Allam group  Prof. Dr. phil. nat. Ramanjaneyulu Allam

Our previous investigations have unveiled a crucial function of Ribonuclease inhibitor (RNH1) in regulating homeostatic hematopoiesis. In the absence of RNH1, the balance in hematopoiesis was skewed significantly to favour myelopoiesis at the expense of lymphoid and erythroid lineage cells. It has also been observed from our in-vivo mice studies that the increase in myelopoiesis however, did not culminate in a leukemic transformation. 

The ongoing project is aimed at elucidating the mechanism behind the RNH1 mediated exacerbation of myelopoiesis under homeostatic conditions and the implications of genetically modifying RNH1 expression in myeloid malignancies. For this, we are utilizing AML in-vitro (cell lines) and in-vivo (mouse) models along with AML patient derived cells. 

Our research so far has highlighted an involvement of RNH1 in the AML pathophysiology and ongoing studies are attempted at discerning a therapeutic potential of targeting RNH1 in myeloid malignancies.

Gourni group  PD Dr. Eleni Gourni

Tumors develop within a complex microenvironment consisted of diverse cell types surrounded by a matrix rich of proteins, termed tumor stroma. Stroma includes immune cells, fibroblasts and vascular enothelial cells. 

Cancer cells rely on extensive support from the stroma to survive, proliferate and invade, thus making stroma an important potential target for anti-cancer therapy. Targeting elements of stroma, may be a useful therapeutic strategy to prevent tumor growth and progression. One of those elements is the fibroblast activation protein (FAP) which is overexpressed on activated fibroblasts on several tumors types. 

The current project aims at designing and evaluating novel FAP-specific inhibitors for the generation of radiotracers with the potential to be used for the diagnosis and treatment of FAP-positive tumors. The novel radiotracers are thoroughly investigated in vitro and in vivo using cell lines and xenografted tumor models to understand their binding properties and their in vivo performance.

Konstantinidou group PD. Dr. Georgia Konstantinidou, PhD

Lung cancer is the most common cause of cancer-related deaths worldwide. Tumor-associated mutations of KRAS occur in approximately 30% of non-small cell lung cancer, the most common form of lung cancer. 

KRAS mutations are associated with aggressive, metastatic, and treatment-resistant cancers in both humans and mouse models. Mutant KRAS drives a complex network of lipid metabolic rearrangements to help cancer cells adapt to hypoxia and ensure their survival. 

We plan to determine the transcriptomic and lipidomic changes that occur in lung tumors during cancer progression and therapy resistance and assess their functional significance, accounting for tumor-to-tumor heterogeneity while preserving the spatial organization of cancer cell populations within the tumor microenvironment.

Medová Group PD Dr. med. Michaela Medová

Tyrosine kinase receptors activate a wide range of different cellular signaling pathways. Physiologically, intact signaling via the MET receptor is indispensable in embryonic development and tissue homeostasis. At the same time, MET dysregulation promotes features clearly associated with tumor growth and progression such as uncontrolled proliferation, angiogenesis, local invasion, and systemic dissemination. 

Accumulating data suggest that MET signaling may also protect tumor cells from DNA damage, hence relating its aberrant activity to resistance to DNA-damaging agents routinely used in cancer treatment. 

We have identified a previously unreported phosphorylation site on MET, which can be recognized by DNA damage master kinases and is involved not only in cellular responses towards DNA damage, but also in metastatic processes, cancer cell migration, and anchorage-independent growth. 

This project aims at dissecting the nature, function, and regulation of this phosphorylation site in oncogenic signaling of the receptor.

Meyer group  Prof. Dr. med. Sara C. Meyer

Myeloproliferative neoplasms (MPN) are chronic leukemias characterized by constitutive activation of JAK2 tyrosine kinase signaling. Clinical JAK2 inhibitors bring benefits for patients, but have limited disease-modifying activity. Allogeneic hematopoietic cell transplantation is the only curative treatment to date. 

The Meyer lab has a specific interest in the oncogenic signaling driving MPN. We have demonstrated that activation of the MAPK pathway with MEK1/2 and ERK1/2 kinases, which is involved in several cancers, limits JAK2 inhibitor therapy and needs to be adressed to enhance efficacy (Stivala, JCI 2019; Brkic, Leukemia 2021). These findings have translated to a clinical study (Adore, NCT04097821). 

Our lab is investigating mechanisms of resistance, which mediate loss of response to clinical JAK2 inhibitors, and approaches to overcome resistance. Notably, we are involved in the characterization of novel types of JAK2 inhibitors incl. type II JAK2 inhibitors currently in development towards clinical studies (Meyer, Cancer Cell 2015; Codilupi, CCR 2024).

Pabst & Seipel group  Prof. Dr. med. Thomas Pabst, PD Dr. Katja Seipel

Starting in 2020 CAR T-cell therapy has been applied in R/R B-cell lymphoma at Inselspital Bern. Biomarkers of response were evaluated in retrospective analysis in order to predict treatment outcome and improve CAR-T cell therapy.

Pandey group  Prof. Dr. phil. Amit V. Pandey

Castration-resistant prostate cancer (CRPC) represents a lethal stage of the disease, primarily driven by the tumor's ability to overcome therapy through the synthesis of its own androgens. 

Our research has advanced beyond studying single enzymes to investigate their higher-order organization into what we term "metabolic supercomplexes" or "metabolons." 

Our central hypothesis is that key enzymes in androgen production, such as CYP17A1, AKR1C3, and STS, do not function in isolation. Instead, they form organized, multi-protein complexes at the interface of cellular compartments, like the endoplasmic reticulum and the cytosol. These supercomplexes act as hyper-efficient production lines, utilizing a mechanism called "substrate channeling" to rapidly convert precursors into potent androgens that fuel cancer growth. 

This model provides a powerful new explanation for the robust resistance observed against drugs like abiraterone. Our current work focuses on characterizing the structure and function of these supercomplexes. The ultimate goal is to develop innovative therapeutic strategies that not only inhibit key enzymes but also disrupt the crucial protein-protein interactions that hold these metabolic machines together, potentially using novel small molecules or advanced nanoparticle-based delivery systems.