ORCID Profile
0000-0002-0545-4357
Current Organisation
BRAC University
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Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.CHEMBIOL.2021.10.004
Abstract: Harnessing the immunomodulatory activity of cytokines is a focus of therapies targeting inflammatory disease. The interleukin (IL)-1 superfamily contains pro-inflammatory and anti-inflammatory members that help orchestrate the immune response in adaptive and innate immunity. Of these molecules, IL-37 has robust anti-inflammatory activity across a range of disease models through inhibition of pro-inflammatory signaling cascades downstream of tumor necrosis factor, IL-1, and toll-like receptor pathways. We find that IL-37 is unstable with a poor pharmacokinetic and manufacturing profile. Here, we present the engineering of IL-37 from an unstable cytokine into an anti-inflammatory molecule with an excellent therapeutic likeness. We overcame these shortcomings through site-directed mutagenesis, the addition of a non-native disulfide bond, and the engineering of IL-37 as an Fc-fusion protein. Our results provide a platform for preclinical testing of IL-37 Fc-fusion proteins. The engineering approaches undertaken herein will apply to the conversion of similar potent yet short-acting cytokines into therapeutics.
Publisher: Elsevier BV
Date: 05-2019
Abstract: Produced by many cell types, macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with critical and supporting roles in many disease states and conditions. Its disease associations, myriad functions, receptors, and downstream signaling have been the subject of considerable research, yet many questions remain. Moreover, the relevance of MIF's partially functionally redundant family member, D-dopachrome tautomerase (D-DT), also remains to be further characterized. Here, we discuss recent discoveries demonstrating direct roles of MIF in supporting NLR Family Pyrin Domain-Containing 3 (NRLP3) inflammasome activation, as well as acting as a molecular chaperone for intracellular proteins. These findings may offer new clues to understanding MIF's multiple functions, and assist the development of putative MIF-targeting therapeutics for a variety of pathologies.
Publisher: Springer US
Date: 20-11-2020
DOI: 10.1007/978-1-4939-9936-1_13
Abstract: MIF has been described to be associated with autophagy in a number of studies, but the full nature of their association is not yet clear. However, the unprecedented interest in autophagy in recent times has generated a number of tools and techniques for its study. Here, we present protocols for studying the interactions between MIF and autophagy, including for the induction and inhibition of autophagy and measuring autophagosome biogenesis and maturation.
Publisher: Springer US
Date: 20-11-2020
DOI: 10.1007/978-1-4939-9936-1_10
Abstract: Immunoprecipitation is a technique which enables a macromolecule of interest to be isolated from heterogenous mixtures (particularly cell lysates). However, the immunoprecipitation of protein(s) can be challenging, with multiple variations of the basic technique required for successful antigenic pull-down. This depends on the target of interest, cell source, and localization. Here, immunoprecipitation of MIF from mouse and human macrophage cell lysates is described, which is both reliable and replicable, derived from multiple optimization experiments.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.MITO.2017.10.009
Abstract: Mitophagy is a selective form of autophagy in which damaged or dysfunctional mitochondria are specifically targeted by autophagosomes for lysosomal degradation. Studies have demonstrated that loss of autophagy/mitophagy can lead to a build-up of cytosolic reactive oxygen species and mitochondrial DNA, which can, in turn, activate immune signalling pathways that ultimately lead to the releases of inflammatory cytokines, including IL-1α, IL-1β, IL-18, type I IFN and macrophage migration inhibitory factor (MIF). Moreover, release of these cytokines can subsequently promote the release of others, including IL-23 and IL-17. Thus, as well as being essential for normal cell homeostasis and mitochondrial health, mitophagy may represent an important regulatory mechanism controlling inflammatory responses in immune cells. This review discusses our current understanding of the mechanisms through which mitophagy regulates inflammatory cytokine release.
Publisher: Springer US
Date: 20-11-2020
DOI: 10.1007/978-1-4939-9936-1_6
Abstract: Phenotyping cells by flow cytometry is a powerful way to identify cell type and any morphological changes during cell culture. The staining procedure used in this chapter enables the characterization of mouse macrophages by a flow cytometry antibody panel which can be used for both bone marrow-derived macrophages (BMM) and macrophages derived from other tissues, such as the mouse spleen or peritoneal cavity. The surface and intracellular staining methods are versatile and can be applied to flow cytometry staining of several different cell types by changing the surface markers used with knowledge of which receptors are expressed on different cell types.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Nadia Deen.