2024 Globalink Research Internship
The Globalink research internship will support two undergraduates/MSc students to work on the following summer project in my research group during May 2024- August 2024. One position is for the student with background in mathematics and computation, and one position for the student with background in biology and experiments.
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Project 1: Mathematical modeling and analysis for oncolytic virotherapy (OV) in cancer immunology [Project ID:33020]
In the OV, the oncolytic viruses were injected into the patients to infect cancer cells. Once the tumor cell is infected, the viruses replicate themselves inside the cancer cell and will be released into the tumor microenvironment to attract more cytotoxic T cells and macrophages to kill cancer cells resulting in tumor eradication. Therefore, the higher population of the viruses is, the better treatment efficacy of OV is. However, the population of the viruses is reduced, if the infected cancer cells are attacked by macrophages before the viruses were released. Thus, the immune checkpoints expressed on macrophages (such as CD200) reduce the functions of macrophages and hence reduce the killing rate of infected cancer cells by macrophages resulting in a higher population of viruses and a better treatment efficacy of OV. Additionally, immune checkpoint inhibitors for T cells (such as anti-PD-1) enhance the killing rate of tumor cells by T cells and hence improve the treatment efficacy of OV. Therefore, combination of overexpression of the immune checkpoint on macrophages and immune checkpoint inhibitors for T cells could obtain the optimal treatment efficacy of OV.
In this project, we will work on developing mathematical (ODE) model to capture the immune responses in the combination of overexpression of the immune checkpoint on macrophages and immune checkpoint inhibitors for T cells in the OVs. This ODEs model includes the variables: uninfected tumor cells, virus-infected tumor cells, virus particles, M1 and M2 macrophages, CD8+ T cells, CD200- CD200R, and PD-1-PD-L1 to investigate the optimal treatment efficacy of OV by using numerical simulation, sensitivity analysis, and numerical bifurcation diagram.
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Project 2: Mathematical analysis and modeling for the opposite functions of immune checkpoint inhibitors in cancer treatment [Project ID:33021]
In most of my previous works related to immune checkpoint inhibitors, we used modeling and simulation tools to investigate how the balance between the pro-inflammatory and anti-inflammatory reactions from different types of treatments affects the tumor growth/treatment outcome. The model structures or the parameter setting could be different due to different treatment targets or cancer types, but the idea is the same: the balance between pro-inflammatory and anti-inflammatory reactions.
Thus, in this project, we will generate a general mathematical model incorporating general functions f and g for the pro-inflammatory and anti-inflammatory reactions that can be used for most immune checkpoint inhibitors. Next, we will use mathematical analysis or simulation to derive conditions of the model for tumor reduction/promotion based on the function properties of f and g.
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Project 3: CAR-T cell treatment in acute and chronic B cell leukemias and then extend this model to CAR-T cell treatment in cancer treatment [Project ID:33022]
The chimeric antigen receptor (CAR) T cell therapy uses the engineering patients’ immune cells to attack the target cells. The treatment efficacy of CAR-T cell treatment in acute and chronic B cell leukemias is excellent, because the biomarkers of malignant B cells on CAR-T cell can accurate target the abnormal B cells and avoid to damage the normal and healthy cells. Recently, researchers started to apply the CAR-T cell therapy to cancers. However, the treatment outcome is not good as expected. The reason is that the biomarkers are not specific to cancer cells, such that the CAR-T cells also attack other normal cells and then cause serious side-effect of the patients. In this project, we will create a mathematical model to capture the mechanism of how the CAR-T cell works in B cell leukemias and the interaction between the biomarkers and B cells. Next, we will modify this model to capture the interaction between CAR-T cells and tumor microenvironment to investigate the potential methods for improving the treatment outcome of CAR-T cell in cancer.
If you would like to work on these summer project during 2024 summer in my group, please submit your application to the following links before the application deadline, September 22, 2023.
Information of student application: https://www.mitacs.ca/en/programs/globalink/globalink-research-internship