FASEB bioAdvances最新文献

{"title":"Fusion of the β2-adrenergic receptor with either Gαs or βarrestin-2 produces constitutive signaling by each pathway and induces gain-of-function in BEAS-2B cells","authors":"Emilio Y. Lucero-Garcia Rojas,&nbsp;Arfaxad Reyes-Alcaraz,&nbsp;Kehe Ruan,&nbsp;Bradley K. McConnell,&nbsp;Richard A. Bond","doi":"10.1096/fba.2022-00038","DOIUrl":"10.1096/fba.2022-00038","url":null,"abstract":"<p>The β₂AR is a prototypical G protein-coupled receptor (GPCR) known to orchestrate different cellular responses by the stimulation of specific signaling pathways. The best-established signaling pathways for the β₂AR are the canonical Gs pathway and the alternative β arrestin 2 (βarr2) pathway. Exploring each pathway separately remains a challenging task due to the dynamic nature of the receptor. Here, we fused the β₂AR with its cognate transducers, Gαs and βarr2, using short linkers as a novel approach for restricting the conformation of the receptor and preferentially activating one of its two signaling pathways. We characterized the behavior of our fusion proteins β₂AR-Gαs and β₂AR-βarr2 in HEK293 cells by measuring their constitutive activity, transducer recruitment, and pharmacological modulation. Our fusion proteins show (a) steric hindrance from the reciprocal endogenous transducers, (b) constitutive activity of the β₂AR for the signaling pathway activated by the tethered transducer, and (c) pharmacologic modulation by β₂AR ligands. Based on these characteristics, we further explored the possibility of a gain-of-function mechanism in the human lung non-tumorigenic epithelial cell line, BEAS-2B cells. This immortalized human bronchial epithelial cell line has immunomodulatory properties through cytokine release mediated by β₂AR stimulation. Our findings suggest that each signaling pathway of the β₂AR is biased toward either the Th1 or Th2 inflammatory response suggesting a role in regulating the immune phenotype of respiratory diseases. Our data imply that our fusion proteins can be used as tools to isolate the function elicited by a single signaling pathway in physiologically relevant cell types.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 12","pages":"758-774"},"PeriodicalIF":2.7,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/bb/FBA2-4-758.PMC9721090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of insulin-like growth factor 2 mRNA-binding protein 1 sensitizes colorectal cancer cells to chemotherapeutics","authors":"Nicole Betson,&nbsp;Mohammed Hajahmed,&nbsp;Tsige Gebretsadek,&nbsp;Kenneth Ndebele,&nbsp;H. Anwar Ahmad,&nbsp;Paul B. Tchounwou,&nbsp;Vladimir S. Spiegelman,&nbsp;Felicite K. Noubissi","doi":"10.1096/fba.2021-00069","DOIUrl":"10.1096/fba.2021-00069","url":null,"abstract":"<p>Although colorectal cancer (CRC) treatment has seen a remarkable improvement in the recent years, many patients will develop metastasis due to the resistance of cancer cells to chemotherapeutics. Targeting mechanisms driving the resistance of CRC cells to treatment would significantly reduce cases of metastasis and death. Induction of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a direct target of the Wnt/β-catenin signaling pathway, might promote resistance of CRC cells to treatment via activation of anti-apoptotic pathways and induction of the multidrug resistance (MDR1) membrane transporter that pumps drugs out of the cells. We hypothesized that inhibition of IGF2BP1 will sensitize CRC cells to chemotherapeutics. We used CRC cell lines with different status of activation of Wnt signaling to show that inhibition of IGF2BP1 potentiates the anti-growth and anti-proliferative effects of chemotherapeutics on CRC cells with activated Wnt/β-catenin signaling pathway. We observed that the inhibition of IGF2BP1 significantly increases apoptosis in the same cells. A remarkable reduction in the migratory capability of those cells was noted as well. We found that inhibition of IGF2BP1 is sufficient to decrease the resistance of chemotherapy-resistant cancer cells with activated Wnt/β-catenin signaling pathway. These findings portray IGF2BP1 as a good candidate for CRC therapy.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 12","pages":"816-829"},"PeriodicalIF":2.7,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/06/FBA2-4-816.PMC9721091.