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.
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 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.
My PhD project focuses on chimeric antigen receptor (CAR) T cell therapy. Although CAR T cell therapy has revolutionized the treatment of relapsed or refractory (R/R) B cell lymphomas, approximately half of the patients do not achieve long-term remission and many encounter severe toxicities. My project involves studying R/R B cell lymphoma patients who have received anti-CD19 CAR T cell therapy to uncover how host responses are linked to disease outcomes. In addition, my project includes translational in vitro studies that aim to improve the CAR T cell treatment efficacy by removing the effect of tumour-promoting macrophages in the lymphoma tumour microenvironment.
My PhD project focuses on how developmental transcription factors influence the biology of KSHV infection. We have identified SOX18 and PROX1 as lymphatic endothelial cell (LEC)‑specific factors that engage host epigenetic machinery to support viral maintenance. Ongoing work explores how blocking SOX18 reshapes host gene and protein expression, and how PROX1’s interactions with host chromatin modifiers regulate the balance between latency and lytic replication.