Neuropharmacological studies on potential therapeutical drugs and targets

Kozielewicz, Pawel (2017). Neuropharmacological studies on potential therapeutical drugs and targets. University of Birmingham. Ph.D.

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Abstract

The first project presented here was generated around 1 calcitriol (1,25D\(_3\)), and novel low-calcemic analogues (VDAs). The hypothesis of this study was that VDAs may be effective in Diffuse Large B cell Lymphoma. It has been demonstrated that 1,25D\(_3\) and certain VDAs displayed moderate cytotoxic and pro-apoptotic actions upon DLBCL cells. Additionally, 1,25D3 and VDAs used in a combination with antidepressant clomipramine displayed concentration anti-stimulatory actions upon activated normal B-cells.

The second part of the study is focused around a novel immunomodulator CX1001, data from which is currently confidential.

The third project has been built around GPR61. I have demonstrated that myc-tagged GPR61 is expressed in the cell membrane and is subject to N-glycosylation. The N12S mutant of GPR61, which is not subject to N-glycosylation, is also expressed on the cell surface. Treating the cells with tunicamycin reduces cell membrane expression of non-mutated and mutated proteins. Furthermore, GPR61 mRNA and protein are expressed in white blood cells with significantly increased level of expression of the protein in Th17 cells.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):