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transgenic overexpression of α7 integrin in smooth muscle attenuates allergen-induced airway inflammation in a murine model of asthma","authors":"Mariam A. Ba,&nbsp;Annemarie Aiyuk,&nbsp;Karla Hernández,&nbsp;Jon M. Evasovic,&nbsp;Ryan D. Wuebbles,&nbsp;Dean J. Burkin,&nbsp;Cherie A. Singer","doi":"10.1096/fba.2022-00050","DOIUrl":"10.1096/fba.2022-00050","url":null,"abstract":"<p>Asthma is a chronic inflammatory disorder of the lower airways characterized by modulation of airway smooth muscle (ASM) function. Infiltration of smooth muscle by inflammatory mediators is partially regulated by transmembrane integrins and the major smooth muscle laminin receptor α7β1 integrin plays a critical role in the maintenance of ASM phenotype. The goal of the current study was to investigate the role of α7 integrin in asthma using smooth muscle-specific α7 integrin transgenic mice (TgSM-Itgα7) using both acute and chronic OVA sensitization and challenge protocols that mimic mild to severe asthmatic phenotypes. Transgenic over-expression of the α7 integrin in smooth muscle resulted in a significant decrease in airway resistance relative to controls, reduced the total number of inflammatory cells and substantially inhibited the production of crucial Th2 and Th17 cytokines in airways. This was accompanied by decreased secretion of various inflammatory chemokines such as eotaxin/CCL11, KC/CXCL3, MCP-1/CCL2, and MIP-1β/CCL4. Additionally, α7 integrin overexpression significantly decreased ERK1/2 phosphorylation in the lungs of TgSM-Itgα7 mice and affected proliferative, contractile, and inflammatory downstream effectors of ERK1/2 that drive smooth muscle phenotype in the lung. Taken together, these results support the hypothesis that enhanced expression of α7 integrin in vivo inhibits allergic inflammation and airway resistance. Moreover, we identify ERK1/2 as a potential target by which α7 integrin signals to regulate airway inflammation. We conclude that identification of therapeutics targeting an increase in smooth muscle α7 integrin expression could serve as a potential novel treatment for asthma.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 11","pages":"724-740"},"PeriodicalIF":2.7,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/57/FBA2-4-724.PMC9635010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multienzyme activity profiling for evaluation of cell-to-cell variability of metabolic state","authors":"Govind S. Gill,&nbsp;Michael C. Schultz","doi":"10.1096/fba.2022-00073","DOIUrl":"10.1096/fba.2022-00073","url":null,"abstract":"<p>In solid organs, cells of the same “type” can vary in their molecular phenotype. The basis of this state variation is being revealed by characterizing cell features including the expression pattern of mRNAs and the internal distribution of proteins. Here, the variability of metabolic state between cells is probed by enzyme activity profiling. We study individual cells of types that can be identified during the post-mitotic phase of oogenesis in Xenopus laevis. Whole-cell homogenates of isolated oocytes are used for kinetic analysis of enzymes, with a focus on the initial reaction rate. For each oocyte type studied, the activity signatures of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and malate dehydrogenase 1 (MDH1) vary more between the homogenates of single oocytes than between repeat samplings of control homogenates. Unexpectedly, the activity signatures of GAPDH and MDH1 strongly co-vary between oocytes of each type and change in strength of correlation during oogenesis. Therefore, variability of the kinetic behavior of these housekeeping enzymes between “identical” cells is physiologically programmed. Based on these findings, we propose that single-cell profiling of enzyme kinetics will improve understanding of how metabolic state heterogeneity is related to heterogeneity revealed by omics methods including proteomics, epigenomics, and metabolomics.