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  1. Boyle ST, Mittal P, Kaur G, Hoffmann P, Samuel MS, Klingler-Hoffmann M
    J Proteome Res, 2020 10 02;19(10):4093-4103.
    PMID: 32870688 DOI: 10.1021/acs.jproteome.0c00511
    Tumorigenesis involves a complex interplay between genetically modified cancer cells and their adjacent normal tissue, the stroma. We used an established breast cancer mouse model to investigate this inter-relationship. Conditional activation of Rho-associated protein kinase (ROCK) in a model of mammary tumorigenesis enhances tumor growth and progression by educating the stroma and enhancing the production and remodeling of the extracellular matrix. We used peptide matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify the proteomic changes occurring within tumors and their stroma in their regular spatial context. Peptides were ranked according to their ability to discriminate between the two groups, using a receiver operating characteristic tool. Peptides were identified by liquid chromatography tandem mass spectrometry, and protein expression was validated by quantitative immunofluorescence using an independent set of tumor samples. We have identified and validated four key proteins upregulated in ROCK-activated mammary tumors relative to those expressing kinase-dead ROCK, namely, collagen I, α-SMA, Rab14, and tubulin-β4. Rab14 and tubulin-β4 are expressed within tumor cells, whereas collagen I is localized within the stroma. α-SMA is predominantly localized within the stroma but is also expressed at higher levels in the epithelia of ROCK-activated tumors. High expression of COL1A, the gene encoding the pro-α 1 chain of collagen, correlates with cancer progression in two human breast cancer genomic data sets, and high expression of COL1A and ACTA2 (the gene encoding α-SMA) are associated with a low survival probability (COLIA, p = 0.00013; ACTA2, p = 0.0076) in estrogen receptor-negative breast cancer patients. To investigate whether ROCK-activated tumor cells cause stromal cancer-associated fibroblasts (CAFs) to upregulate expression of collagen I and α-SMA, we treated CAFs with medium conditioned by primary mammary tumor cells in which ROCK had been activated. This led to abundant production of both proteins in CAFs, clearly highlighting the inter-relationship between tumor cells and CAFs and identifying CAFs as the potential source of high levels of collagen 1 and α-SMA and associated enhancement of tissue stiffness. Our research emphasizes the capacity of MALDI-MSI to quantitatively assess tumor-stroma inter-relationships and to identify potential prognostic factors for cancer progression in human patients, using sophisticated mouse cancer models.
  2. Singh R, Samuel MS, Ravikumar M, Ethiraj S, Kirankumar VS, Kumar M, et al.
    Chemosphere, 2023 Dec;344:140311.
    PMID: 37769916 DOI: 10.1016/j.chemosphere.2023.140311
    The carbon dioxide (CO2) crisis is one of the world's most urgent issues. Meeting the worldwide targets set for CO2 capture and storage (CCS) is crucial. Because it may significantly reduce energy consumption compared to traditional amine-based adsorption capture, adsorption dependant CO2 capture is regarded as one of the most hopeful techniques in this paradigm. The expansion of unique, critical edge adsorbent materials has received most of the research attention to date, with the main objective of improving adsorption capacity and lifespan while lowering the temperature of adsorption, thereby lowering the energy demand of sorbent revival. There are specific materials needed for each step of the carbon cycle, including capture, regeneration, and conversion. The potential and efficiency of metal-organic frameworks (MOFs) in overcoming this obstacle have recently been proven through research. In this study, we pinpoint MOFs' precise structural and chemical characteristics that have contributed to their high capture capacity, effective regeneration and separation processes, and efficient catalytic conversions. As prospective materials for the next generation of energy storage and conversion applications, carbon-based compounds like graphene, carbon nanotubes, and fullerenes are receiving a lot of interest. Their distinctive physicochemical characteristics make them suitable for these popular study topics, including structural stability and flexibility, high porosity, and customizable physicochemical traits. It is possible to precisely design the interior of MOFs to include coordinatively unsaturated metal sites, certain heteroatoms, covalent functionalization, various building unit interactions, and integrated nanoscale metal catalysts. This is essential for the creation of MOFs with improved performance. Utilizing the accuracy of MOF chemistry, more complicated materials must be built to handle selectivity, capacity, and conversion all at once to achieve a comprehensive solution. This review summarizes, the most recent developments in adsorption-based CO2 combustion capture, the CO2 adsorption capacities of various classes of solid sorbents, and the significance of advanced carbon nanomaterials for environmental remediation and energy conversion. This review also addresses the difficulties and potential of developing carbon-based electrodes for energy conversion and storage applications.
  3. Samuel MS, Rath N, Masre SF, Boyle ST, Greenhalgh DA, Kochetkova M, et al.
    Genesis, 2016 Dec;54(12):636-646.
    PMID: 27775859 DOI: 10.1002/dvg.22988
    The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER). This two-stage system of regulation allows for tissue-selective expression of the ROCK2:ER fusion protein, which then requires administration of estrogen analogues such as tamoxifen or 4-hydroxytamoxifen to elicit kinase activity. This conditional gain-of-function system was validated in multiple tissues by crossing with mice expressing CRE recombinase under the transcriptional control of cytokeratin14 (K14), murine mammary tumor virus (MMTV) or cytochrome P450 Cyp1A1 (Ah) promoters, driving appropriate expression in the epidermis, mammary or intestinal epithelia respectively. Given the interest in ROCK signaling in normal physiology and disease, this mouse line will facilitate research into the consequences of ROCK activation that could be used to complement conditional knockout models. Birth Defects Research (Part A) 106:636-646, 2016. © 2016 Wiley Periodicals, Inc.
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