Background and objective
A substantial number of patients fail to respond to immune checkpoint pathway blockade caused by WNT/β-catenin signaling-induced resistance. Combined treatment, using tankyrase inhibitor and anti-PD-1/immunotherapy, results in enabled immunotherapy efficacy and total eradication in a subset of treated tumors when using syngeneic mouse melanoma models.
The main aim is to bring TNKSi into clinical practice for cancer treatment, supported by in-depth analysis of the mode-of-action that rules its efficacy in combination with PD-1 immune checkpoint inhibition, as well as counteraction of resistance to checkpoint inhibition. The objective is to identify and characterize the anti-tumor factors and molecular mechanisms that are induced by tankyrase inhibitors in an immunocompetent setting: Such as cytokines, signaling pathways, immune cells as well as direct effects on both tumors cells and host.
The figure shows synergistic effects of the tankyase inhibitor G007-LK and the checkpoint
inhibitor anti-PD-1 in a syngeneic/immunocompetent mouse melanoma model (left/middle). The current model for mechanism of action is shown (right).
Possible methods and techniques
Cell culture and growth assays, immunoassays/ELISA, real-time qRT-PCR, siRNA technology, immunofluorescence/immunohistochemistry/microscopy, flow cytometry, Western blotting, immune cell chemotaxis assay, CRISPR-Cas9 gene knock-out, investigate induced chemokine secretion in a panel of human melanoma cells. If in vitro findings need in vivo validation we will use mouse cancer models.
What we offer the student
- The student will be included as a part of Jo Waaler’s research group
- We offer 1-2 Master theses/projects that eventually will be tailor-made after a discussion with the student, that also will contain information regarding lab safety, law and ethical aspects (a HMS form will be submitted together with the student)
- Office space and laboratory space (at the new Domus Medica building)
- The supervisor/student will discuss strategy and credit for work that aim to reach the quality for publication in international peer reviewed journals.
- An international and ambitious research group that can strongly support you on the way to an independent research career and Ph.D in biology
- Training in both basic and cutting edge techniques in cancer/cell biology, molecular biology as well as mouse animal models
- The group has broad experience in cell biology, molecular biology, biochemistry methods and statistics: Cell culture and growth assays, luciferase reporter-assays, immunoassays/ELISA, real-time qRT-PCR, RNA-sequencing, immunofluorescence and immunohistochemistry, microscopy, flow cytometry, Western blotting, PCR, cloning, CRISPR-Cas9 technology, bioinformatics, stem cell technology, organ-on-chip technology and mouse cancer models
- Training in dissemination skills: Presentations, writing, project planning
- We are an international research team with researchers at different ages and stages of their careers
- We have weekly lab meetings/journal clubs, the research team share their expertise and support you in finding relevant literature
- Regular social events including summer and Christmas parties as well as group retreats.
What we expect from you
- The student must stay faithful to the project plan, follow to ethical and institute guidelines and make sure, together with the supervisor, that deadlines are kept.
- A highly motivated, proactive and curious candidate who would like to work in an internationally competitive laboratory
- A full-time student that you plan your own time
- Read relevant literature and spend extensive time to understand the project
- That you become close to an independent laboratorial worker after the training period (1-2 months), but importantly know when to ask for help
- You should also present your work in internal presentations to practice for your final examination.
Supervisor for this project and the research group
Jo Waaler will be the supervisor for this project. He is a group leader and researcher (Oslo University Hospital-Rikshospitalet) and is also associated with the cross-disciplinary “center of excellence” Hybrid Technology Hub (SFF-HTH, director Professor Stefan Krauss [website].
Jo Waaler has functioned as a supervisor for 8 master students.
For questions and more information, please contact Jo Waaler at jo.waaler@rr-research.no, by phone (951 48 669) or visit me at room L-209/2nd floor at Domus Medica (new building). For more detailed information on the projects and the lab, please see Waalergruppen.