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 11","pages":"709-723"},"PeriodicalIF":2.7,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/e3/FBA2-4-709.PMC9635011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional brain activation during rectal distention and attenuation with alosetron in a nonhuman primate model of irritable bowel syndrome","authors":"Rintaro Fujii,&nbsp;Yuji Awaga,&nbsp;Kenya Nozawa,&nbsp;Mayumi Matsushita,&nbsp;Aldric Hama,&nbsp;Takahiro Natsume,&nbsp;Hiroyuki Takamatsu","doi":"10.1096/fba.2022-00048","DOIUrl":"10.1096/fba.2022-00048","url":null,"abstract":"<p>Greater understanding of the mechanism that mediates visceral pain and hypersensitivity associated with irritable bowel syndrome (IBS) would facilitate the development of effective therapeutics to manage these symptoms. An objective marker associated with the underlying mechanisms of visceral pain and hypersensitivity could be used to guide therapeutic development. The current study examined brain activation evoked by rectal distention with functional magnetic resonance imaging (fMRI) in a cynomolgus macaque model of visceral hypersensitivity. Male, cynomolgus macaques underwent five four-week treatments of dextran sodium sulfate (DSS)-distilled water (DW), which induced mild–moderate colitis with remission during each treatment cycle. Balloon rectal distention (RD) was performed under anesthesia 14 weeks after the final DSS-DW treatment. Colonoscopy confirmed the absence of colitis prior to the start of RD. In naïve, untreated macaques, 10, 20 and 30 ml RD did not evoke brain activation. However, insular cortex/somatosensory II cortex and cerebellum were significantly activated in DSS-treated macaques at 20 and 30 ml rectal distention. Intra-rectal pressure after DSS treatment was not significantly different from that of naïve, untreated macaques, indicating lack of alteration of rectal functioning following DSS-treatment. Treatment with 5-HT₃ receptor antagonist alosetron (p.o.) reduced distension-evoked brain activation and decreased intra-rectal pressure. The current findings demonstrated activation of brain regions to RD following DSS treatments which was not present in naïve macaques, suggesting visceral hypersensitivity. Brain activation in turn was reduced by alosetron, which could underlie the analgesic effect alosetron in IBS patients.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 11","pages":"694-708"},"PeriodicalIF":2.7,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/c9/FBA2-4-694.PMC9635009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40673516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential modulation of cancer-related genes by mitochondrial DNA haplogroups and the STING DNA sensing system","authors":"Kevin Schneider,&nbsp;Marilyn Chwa,&nbsp;Shari R. Atilano,&nbsp;Sonali Nashine,&nbsp;Nitin Udar,&nbsp;David S. Boyer,&nbsp;S. Michal Jazwinski,&nbsp;Michael V. Miceli,&nbsp;Anthony B. Nesburn,&nbsp;Baruch D. Kuppermann,&nbsp;M. Cristina Kenney","doi":"10.1096/fba.2019-00044","DOIUrl":"10.1096/fba.2019-00044","url":null,"abstract":"<p>Activation of the Simulator of Interferon Genes (STING) system by mitochondrial (mt) DNA can upregulate type 1 interferon genes and enhance immune responses to combat bacterial and viral infections. In cancers, the tumor-derived DNA activates STING leading to upregulation of IFN-beta and induction of antitumor T cells. The entire mtDNA from the cell lines was sequenced using next-generation sequencing (NGS) technology with independent sequencing of both strands in both directions, allowing identification of low-frequency heteroplasmy SNPs. There were 15 heteroplasmy SNPs showing a range from 3.4% to 40.5% occurrence in the K cybrid cell lines. Three H haplogroup cybrids possessed SNP heteroplasmy that ranged from 4.39% to 30.7%. The present study used qRT-PCR to determine if cybrids of H and K haplogroups differentially regulate expression levels of five cancer genes (<i>BRAC1</i>, <i>ALK</i>, <i>PD1, EGFR</i>, and <i>HER2</i>) and seven STING subunits genes (<i>CGAS</i>, <i>TBK1</i>, <i>IRF3</i>, <i>IκBa</i>, <i>NFκB</i>, <i>TRAF2</i>, and <i>TNFRSF19</i>). Some cybrids underwent siRNA knockdown of STING followed by qRT-PCR in order to determine the impact of STING on gene expression. Rho<i>0</i> (lacking mtDNA) ARPE-19 cells were used to determine if mtDNA is required for the expression of the cancer genes studied. Our results showed that (a) K cybrids have lower expression levels for <i>BRAC1</i>, <i>ALK</i>, <i>PD1, EGFR, IRF3</i>, and <i>TNFRSF19</i> genes but increased transcription for <i>IκBa</i> and <i>NFκB</i> compared to H cybrids; (b) STING KD decreases expression of <i>EGFR</i> in both H and K cybrids, and (c) <i>PD1</i> expression is negligible in Rho<i>0</i> cells. Our findings suggest that the STING DNA sensing pathway may be a previously unrecognized pathway to target modulation of cancer-related genes and the <i>PD1</i> expression requires the presence of mtDNA.