PhD Project "Stimulation of Oxytocinergic Signaling to Suppress Extracranial Tumor Growth" (Althammer_0124) - Heidelberg University

Date: 03/02/2025

Application Deadline: 31/12/2024

The aim of this PhD project is to decipher the role of the neuropeptide oxytocin in suppressing tumor growth in three extracranial cancers, lung carcinoma, breast tumor and pancreatic tumors.

The neuropeptide oxytocin (OT) is best known for its role in birth and lactation, but modulates a myriad of different cellular and physiological processes, as well as complex social behaviors such as trust, empathy or social interaction. OT is a nine amino acid peptide produced in the hypothalamus and released either via long-range axonal projections in different brain areas, into the blood stream via the pituitary or somatodendritically within the hypothalamus. OT affects both cell proliferation and migration and exerts anti-inflammatory actions through the suppression of various cytokines. The G-protein coupled OT receptor (OTR) is expressed throughout the entire body and OTRs have been detected in virtually any tissue type and organ, making it an interesting therapeutic target. Numerous cancer types such as lung carcinoma, breast cancer or pancreatic cancer express OTRs, but the role of OTR expression within these tumors remains enigmatic. Several studies have investigated the effect of OT administration of tumor progression and suggest that OT could serve as a potential treatment of extracranial tumors. In colorectal adenocarcinoma lower levels of OT and OTR have been reported and administration of OT or viral-mediated activation of the OT system resulted in tumor progression. In mouse mammary carcinomas, activation of OTR signaling has been demonstrated to both inhibit or promote tumorigenesis. In lung carcinoma, elevated OTR expression has been linked to tumor progression and blockage of OTR signaling decreased cell proliferation. In pancreatic tumors, elevated OTR expression patterns have been reported, while robust functional and treatment studies are currently missing. In addition, OTR blockage markedly suppressed malignant mesothelioma cell growth, while application of OT inhibited the progression of human ovarian carcinoma cells both in vitro and in vivo. These mixed results highlight the critical need for a better understanding of OTR signaling in cancer and suggests that OT-based treatment approaches might depend both on the type of cancer and other factors such as epigenetic regulation, tumor model, age or sex. Thus it is tempting to speculate that a dysregulated OTR signaling cascade underlies excessive tumor progression and that restoring the normal balance either by activation or inhibition results in tumor growth suppression. However, the underlying mechanisms and intracellular signaling cascades that drive OT-mediated tumor growth suppression remain poorly understood. Furthermore, currently no data exists about potential co-application of OT and approved cancer therapeutics to potentially enhance their anti-cancer effects.

The aim of this PhD project is to decipher the role of the neuropeptide oxytocin in suppressing tumor growth in three extracranial cancers, lung carcinoma, breast tumor and pancreatic tumors. We will utilize specific oxytocin receptor agonist and antagonist in a K-ras mouse model for lung and pancreatic cancer. Additionally, oxytocin will be co-applied with existing, approved cancer drugs to evaluate potential enhancements in their efficacy. Key outcomes will include monitoring tumor growth and size as well as overall animal survival rates, providing insight into oxytocin’s therapeutic potential. Molecular assessments of tumors will be conducted post-treatment to elucidate underlying mechanisms. Complementary studies in cancer cell lines will focus on intracellular signaling pathways activated by oxytocin, aiming to delineate its role in modulating cancer cell progression. This multidisciplinary approach seeks to enhance our understanding of oxytocin as an adjunctive therapy in cancer treatment, paving the way for novel strategies targeting neuropeptide signaling in oncogenesis.

Personal qualifications:

- Proficiency in cell culture techniques, with a proven track record of hands-on experience. 
- Strong background in cancer biology or related disciplines, preferably demonstrated through a cancer-focused Master’s program or equivalent experience. 
- Prior expertise in immunohistochemistry, confocal imaging, and -omics data analysis (e.g., transcriptomics, proteomics, or metabolomics). 
- Experience with animal models is highly advantageous; a FELASA B certificate or equivalent qualification is preferred. 
- Exceptional communication and organizational skills, with the ability to manage multiple tasks and priorities effectively. 
- Self-motivated and capable of working independently while maintaining high standards of scientific rigor. 
- A collaborative and proactive team player, eager to contribute to a multidisciplinary research environment.

Please submit your application exclusively through the HBIGS application system:

https://www.hbigs.uni-heidelberg.de/main_application.html

Please read more under "Open PhD Positions" on: https://www.hbigs.uni-heidelberg.de