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Researcher
Jamoliddin Razzokov
- Research Expertise:Cold atmospheric plasma, generated at room temperature and atmospheric pressure, has been emerging as a potential cancer treatment strategy. It has been extensively studied in vitro and in multiple tumor models in vivo. However, research in ‘plasma oncology’ has been mainly focused on examining the sensitivity of various cancer cell types, applying different operating conditions, and paying virtually no attention to the contribution of the immune system. Recently, studies have revealed that plasma may help stimulate a patient’s anti-cancer immune response via induction of immunogenic cancer cell death (ICD). In spite of these promising results, experimental investigations in plasma-induced ICD are still in premature stages, and the precise action of plasma is still vague. Therefore, the underlying mechanisms require more fundamental investigations. In this project, I perform atomic scale computer simulations in order to precisely determine the role of plasma-generated RONS in plasma immune-oncology, by investigating the interaction mechanism of signaling proteins, which normally inhibit the cytotoxicity of the immune cells. In particular, I study the interaction mechanisms of CD47 and SIRPa proteins. In many cancer cells, CD47 is upregulated. Cancer cells use CD47 to escape from the immune system through binding with SIRPa, downregulating the cytotoxicity of the immune system. My hypothesis is that plasma treatment induces oxidative/nitrosative damage to CD47, thereby reducing the interaction between SIRPa proteins, which hopefully leads to elimination of the cancer cells by the immune cells. My simulation results will be verified with in vitro experiments performed by Dr. Lin in our group. This will provide a qualitative verification of my hypothesis that plasma-treated CD47 can form a complex with SIRPa with reduced binding affinity, inhibiting the binding to the immune cell receptors, which leads to killing of the cancer cells by the immune cells.
- Keywords:MOLECULAR DYNAMICS, Physics (incl. astronomy)
- Disciplines:Astronomy and space sciences, Atomic and molecular physics, Classical physics, Condensed matter physics and nanophysics, Elementary particle and high energy physics, Materials physics, Mathematical physics, Nuclear physics, Optical physics, Physics of gases, plasmas and electric discharges, Quantum physics, Other physical sciences, Other natural sciences
- Research techniques:I will perform non-reactive MD simulations using the GROMACS simulation package and applying GROMOS force fields. We have successfully used this package and force field parameters for amino acids (including plasma-induced oxidation products) in our previous computational studies. I will carry out umbrella sampling MD, to study the effect of oxidation on conformation and binding free energy between the above mentioned proteins. Comparison between the binding free energies of the native and oxidized cancer cell proteins (as well as the native and oxidized CD47 and SIRPa complex) with their receptors will give information on the effect of plasma oxidation on these protein complexes. This will give more insight in whether plasma oxidation causes immune cell activation or suppression against cancer cells, and to what extent, which is the overall research question of my project.
- Users of research expertise:The results of this project will facilitate the translation of plasma devices into clinics. In addition, the outcome of this project will be of interest for researchers who work in the biochemical and medicinal fields.