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 10","pages":"675-689"},"PeriodicalIF":2.7,"publicationDate":"2022-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/83/FBA2-4-675.PMC9536090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9343085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1111/phc3.12678","DOIUrl":"https://doi.org/10.1111/phc3.12678","url":null,"abstract":"","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44281999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme Detoxification Protein (PfHDP) is essential for the hemoglobin uptake and metabolism in Plasmodium falciparum","authors":"Priya Gupta,&nbsp;Rajan Pandey,&nbsp;Vandana Thakur,&nbsp;Sadaf Parveen,&nbsp;Inderjeet Kaur,&nbsp;Ashutosh Panda,&nbsp;Rashmita Bishi,&nbsp;Sonali Mehrotra,&nbsp;Asif Akhtar,&nbsp;Dinesh Gupta,&nbsp;Asif Mohmmed,&nbsp;Pawan Malhotra","doi":"10.1096/fba.2022-00021","DOIUrl":"10.1096/fba.2022-00021","url":null,"abstract":"<p>Hemoglobin degradation is crucial for the growth and survival of <i>Plasmodium falciparum</i> in human erythrocytes. Although the process of Hb degradation has been studied in detail, the mechanisms of Hb uptake remain ambiguous to date. Here, we characterized Heme Detoxification Protein (<i>Pf</i>HDP); a protein localized in the parasitophorus vacuole, parasite food vacuole, and infected erythrocyte cytosol for its role in Hb uptake. Immunoprecipitation of <i>Pf</i>HDP-GFP fusion protein from a transgenic line using GFP trap beads showed the association of <i>Pf</i>HDP with Hb as well as with the members of PTEX translocon complex. Association of <i>Pf</i>HDP with Hb or <i>Pf</i>exp-2, a component of translocon complex was confirmed by protein–protein interaction and immunolocalization tools. Based on these associations, we studied the role of <i>Pf</i>HDP in Hb uptake using the <i>Pf</i>HDP-HA-GlmS transgenic parasites line. <i>Pf</i>HDP knockdown significantly reduced the Hb uptake in these transgenic parasites in comparison to the wild-type parasites. Morphological analysis of <i>Pf</i>HDP-HA-GlmS transgenic parasites in the presence of GlcN showed food vacuole abnormalities and parasite stress, thereby causing a growth defect in the development of these parasites. Transient knockdown of a member of translocon complex, <i>Pf</i>HSP101 in HSP101-DDDHA parasites also showed a decreased uptake of Hb inside the parasite. Together, these results advocate an interaction between <i>Pf</i>HDP and the translocon complex at the parasitophorus vacuole membrane and also suggest a role for <i>Pf</i>HDP in the uptake of Hb and parasite development. The study thus reveals new insights into the function of <i>Pf</i>HDP, making it an extremely important target for developing new antimalarials.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 10","pages":"662-674"},"PeriodicalIF":2.7,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/9a/FBA2-4-662.PMC9536087.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33538256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FVB/N mouse strain regulatory T cells differ in phenotype and function from the C57BL/6 and BALB/C strains","authors":"Scott M. Tanner,&nbsp;Robin G. Lorenz","doi":"10.1096/fba.2021-00161","DOIUrl":"10.1096/fba.2021-00161","url":null,"abstract":"<p>Regulatory T cells (Treg) are vital to the maintenance of immune homeostasis. The genetic background of an inbred mouse strain can have a profound effect on the immune response in the animal, including Treg responses. Most Treg studies focus on animals created on the C57BL/6 or BALB/c background. Recent studies have demonstrated a difference in the phenotype and behavior of C57BL/6 and BALB/c Tregs. In this study, we have investigated the function of FVB/N Tregs compared to C57BL/6 and BALB/c. We observed that while FVB/N Tregs appear to suppress normally in a cell contact-dependent system, FVB/N Tregs are less capable of suppressing when regulation depends on the secretion of a soluble factor. FVB/N Tregs produce IL-10; however, TGF-β was not detected in any culture from C57BL/6 or FVB/N. C57BL/6 Foxp3⁺ Tregs expressed more of the TGF-β-related proteins glycoprotein-A repetitions predominant (GARP) and latency-associated peptide (LAP) on the cell surface than both FVB/N and BALB/c, but C57BL/6 Tregs expressed significantly less <i>Ctse</i> (Cathepsin E) mRNA. Each strain displayed different abilities of thymic Tregs (tTreg) to maintain Foxp3 expression and had a varying generation of induced Tregs (iTregs). In vitro generated FVB/N iTregs expressed significantly less GARP and LAP. These results suggest Tregs of different strains have varying phenotypes and dominant mechanisms of action for the suppression of an immune response. This information should be taken into consideration when Tregs are examined in future studies, particularly for therapeutic purposes in a genetically diverse population.