drugs.
Minoli Martina, PhD Student
We aim to investigate the role of the fetal oncoprotein Cripto in primary and castration resistant PCa. Cripto is a glycosyl-phosphatidylinositol (GPI) anchored protein that regulates stem cell- associated signaling pathways and promotes cellular plasticity, epithelia to mesenchymal transition and maintenance of the stem cell state during normal development, tissue homeostasis and tumorigenesis.
Gastrointestinal stromal tumour (GIST) is a tumour of mesenchymal origin and accounts for the majority of mesenchymal tumour of gastrointestinal tract (9). Its incidence is evaluated between 7 to 15 cases per 1 million persons per year. This represent around 120 new cases per year in Switzerland, according to the Swiss GIST group (www.gist.ch). Here we aim to develop gentically engineered mouse model of GIST that can be used for preclinical drug testing as well as better understanding of the disease. We are currently optimizing the conditions for generating tumours of decent size within reasonable time so there is a window for therapeutic treatment
Saurav Sabvedi, PhD Student
We aim to further understand cancer heterogeneity and link the genomic landscape defined to the functional response of organoids derived from individual cores in terms of drug response, in order to prevent disease progression or help to solve the current treatment failures of treating PCa as a bulk.Wang Juening, PhD
Wanli, PhD Student
Exploring the role of key molecular players in putative stem cell subpopulation s of prostate cancer
With this project we aim to identify key genes in PCa stem cells which may explain the underlying biological processes and offer strategies for identification of high risk disease or new strategies for the treatment of PCa targeting residual androgen-independent clones.
Elucidating the stromal contribution of androgen deprivation therapy-resistance in prostate cancer
Francesco Bonollo, PhD Student
We will investigate the role of Cancer-Associated Fibroblasts (CAFs) in promoting castration-resistant and metastatic prostate cancer (PCa). To purse this aim, three different PCa patient-derived xenograft(PDX) models will be used, representing androgen-dependent soft tissue metastasis (PNPCa model), androgen-dependent bone metastasis (BM18) and androgen-independent bone metastasis (LAPC9).
Understanding mechanisms of bladder cancer to therapy resistance
Alexander Abey Allen, PhD Student
We aim to transcriptionally characterize patient derived organoids from different stages of bladder cancer before and after treatment.