A F Lopez's research while affiliated with Monash University (Australia) and other places

... Identifying molecules that are differentially expressed in encepha litogenic T cells is critical to understanding how they mediate pathology, as well as identifying new and specific therapeutic targets for MS. IL3 is a molecule that is primarily produced by activated Tcells (5), but plays a critical role in the activation and survival of a diverse group of cells, includ ing mast cells and basophils, monocytes, B cells, T cells, and endothelial cells (6)(7)(8)(9)(10)(11)(12)(13). Studies have shown that IL3 contributes to inflammation and autoimmunity (14)(15)(16). ...

... Therefore, it is possible that phosphorylation of Ser-61, Ser-62, or Ser-64 induces a conformational change in the cytoplasmic domain of c-Mpl allowing other sites to undergo phosphorylation. In the human GM-CSF receptor ␤ subunit, it was recently reported that Ser-538 binds to 14-3-3 protein in vivo and in vitro (23). As the 14-3-3 molecule is known to bind to c-Raf and lead to MAPK activation, it is possible phosphorylated Ser residues in c-Mpl also bind to 14-3-3 proteins contributing to cellular proliferation and survival. ...

... Both have a favourable safety profile and are showing promising therapeutic benefit in small COVD-19 clinical trials [10,11], which support the advancement to larger clinical studies to clarify the significance of GM-CSF-dependent immunopathogenesis. An alternative strategy to blocking GM-CSF is to target the shared βc subunit, with the potential advantage of also blocking two other pro-inflammatory cytokines, IL-3 and IL-5 [12]. The role of type-2 immunity and IL-3 requires further investigation in severe COVID-19 patients, however there may be a pathogenic role for type-2 immunity at later stages of infection [13]. ...

... To generate the IL3RA-ADC BAY-943, a non-cell-permeable KSPi was conjugated randomly to the lysine residues of a humanized derivative of the anti-IL3RA antibody 7G3 [33], TPP-9476, via a novel protease-cleavable peptide linker [24]. IL3RA-ADC was efficacious in IL3RA-positive AML and HL cell lines in vitro, as well as in IL3RA-expressing AML and HL cell line and patient-derived xenograft (PDX) models in vivo. ...

... Initially based on the analysis of the biological activities of series of mutated forms of several cytokines (e.g., see [25][26][27][28][29]), and subsequently based on co-crystal structures of several cytokine/receptor pairs, including that for erythropoietin, GM-CSF and thrombopoietin and their receptors [30,31], two faces of the growth factor, one composed of its A and D helixes, and one of its A and C helixes, engage the two molecules of the homodimeric erythropoietin or thrombopoietin receptors, or the heterodimeric receptors for GM-CSF, IL-3 or IL-5 [31]. Moreover, these receptors appear to multimerize upon ligand binding, necessary for signal transduction [31]. ...

... [18][19][20] However, the glycosylation of GM-CSF is not required for its biological activity. [21,22] GM-CSF stimulates the development of neutrophils, macrophages, and dendritic cells. [23][24][25][26] Its medical importance lies in that this biopharmaceutical has been utilized in neutropenia treatments and, more recently, as an immune stimulant in tumor therapy and vaccine adjuvant in cancer patients. ...

... The search for immune mediators participating in the natural history of addiction has brought to place new actors such as Granulocyte colony-stimulating factor (G-CSF),a glycoprotein known by its hematopoietic functions 30 . As a neurotrophin, its main functions include the proliferation and differentiation of myeloid progenitors 30 , promoting the generation of granulocyte precursors and antiapoptotic actions 31,32 . G-CSF receptors were studied in the CNS due to their neuroprotective properties 33 including its anti-in ammatory effects found in dopaminergic neurons in the study of neurodegenerative disorders such as Parkinson's 34 and Alzheimer disease 35 . ...

... G-CSF has an impact on functional outcomes as determined mostly by in vitro studies. Here, G-CSF was shown to modulate programmed cell death mechanisms in neutrophils and in turn increases the life span in vitro (Begley et al., 1986;Colotta et al., 1992;Mooren et al., 2012). However, underlying mechanisms of the modulation of apoptosis are still not fully delineated but involve STAT, ERK and PI3K downstream signalling. ...