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 10","pages":"648-661"},"PeriodicalIF":2.7,"publicationDate":"2022-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/99/FBA2-4-648.PMC9536134.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33538253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Q & A with FASEB BioAdvances Editors-in-Chief","authors":"Crislyn D'Souza-Schorey,&nbsp;Yung Hou Wong,&nbsp;Jeannine Botos,&nbsp;Darla P. Henderson","doi":"10.1096/fba.2022-00064","DOIUrl":"https://doi.org/10.1096/fba.2022-00064","url":null,"abstract":"&lt;p&gt;Yung (Figure 1, right): I received my doctoral degree in Pharmacology from the University of Cambridge and conducted postdoctoral training at the University of California San Francisco. Since the early 1990s, I have established my own research laboratory at the Hong Kong University of Science and Technology. As a molecular pharmacologist, my research interests are primarily focused on the delineation of signaling mechanisms regulated by the G protein-coupled receptors (GPCRs). I have examined the G protein-coupling specificities and effector systems of GPCRs for opioid peptides, melatonin, and chemokines, and explored how these and other GPCRs regulate gene transcription and cell proliferation and differentiation.&lt;/p&gt;&lt;p&gt;Crislyn (Figure 1, left): My research interests lie at the intersection of two exciting areas of biomedical research—Cell Biology and Molecular Oncology. We examine the cellular changes that accompany the early stages of tumor progression. A current line of investigation in my laboratory is to understand the biogenesis and paracrine properties of extracellular vesicles in the tumor microenvironment. For my doctoral studies and then postdoctoral research, I had the privilege of training and working with two outstanding scientists, both statesmen in their fields. Their labs provided environments that not only consolidated my enthusiasm for research but also tendered a vision for mentoring and leading. I joined the faculty at the University of Notre Dame in the late 1990s, where I established my independent research program.&lt;/p&gt;&lt;p&gt;Crislyn: The FASEB organization is well recognized in the biological and biomedical science communities as the largest US biomedical coalition, representing 28 societies and well over 100,000 researchers. I recollect learning about FASEB's high repute as a graduate student. So, in 2020, I gladly accepted the invitation to serve as Associate Editor of their newly launched open-access journal, &lt;i&gt;FASEB BioAdvances&lt;/i&gt;. I am an advocate of open-access publishing and the broad and inclusive reach it engenders. Open-access publishing can transform scientific discourse by taking full advantage of the online platform. I was honored to be nominated and the selected as Editor-in-Chief by the search committee. It is a tremendous opportunity to serve the broader scientific community.&lt;/p&gt;&lt;p&gt;Yung: Modern-day science has become increasingly multidisciplinary in nature, and this is especially true in biological and biomedical research. Seminal discoveries through interdisciplinary research will undoubtedly be needed to address complex biomedical challenges of the 21st century. &lt;i&gt;FASEB BioAdvances&lt;/i&gt; provides a unique publication platform for the rapid dissemination of high-quality research papers with a wide coverage. As an Editor-in-Chief of &lt;i&gt;FASEB BioAdvances&lt;/i&gt;, I will have the privilege to read exciting scientific discoveries and advancements contributed by colleagues around the world. Additionally, I will hav","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"4 8","pages":"506-508"},"PeriodicalIF":2.7,"publicationDate":"2022-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2022-00064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92299269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}