Development of a novel human in vitro lab on a chip system for cancer neuroscience studies
Supervisors: Dr. Mihaly Balogh ( email@example.com ), Prof. Reinoud Gosens
Starting date: based on discussion (academic year 2022/2023)
There is continuously growing attention on the less understood interplay between cancers and the nervous system, including peripheral neurons (a new emerging scientific field: “cancer neuroscience”). As an apparent example, clear evidence shows shared systemic processes involved in both the development of cancer and neuropathic pain. In addition to their roles in tumor growth, some of the chemokines (e.g. complement 5 (C5), or the CXCR3 receptor, and its ligand CXCL10) also play important roles in the development of neuropathic pain, including chemotherapy-induced peripheral neuropathy (CIPN). Despite these observations, very few studies have investigated sensory neuronal dysfunction directly induced or influenced by tumor growth or how the tumor induced alterations might influence neurons.
We have already shown – for the first time in an in vivo preclinical setting – that the development of colon cancer indeed leads to significant systemic sensory neuronal dysfunction in mice. These alterations include a significant decrease in the epidermal nerve fiber density of mice, in addition to mitochondrial dysfunction and altered Ca 2+ -homeostasis in the dorsal root ganglia of tumor bearing animals. These changes interestingly also underlie symptoms of CIPN. That is, colon cancer development seems to be leading to similar neuronal damage as in the case of CIPN, even without introducing any form of chemotherapeutic treatment. These observations seem to be extremely important for future studies aiming to determine risk factors of severe CIPN development (develops in about 30% of colon cancer patients).
The main aim of the project is to develop a fully new, completely human in vitro lab on a chip system to investigate the direct neuronal-cancer interactions.
Human pluripotent stem cells will be developed into sensory neuronal cells and co-cultured with human colorectal cancer cells by the utilization of our novel two-compartment lab on a chip system. The candidate would directly investigate the effects of human, HCT-116 colon cancer cells (and their released mediators) on neuronal growth and functions (e.g. axon growth) and also how the tumor growth is altered by the presence of neuronal mediators.
By the end of the proposed project, the candidate has successfully contributed to the development of a novel in vitro system for cancer neuroscience studies.
|Last modified:||15 July 2022 1.46 p.m.|