To discover novel mechanisms of cancer development and progression, our group is studying the virus-host interactions involved in pathogenesis of Kaposi Sarcoma herpesvirus (KSHV), an oncogenic gamma-2 herpesvirus. KSHV can infect both blood and lymphatic endothelial cells (BECs and LECs, respectively), inducing a virus-specific de-differentiation program which contributes to KS tumorigenesis. Furthermore, the outcome of the infection is different in the two cell types. While in BECs KSHV establishes a latent infection with very few viral proteins expressed, in LECs, the virus displays a dysregulated/lytic expression program with spontaneous production of infectious virus. To identify new therapeutic approaches for the KSHV-associated cancers the research in the group also focuses to identify novel signaling pathways and cellular proteins critical for KSHV viral replication by functional genomics and automated high-content imaging approaches.
We are also interested in understanding the molecular circuits contributing to cancer cell metastasis, with a special focus on cancers disseminating through the lymphatic system. To this end we are investigating the interactions of cancer cells with the LECs using several co-culture cell models to mimic the cancer cell-LEC interactions in vivo.
Chimeric Antigen Receptor (CAR) T cell adoptive cell therapy has revolutionized cancer treatment with a remarkable efficacy in the treatment of B-lineage acute lymphoblastic leukemia and lymphomas in adults and children. In CAR T therapy, patient-derived T cells are isolated in the lab and genetically manipulated via viral transduction to express a CAR against a specific tumor-associated antigen (TAA). CAR T cells are then infused back into the patient and mount a tumor-directed immune response upon TAA interaction. The CAR confers both target cell recognition as well as activation of the effector T cell, thus equipping the body’s own immune system to fight effectively cancer.
Despite its efficacy in hematological malignancies, CAR T therapies have had hitherto little success in treating solid tumors. The challenges for CAR T cells against solid malignancies are associated with three key tumor features, (i) TAA heterogeneity, (ii) tumor microenvironment and, (iii) immunosuppression.
With the support of The Cancer Foundation Finland (Syöpäjärjestöt) our research aims to engineer a CAR with improved homing, trafficking and targeting against solid tumors.
My project focuses on melanoma cell crosstalk with lymphatic endothelial cells (LECs). We have demonstrated that melanoma cell communication with LECs actively promotes invasion and metastasis of melanoma cells. Currently, I am studying the prometastatic functional and molecular changes in both cell types upon this crosstalk.
To understand the cell tropism of KSHV for lymphatic endothelial cells forms the core of my project. My research focuses on the interaction of lymphatic transcription factors, Prox1 and Sox18, with various host epigenetic remodelers that regulate KSHV latent and lytic replication. This will help to elucidate the mechanisms governing the KSHV lytic and latent replication in lymphatic endothelial cells. Also, by utilizing endothelial precursor cells isolated from the blood of healthy individuals, I am developing a new KSHV-infection model for testing inhibitors of the KSHV replication in collaboration with a biotechnology company.
I performed the first part of my PhD thesis project by studying the role of the Eph-ephrin signaling pathway in high-grade serous ovarian cancer. I am currently focusing on the transcription factor SOX18. The aim of my current project is to elucidate the mechanics and functions of SOX18 signaling in gastric and ovarian cancers.
I am researching CAR T cell therapy with a focus on solid tumor treatment. The aim is to improve CAR T cells to have a better capability of reaching their target cancer cells and sustaining effector functions in the stroma rich and immunosuppressive environment.