Our laboratory offers a dynamic research environment and we are constantly looking for motivated scientists and students to join our team. For available open positions contact Päivi M. Ojala.
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.
Laboratory Manager and research assistant
I participate in the scientific projects by providing help in various laboratory techniques for cell biology (cell culture, lentivirus, retrovirus and KSHV preparation), molecular biology (cloning, PCR, western blotting, immunostaining and fluorescent microscopy), microbiology, pathology (mouse tissue processing, paraffin embedding and sectioning).
My long-term goal is to uncover the factors that render the virus expression program so diverse in BECs and LECs. Currently, I am studying the role of PROX1, the master regulator of lymphatic cell fate, in KSHV life cycle as well as in KS tumorigenesis.
My research focuses on understanding how KSHV lytic proteins interfere with the host DNA replication to favor virus replication and spread. Furthermore, I am investigating whether the virus has evolved strategies to exploit DNA damage response for its own replication. Identification of cellular proteins crucial for productive lytic replication will help us to conduct focused screens to identify inhibitors targeting these proteins and to limit virus production and dissemination.
In addition, I am also using the recent CRISPR-interference technologies to control the expression of the KSHV genes. The goal of this project will be to utilize these tools in the gain-of-function and loss-of-function screens.
I am currently studying interactions between melanoma cells and lymphatic endothelial cells (LECs). Melanoma primarily disseminates and metastasizes to distant organs through the lymphatic vessels. Our studies have revealed that crosstalk between melanoma cells and LECs increases adhesion, invasion and tumorigenic potential of melanoma cells. My goal is to reveal the molecular mechanisms behind these changes, as provide cues for new therapeutic targets.
My project focuses on studying the effects of Prox1, the master regulator of lymphatic cell fate, in KSHV-infected cells. The goal of the research is to elucidate the regulatory role of Prox1 and interacting partners in KSHV reactivation and KSHV-induced oncogenesis and in the latent and lytic viral life cycle.
Sudar Krishnam Rajan Shanthi
Raquel Díaz Martínez